bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis
Authors: Quaranta Pamela , Basso-Ricci Luca , Jofra Hernandez Raisa , Pacini Guido , Naldini Matteo Maria , Barcella Matteo , Seffin Luca , Pais Giulia , Spinozzi Giulio , Benedicenti Fabrizio , Pietrasanta Carlo , Cheong Jin Gyu , Ronchi Andrea , Pugni Lorenza , Dionisio Francesca , Monti Ilaria , Giannelli Stefania , Darin Silvia , Fraschetta Federico , Barera Graziano , Ferrua Francesca , Calbi Valeria , Ometti Marco , Di Micco Raffaella , Mosca Fabio , Josefowicz Steven Zvi , Montini Eugenio , Calabria Andrea , Bernardo Maria Ester , Cicalese Maria Pia , Gentner Bernhard , Merelli Ivan , Aiuti Alessandro , Scala Serena 
Published: March 2024

AbstractIn physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single-cell transcriptional and functional profiling, and integration site (IS) clonal tracking, we unveiled the biological properties and the transcriptional features of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPCs reduced in cell count over aging and are enriched for primitive, lymphoid, and erythroid subpopulations, showing preactivated transcriptional and functional state. Moreover, cHSPCs have low expression of multiple BM-retention molecules but maintain their homing potential after xenotransplantation. By generating a comprehensive human organ-resident HSPC data set based on single-cell RNA sequencing data, we detected organ-specific seeding properties of the distinct trafficking HSPC subpopulations. Notably, circulating multi-lymphoid progenitors are primed for seeding the thymus and actively contribute to T-cell production. Human clonal tracking data from patients receiving gene therapy (GT) also showed that cHSPCs connect distant BM niches and participate in steady-state hematopoietic production, with primitive cHSPCs having the highest recirculation capability to travel in and out of the BM. Finally, in case of hematopoietic impairment, cHSPCs composition reflects the BM-HSPC content and might represent a biomarker of the BM state for clinical and research purposes. Overall, our comprehensive work unveiled fundamental insights into the in vivo dynamics of human HSPC trafficking and its role in sustaining hematopoietic homeostasis. GT patients’ clinical trials were registered at ClinicalTrials.gov (NCT01515462 and NCT03837483) and EudraCT (2009-017346-32 and 2018-003842-18).
Alloengraftment without significant toxicity or GVHD in CD45 antibody-drug conjugate–conditioned Fanconi anemia mice
Authors: Saha Asim , Palchaudhuri Rahul , Lanieri Leanne , Hyzy Sharon , Riddle Megan J. , Panthera Jamie , Eide Cindy R. , Tolar Jakub , Panoskaltsis-Mortari Angela , Gorfinkel Lev , Tkachev Victor , Gerdemann Ulrike , Alvarez-Calderon Francesca , Palato Elisa Rojas , MacMillan Margaret L. , Wagner John E. , Kean Leslie S. , Osborn Mark J. , Kiem Hans-Peter , Scadden David T. , Olson Lisa M. , Blazar Bruce R. 
Published: March 2024

