bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nigrostriatal degeneration determines dynamics of glial inflammatory and phagocytic activity
Authors: Ayerra Leyre , Abellanas Miguel Angel , Basurco Leyre , Tamayo Ibon , Conde Enrique , Tavira Adriana , Trigo Amaya , Vidaurre Clara , Vilas Amaia , San Martin-Uriz Patxi , Luquin Esther , Clavero Pedro , Mengual Elisa , Hervás-Stubbs Sandra , Aymerich Maria S. 
Published: April 2024

AbstractGlial cells are key players in the initiation of innate immunity in neurodegeneration. Upon damage, they switch their basal activation state and acquire new functions in a context and time-dependent manner. Since modulation of neuroinflammation is becoming an interesting approach for the treatment of neurodegenerative diseases, it is crucial to understand the specific contribution of these cells to the inflammatory reaction and to select experimental models that recapitulate what occurs in the human disease. Previously, we have characterized a region-specific activation pattern of CD11b+ cells and astrocytes in the α-synuclein overexpression mouse model of Parkinson´s disease (PD). In this study we hypothesized that the time and the intensity of dopaminergic neuronal death would promote different glial activation states. Dopaminergic degeneration was induced with two administration regimens of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), subacute (sMPTP) and chronic (cMPTP). Our results show that in the sMPTP mouse model, the pro-inflammatory phenotype of striatal CD11b+ cells was counteracted by an anti-inflammatory astrocytic profile. In the midbrain the roles were inverted, CD11b+ cells exhibited an anti-inflammatory profile and astrocytes were pro-inflammatory. The overall response generated resulted in decreased CD4 T cell infiltration in both regions. Chronic MPTP exposure resulted in a mild and prolonged neuronal degeneration that generated a pro-inflammatory response and increased CD4 T cell infiltration in both regions. At the onset of the neurodegenerative process, microglia and astrocytes cooperated in the removal of dopaminergic terminals. With time, only microglia maintained the phagocytic activity. In the ventral midbrain, astrocytes were the main phagocytic mediators at early stages of degeneration while microglia were the major phagocytic cells in the chronic state. In this scenario, we questioned which activation pattern recapitulates better the features of glial activation in PD. Glial activation in the cMPTP mouse model reflects many pathways of their corresponding counterparts in the human brain with advanced PD. Altogether, our results point toward a context-dependent cooperativity of microglia/myeloid cells and astrocytes in response to neuronal damage and the relevance of selecting the right experimental models for the study of neuroinflammation.
Graphical abstract
Birthweight trends and their explanatory factors in Hungary between 1999 and 2018: an analysis of the Hungarian Tauffer registry
Authors: Zsirai László , Kun Attila , Visolyi Gergely Á. , Svébis Márk M. , Domján Beatrix A. , Tabák Ádám 
Published: April 2024

Abstract
Background
The increasing birthweight trend stopped and even reversed in several high income countries in the last 20 years, however the reason for these changes is not well characterized. We aimed to describe birthweight trends of term deliveries in Hungary between 1999 and 2018 and to investigate potential maternal and foetal variables that could drive these changes.

Methods
We analysed data from the Hungarian Tauffer registry, a compulsory anonymized data collection of each delivery. We included all singleton term deliveries in 1999–2018 (n = 1,591,932). We modelled birthweight trends separately in 1999–2008 and 2008–2018 in hierarchical multiple linear regression models adjusted for calendar year, newborn sex, maternal age, gestational age at delivery, and other important determinants.

Results
Median birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g in 2018. When we adjusted for gestational age at delivery the increase in the first period became more pronounced (5.4 g/year). During the second period, similar adjustment substantially decreased the rate of decline from 2.5 to 1.4 g/year. Further adjustment for maternal age halved the rate of increase to 2.4 g/year in the first period. During the second period, adjustment for maternal age had little effect on the estimate.

Conclusions
Our findings of an increasing birthweight trend (mostly related to the aging of the mothers) in 1999–2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, the long-term effect cannot be predicted, as the trend is mostly explained by the shorter pregnancies.
Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution
Authors: Pastor Rocío , Puyssegur Juliana , de la Guardia M. Paula , Varón Lindybeth Sarmiento , Beccaglia Gladys , Spada Nicolás , de Lima Andrea Paes , Collado M. Soledad , Blanco Andrés , Scetti Isabel Aspe , Arabolaza M. Elena , Paoli Bibiana , Chirdo Fernando , Arana Eloísa 
Published: April 2024

Abstract
Background
The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells.

Results
We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures.

Conclusions
This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites.
Urate-lowering therapy, serum urate, inflammatory biomarkers, and renal function in patients with gout following pegloticase discontinuation
Authors: Holladay Emily E. , Mudano Amy S. , Xie Fenglong , Zhang Jingyi , Mikuls Ted R. , LaMoreaux Brian , Padnick-Silver Lissa , Curtis Jeffrey R. 
Published: April 2024

Abstract
Background/Purpose
Little is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU), inflammatory biomarkers, and renal function following pegloticase discontinuation.