Abstract
Fanconi anemia (FA) is an inherited DNA repair disorder characterized by bone marrow (BM) failure, developmental abnormalities, myelodysplasia, leukemia, and solid tumor predisposition. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a mainstay treatment, is limited by conditioning regimen–related toxicity and graft-versus-host disease (GVHD). Antibody-drug conjugates (ADCs) targeting hematopoietic stem cells (HSCs) can open marrow niches permitting donor stem cell alloengraftment. Here, we report that single dose anti-mouse CD45–targeted ADC (CD45-ADC) facilitated stable, multilineage chimerism in 3 distinct FA mouse models representing 90% of FA complementation groups. CD45-ADC profoundly depleted host stem cell enriched Lineage−Sca1+cKit+ cells within 48 hours. Fanca−/− recipients of minor-mismatched BM and single dose CD45-ADC had peripheral blood (PB) mean donor chimerism &gt;90%; donor HSCs alloengraftment was verified in secondary recipients. In Fancc−/− and Fancg−/− recipients of fully allogeneic grafts, PB mean donor chimerism was 60% to 80% and 70% to 80%, respectively. The mean percent donor chimerism in BM and spleen mirrored PB results. CD45-ADC–conditioned mice did not have clinical toxicity. A transient &lt;2.5-fold increase in hepatocellular enzymes and mild-to-moderate histopathological changes were seen. Under GVHD allo-HSCT conditions, wild-type and Fanca−/− recipients of CD45-ADC had markedly reduced GVHD lethality compared with lethal irradiation. Moreover, single dose anti–human CD45-ADC given to rhesus macaque nonhuman primates on days −6 or −10 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable patients with FA.
Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1
Authors: Guo Hengru , Xin Ying , Wang Saifei , Zhang Xiaoning , Ren Yanqi , Qiao Bo , Li Hongjiang , Wu Jing , Hao Xiao , Xu Lijun , Yan Yushan , Zhang Haohao 
Published: March 2024

Abstract
Background
Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear.

Methods
The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells.

Results
POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance.

Conclusion
Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.
One-year prevalence of cluster headache, hemicrania continua, paroxysmal hemicrania and SUNCT in Norway: a population-based nationwide registry study
Authors: Hagen Knut 
Published: March 2024

Abstract
Background
There is lack of population-based studies evaluating the prevalence of paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks.

Objectives
The aim of this study was to investigate the gender-specific 1-year prevalence of cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks.

Methods
A nationwide study was conducted from January 1 2022 and December 31 2022 by linking diagnostic codes from Norwegian Patient Registry and prescription of relevant drugs from Norwegian Prescription Database on an individual basis. The 1-year prevalence with 95% confidence intervals (CI) of cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks are estimated based on the combination of diagnostic codes, prescription of drugs and corresponding reimbursement codes.

Results
Among 4,316,747 individuals aged ≥ 18 years, the 1-year prevalence per 100,000 was 14.6 (95% CI 13.5–15.8) for cluster headache, 2.2 (95% CI 1.8–2.7) for hemicrania continua, 1.4 (95% CI 1.0–1.8) for paroxysmal hemicrania, and 1.2 (95% CI 0.8–1.4) for short-lasting unilateral neuralgiform headache attacks. For all the trigeminal autonomic cephalalgies, cluster headache included, the prevalence was higher for women than men.

Conclusions
In this nationwide register-based study, we found a 1-year prevalence per 100,100 of 14.6 for cluster headache, 2.2 for hemicranias continua, 1.4 for paroxysmal hemicranias, and 1.2 for short-lasting unilateral neuralgiform headache attacks. This is the first study reporting higher prevalence of cluster headache for women than men.
High pesticide tolerance of S. mansoni: implications for the risk of schistosomiasis
Authors: Ganatra Akbar A. , McOdimba Francis , Kaneno Salim , Becker Jeremias M. , Shahid Naeem , Hollert Henner , Liess Matthias , Agola Eric L. , Fillinger Ulrike 
Published: March 2024

Abstract
Background
Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma. The pathogen is transmitted via freshwater snails. These snails are highly tolerant to agricultural pesticides and indirectly benefit from exposure due to adverse effects on their more sensitive enemy species. Pesticides in surface waters may thus increase the risk of schistosomiasis transmission unless they also affect the pathogen. We tested the tolerance of the free-swimming life stages (miracidia and cercariae) of Schistosoma mansoni to the insecticides diazinon and imidacloprid. We also investigated whether these pesticides decrease the ability of miracidia to infect and further develop as sporocysts within the host snail Biomphalaria pfeifferi.

Results
Exposure to imidacloprid for 6 and 12 h immobilized 50% of miracidia at 150 and 16 µg/L, respectively (nominal EC50); 50% of cercariae were immobilized at 403 and 284 µg/L. Diazinon immobilized 50% of miracidia at 51 and 21 µg/L after 6 and 12 h; 50% of cercariae were immobilized at 25 and 13 µg/L. The observed insecticide tolerance is lower than those of the host snail B. pfeifferi and comparable to those of other commonly tested freshwater invertebrates. Exposure for up to 6 h decreased the infectivity of miracidia at high sublethal concentrations (48.8 µg imidacloprid/L and 10.5 µg diazinon/L, i.e. 20–33% of EC50), but not at lower concentrations commonly observed in the field (4.88 µg imidacloprid/L and 1.05 µg diazinon/L). The development of sporocysts within the snail host was not affected at any of these test concentrations.

Conclusions
Insecticides did not affect the performance of S. mansoni at environmentally relevant concentrations. Particularly within its host snail the pathogen can escape exposure peaks that have been shown to affect other sensitive invertebrates and their biological control of host snails. Our findings suggest that freshwater pollution with agricultural pesticides increases the risk of schistosomiasis; they illustrate the need to integrate an environmental and public health risk assessment and management.
Accumulation mechanism of metabolite markers identified by machine learning between Qingyuan and Xiushui counties in Polygonatum cyrtonema Hua
Authors: Gong Qiqi , Yu Jianfeng , Guo Zhicheng , Fu Ke , Xu Yi , Zou Hui , Li Cong , Si Jinping , Cai Shengguan , Chen Donghong , Han Zhigang 
Published: March 2024

AbstractPolygonatum cyrtonema Hua is a traditional Chinese medicinal plant acclaimed for its therapeutic potential in diabetes and various chronic diseases. Its rhizomes are the main functional parts rich in secondary metabolites, such as flavonoids and saponins. But their quality varies by region, posing challenges for industrial and medicinal application of P. cyrtonema. In this study, 482 metabolites were identified in P. cyrtonema rhizome from Qingyuan and Xiushui counties. Cluster analysis showed that samples between these two regions had distinct secondary metabolite profiles. Machine learning methods, specifically support vector machine-recursive feature elimination and random forest, were utilized to further identify metabolite markers including flavonoids, phenolic acids, and lignans. Comparative transcriptomics and weighted gene co-expression analysis were performed to uncover potential candidate genes including CHI, UGT1, and PcOMT10/11/12/13 associated with these compounds. Functional assays using tobacco transient expression system revealed that PcOMT10/11/12/13 indeed impacted metabolic fluxes of the phenylpropanoid pathway and phenylpropanoid-related metabolites such as chrysoeriol-6,8-di-C-glucoside, syringaresinol-4'-O-glucopyranosid, and 1-O-Sinapoyl-D-glucose. These findings identified metabolite markers between these two regions and provided valuable genetic insights for engineering the biosynthesis of these compounds.
Sciatica caused by spinal epidural abscess as the initial clinical presentation of colon cancer: a rare case report and review of literature
Authors: Lu Kuan-Yu , Tung Wei-En , Chiang Chang-Jung , Hsieh Yueh-Ying , Chen Chia-Hsien , Lee Mei-Hui , Yen Min-Hsuan , Lu Po-Wen , Wu Lien-Chen 
Published: March 2024

Abstract
Background
Colorectal cancer is one of the most frequently diagnosed forms of cancer, and it is associated with several common symptoms and signs such as rectal bleeding, altered bowel habits, abdominal pain, anemia, and unintentional weight loss. Sciatica, a debilitating condition in which the patient experiences paresthesia and pain in the dermatome of associated lumbosacral nerve roots or sciatic nerve distribution, is not considered one of these. Here we present a case of colorectal cancer manifesting symptoms of sciatica alone.