Methods
We conducted a retrospective analysis of gout patients who discontinued pegloticase using the Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 to 6/2022. We defined discontinuation as a gap ≥ 12 weeks after last infusion. We examined outcomes beginning two weeks after last dose and identified ULT therapy following pegloticase discontinuation. We evaluated changes in lab values (SU, eGFR, CRP and ESR), comparing on- treatment (≤ 15 days of the second pegloticase dose) to post-treatment.

Results
Of the 375 gout patients discontinuing pegloticase, median (IQR) laboratory changes following discontinuation were: SU: +2.4 mg/dL (0.0,6.3); eGFR: -1.9 mL/min (− 8.7,3.7); CRP: -0.8 mg/L (-12.8,0.0); and ESR: -4.0 mm/hr (-13.0,0.0). Therapy post-discontinuation included oral ULTs (86.0%), restarting pegloticase (4.5%), and no documentation of ULT (9.5%), excluding patients with multiple same-day prescriptions (n = 17). Oral ULTs following pegloticase were: 62.7% allopurinol, 34.1% febuxostat. The median (IQR) time to starting/restarting ULT was 92.0 days (55.0,173.0). Following ULT prescribing (≥ 30 days), only 51.0% of patients had SU < 6 mg/dL. Patients restarting pegloticase achieved a median SU of 0.9 mg/dL (IQR:0.2,9.7) and 58.3% had an SU < 6 mg/dL.

Conclusion
Pegloticase treats uncontrolled gout in patients with failed response to xanthine oxidase inhibitors, but among patients who discontinue, optimal treatment is unclear. Based on this analysis, only half of those starting another ULT achieved target SU. Close follow-up is needed to optimize outcomes after pegloticase discontinuation.
Subclinical epileptiform discharges in Alzheimer’s disease are associated with increased hippocampal blood flow
Authors: Musaeus Christian Sandøe , Kjaer Troels Wesenberg , Lindberg Ulrich , Vestergaard Mark B. , Bo Henrik , Larsson Wiberg , Press Daniel Zvi , Andersen Birgitte Bo , Høgh Peter , Kidmose Preben , Hemmsen Martin Christian , Rank Mike Lind , Hasselbalch Steen Gregers , Waldemar Gunhild , Frederiksen Kristian Steen 
Published: April 2024

Abstract
Background
In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer’s disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer’s disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus.

Methods
A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG.

Results
No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC.

Conclusions
Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD.

Trial registration
The study is registered at clinicaltrials.gov (NCT04436341).
False-negative factors of percutaneous transluminal clamp biopsy for suspected malignant biliary stricture: 194 cases analyzed from a single center
Authors: Zhang Chengzhi , Li Yipu , Song Mengyao , Sun Zhanguo , Han Xinwei , Ren Jianzhuang , Jiao Dechao 
Published: April 2024

Abstract
Objective
To study the predictive factors of false negatives in the diagnosis of biliary stricture (BS) by percutaneous transluminal clamp biopsy (PTCB).

Method
From January 2016 to January 2021, 194 patients with a high suspicion of malignant tumors due to BS underwent PTCB during biliary drainage at our department. The final diagnosis was confirmed by postoperative pathology, other tissue or cell evidence, or medical imaging follow-up. Univariate and multivariate regression analyses were performed on the pathological results, summarizing the independent risk factors for false-negative value (FNV) to help further clinical diagnosis and treatment.

Results
Of the 194 cases, 176 and 18 cases were finally diagnosed as malignant and benign BS, respectively, compared to 144 and 50 cases by PTCB, including 32 false-negative cases. The sensitivity, specificity, false-positive value, and FNV of PTCB were 81.8%, 100%, 0%, and 18.2%, respectively. Multivariate analysis showed that non-cholangiocarcinoma BS was an independent risk factor for FNV of PTCB (odds ratio 7.5 (95% CI 1.74–32.6), p < 0.01).

Conclusion
PTCB is an effective minimally invasive interventional technique for BS diagnosis. Non-cholangiocarcinoma BS is an independent risk factor for FNV.

Critical relevance statement
Identifying factors that are predictive of false-negative results by percutaneous transluminal clamp biopsy in the setting of biliary stricture may have a guiding effect on clinical practice.

Key points
• Factors predictive of false negatives in the diagnosis of biliary stricture etiology by PTCB may aid in the interpretation of results.
• Non-cholangiocarcinoma BS is an independent risk factor for FNV on PTCB.
• PTCB is an effective minimally invasive interventional technique for BS diagnosis.

Graphical Abstract
Graves’ disease thyroid dermopathy: a case report
Authors: Tashkandi Loay , Alsagheir Afaf , Alobaida Saud , Alhuthil Raghad 
Published: April 2024

Abstract
Background
Graves’ disease is the autoimmune activation of the thyroid gland causing diffuse enlargement and hyperfunction of the gland. Manifestations of Graves’ disease are multisystemic and include thyroid orbitopathy; pretibial myxedema, also referred to as thyroid dermopathy; and thyroid acropachy, described as a severe form of thyroid dermopathy. Our paper focuses on an atypical case of thyroid dermopathy.