Case presentation
A 68-year-old male presented with progressive lower back pain radiating to his left thigh and calf over L5/S1 dermatome. Sciatica was suspected and initially underwent conservative treatment with analgesics. However, the symptoms progressed and MRI revealed an epidural abscess surprisingly. Surgical debridement was performed and pus culture isolated Streptococcus gallolyticus. Based on the strong association of S. gallolyticus with colorectal cancer, the presence of this pathogen prompted further tumor evaluation, even in the absence of the typical symptoms and signs. This investigation ultimately leads to the diagnosis of sigmoid adenocarcinoma.

Conclusions
Although rare, sciatica caused by S. gallolyticus infection of the spinal epidural space may serve as the initial presentation of colorectal cancer. Physicians should be aware of the strong association between S. gallolyticus and colorectal cancer. Based on what we currently know about the condition; a thorough systematic assessment of occult neoplasia for patients with S. gallolyticus infection is recommended.
Diverse proinflammatory response in pharyngeal epithelial cells upon interaction with Neisseria meningitidis carriage and invasive isolates
Authors: Persson Alexander , Koivula Therese , Jacobsson Susanne , Stenmark Bianca 
Published: March 2024

Abstract
Background
Invasive meningococcal disease (IMD), including sepsis and meningitis, can develop when Neisseria meningitidis bacteria breach the barrier and gain access to the circulation. While IMD is a rare outcome of bacterial exposure, colonization of the oropharynx is present in approximately 10% of the human population. This asymptomatic carriage can be long or short term, and it is unknown which determining factors regulate bacterial colonization. Despite descriptions of many bacterial virulence factors and recent advances in detailed genetic identification and characterization of bacteria, the factors mediating invasion and disease vs. asymptomatic carriage following bacterial colonization remain unknown. The pharyngeal epithelia play a role in the innate immune defense against pathogens, and the aim of this study was to investigate the proinflammatory response of pharyngeal epithelial cells following meningococcal exposure to describe the potential inflammatory mediation performed during the initial host‒pathogen interaction. Clinically relevant isolates of serogroups B, C, W and Y, derived from patients with meningococcal disease as well as asymptomatic carriers, were included in the study.

Results
The most potent cellular response with proinflammatory secretion of TNF, IL-6, CXCL8, CCL2, IL-1β and IL-18 was found in response to invasive serogroup B isolates. This potent response pattern was also mirrored by increased bacterial adhesion to cells as well as induced cell death. It was, however, only with serogroup B isolates where the most potent cellular response was toward the IMD isolates. In contrast, the most potent cellular response using serogroup Y isolates was directed toward the carriage isolates rather than the IMD isolates. In addition, by comparing isolates from outbreaks in Sweden (epidemiologically linked and highly genetically similar), we found the most potent proinflammatory response in cells exposed to carriage isolates rather than the IMD isolates.

Conclusion
Although certain expected correlations between host‒pathogen interactions and cellular proinflammatory responses were found using IMD serogroup B isolates, our data indicate that carriage isolates invoke stronger proinflammatory activation of the epithelial lining than IMD isolates.
The effects of dietary diversity on health status among the older adults: an empirical study from China
Authors: Zhu Yali , An Qiaozhen , Rao Jiahao 
Published: March 2024

Abstract
Background
Dietary diversity is an indicator of nutrient intake among the elderly. Previous researches have primarily examined dietary diversity and the risks with chronic and infectious disease and cognitive impairment, limited evidence shows the association between dietary diversity and the overall health status of specific populations with a heterogeneity analysis. This study aimed to probe the effects of dietary diversity on health status among Chinese older adults.

Methods
There were 5740 sample participants aged 65 and above selected from the Chinese Longitudinal Healthy Longevity Survey, among which 3334 samples in 2018 wave and 2406 samples in 2011 wave. Dietary diversity was assessed by Dietary Diversity Score ranged from 0 to 9, the higher the score, the better dietary diversity. Health status was assessed into healthy, impaired and dysfunctional state by three indicators: Activities of Daily Living, Instrument Activities of Daily Living and Mini-Mental State Examination. Multinomial logistic regression was employed to assess the effects of dietary diversity on the health status among the elderly. Heterogeneity analysis between different groups by age was further discussed.

Results
Older adults with better dietary diversity are in better health status, the mean dietary diversity score for healthy group was higher than that of impaired and dysfunctional groups (In 2018 wave, the scores were 6.54, 6.26 and 5.92, respectively; and in 2011 wave, they were 6.38, 5.93 and 5.71, respectively). Heterogeneity analysis shows that the younger groups tend to have more diversified dietary and be in better health status. Dietary diversity was more significantly associated with health status of the younger elderly (OR, 1.22, 95% CI, 1.04–1.44, p < 0.05) than the older elderly (OR, 1.01, 95% CI, 0.37–2.78, p > 0.05) in 2018 wave; and in 2011 wave, dietary diversity was more significantly related to health status among the younger elderly (OR, 1.62, 95% CI, 1.26–2.08, p < 0.001) than the older elderly (OR, 0.08, 95%CI, 0.31–1.94, p > 0.05).

Conclusions
Better dietary diversity has positive effects on health status and is more significantly related to the younger elderly than the older elderly. So interventions including available dietary diversity assessment, variety of dietary assistance services in daily life, keeping nutrient digestion and absorption capacity for the venerable age might benefit to ensure the effects of dietary diversity on health status among older adults especially in maintaining intrinsic ability and physical function. In addition, healthy lifestyle should also be recommended.
The hidden burden of dysmenorrhea among adolescent girls in Palestine refugee camps: a focus on well-being and academic performance
Authors: Ghandour Rula , Hammoudeh Weeam , Stigum Hein , Giacaman Rita , Fjeld Heidi , Holmboe-Ottesen Gerd 
Published: March 2024

Abstract
Background
Dysmenorrhea (painful menstruation) is a condition that may have a profound effect on adolescent girls’ health status and well-being. It can impede their engagement in daily activities and hamper their regular school attendance. This study aims to explore the relationship between dysmenorrhea, well-being, and academic performance among adolescent girls living in Palestine refugee camps in the West Bank and Jordan.

Methods
We conducted a household survey between June and September 2019, with a total sample of 2737 adolescent girls 15 to 18 years old. Dysmenorrhea severity was assessed using the Working Ability, Location, Intensity, Duration of pain Dysmenorrhea scale (WaLIDD). The WHO-5 scale was used to evaluate the girls’ overall well-being. Menstrual academic disruption (MAD) was measured using a self-reported scale. Multiple linear regression models were employed to evaluate the association between dysmenorrhea, well-being, and academic performance. Directed Acyclic Graphs (DAGs) were employed to identify variables for control in regression models.

Results
The mean dysmenorrhea score was 6.6 ± 2.6, with 37.9% and 41.2% expressing moderate and severe symptoms, respectively. The mean WHO-5 score was 58.7 ± 25.1, and 34.9% reported a low well-being status. The mean MAD score was 3.1 ± 3.3. 26% reported missing school due to dysmenorrhea, 36% said dysmenorrhea impacted their ability to concentrate, and 39% were unable to study for tests, and complete homework. The first regression analysis showed a reduction of 1.45 units in WHO-5 score for each unit increase in dysmenorrhea. The second regression analysis showed a non-linear increase in MAD score for increasing dysmenorrhea. For each dysmenorrhea score less than 4 (mild) there was a modest increase in MAD scores (coefficient 0.08, p-value = 0.006), and for each dysmenorrhea score above 4 there was a stronger increase in MAD scores (coefficient 0.95, p < 0.001).

Conclusion
Dysmenorrhea poses significant challenges to the well-being and academic performance of adolescent girls living in Palestine refugee camps. Collaborative efforts and multifaceted approaches are crucial to address dysmenorrhea effectively. This involves research, targeted interventions, culturally sensitive strategies, and fostering a supportive environment that empowers girls to thrive academically and beyond.