Case presentation
An 11-year-old Saudi male presented with a prominent diffuse goiter and exophthalmos. Investigations were consistent with a diagnosis of Graves’ disease. The physical exam showed diffuse, non-pitting swelling of the ankle and penis, mimicking a lymphatic malformation. Further, multiple nodules were found on the hands and feet. Treatment of the nodules with cautery resulted in more severe nodules.

Conclusion
This report describes rare presentations of thyroid dermopathy mimicking lymphatic malformation. The Koebner phenomenon can explain this patient’s atypical presentations. Intralesional injections of triamcinolone and total thyroidectomy showed clear improvement.
Associations between Life’s Essential 8 and post-stroke depression and all-cause mortality among US adults
Authors: Ma Ruicong , Song Junting , Ding Yanchun 
Published: April 2024

Abstract
Background
Depression is the common mental disease after stroke. Our objective was to investigate the correlation of Life’s Essential 8 (LE8), the recently updated evaluation of cardiovascular health, with the occurrence of post-stroke depression (PSD) and all-cause mortality among United States (US) adults.

Methods
Participants with stroke were chosen from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The relationship between LE8 and the risk of PSD was assessed through weighted multiple logistic models. A restricted cubic spline was employed for the examination of correlations. To demonstrate the stability of the results, sensitivity analysis and subgroup analysis were carried out. Furthermore, Cox regression models were used for the correlation between LE8 and all-cause mortality.

Results
In this study, a total of 1071 participants were included for analysis. It was observed that LE8 score and PSD risk shared an inverse relationship in per 10 points increase [OR = 0.62 (0.52–0.74, P < 0.001)] in logistic regression models. The analysis of restricted cubic spline demonstrated approximately a noticeable inverse linear association between LE8 score and PSD risk. Sensitivity analysis verified the stability of the findings. Moreover, no statistically significant interactions were identified in subgroup analysis. A reverse association between LE8 score and all-cause mortality was also observed with a 10-point increase [HR = 0.85 (0.78–0.94, P < 0.001)] in cox regression models.

Conclusions
A negative correlation was discovered between LE8 score and PSD and all-cause mortality risk among US adults. We need to conduct large-scale prospective studies to further validate our results.
Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion
Authors: Lu Junli , Luo Yiming , Rao Dean , Wang Tiantian , Lei Zhen , Chen Xiaoping , Zhang Bixiang , Li Yiwei , Liu Bifeng , Xia Limin , Huang Wenjie 
Published: April 2024

AbstractParadoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs.
Statin use as a moderator on the association between metformin and breast cancer risk in women with type 2 diabetes mellitus
Authors: Zhang Fan , de Bock Geertruida H. , Landman Gijs W. , Zhang Qingying , Sidorenkov Grigory 
Published: April 2024

Abstract
Introduction
Metformin and statins are considered as potential agents for prevention of breast cancer, however, existing evidence does not uniformly substantiate this claim, and the data is scarce concerning their interaction in relation to breast cancer risk. This study aims to investigate whether the effect of metformin on breast cancer incidence varied by statin use among women with type 2 diabetes mellitus (T2DM).

Methods
This study included women with T2DM, without a history of cancers, and followed up for more than one year from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) for the period 1998–2014. The dataset was structured using a person-time approach, where the cumulative medication usage was annually updated for each person. The extended Cox proportional hazards models were employed, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI).

Results
During a median follow-up of 5 years, 515 of 29,498 women received a breast cancer diagnosis. Each additional year of metformin or statins use corresponded to a decrease in breast cancer incidence, while the magnitude attenuated over time. Noteworthily, statin use modified the effect of metformin on breast cancer incidence. For instance, after 5 years of follow-up, one-year increase of metformin use among women who used statins for 3 years was linked to a substantially reduced breast cancer risk (HR, 95% CI: 0.88, 0.84–0.93), however, there was no significant decrease in risk for those non-statins users (HR, 95% CI: 0.96, 0.89–1.04).

Conclusions
Extending metformin or statin usage by one year conferred breast cancer protection in women with T2DM. Enhanced protective effect of metformin was observed among those who also use statins. These results suggest the potential of combined metformin and statin therapy as promising breast cancer prevention strategies.
Towards an actionable One Health approach
Authors: Zhang Xiao-Xi , Lederman Zohar , Han Le-Fei , Schurer Janna M. , Xiao Li-Hua , Zhang Zhi-Bing , Chen Qiu-Lan , Pfeiffer Dirk , Ward Michael P. , Sripa Banchob , Gabriël Sarah , Dhama Kuldeep , Acharya Krishna Prasad , Robertson Lucy J. , Deem Sharon L. , Aenishaenslin Cécile , Dantas-Torres Filipe , Otranto Domenico , Grace Delia , Wang Yang , Li Peng , Fu Chao , Poeta Patrícia , Md. Tanvir Rahman  , Kassegne Kokouvi , Zhu Yong-Zhang , Yin Kun , Liu Jiming , Wang Zhao-Jun , Guo Xiao-Kui , Gong Wen-Feng , Schwartländer Bernhard , Ren Ming-Hui , Zhou Xiao-Nong 
Published: April 2024

Abstract
Background
Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact.

Main text
This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation.

Conclusions
By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Graphical Abstract