bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting Professionalism, Provoking Precarity: Security Assistance and the Risk of Military Coups
Authors: Darnton Christopher 
Published: January 2025

Abstract
When does foreign military assistance actually protect recipient governments, and when does it catalyze coups against them? In Adam Casey's Up in Arms: How Military Aid Stabilizes—and Destabilizes—Foreign Autocrats, great powers come preloaded with military models from their own history. These have different political risk profiles when exported, and the U.S. template of apolitical professionalism is particularly dangerous. This article reviews Up in Arms’ arguments about the sources and consequences of civil-military relationships, comparative Cold War case studies on the track record of security assistance and political regime durability, and contemporary policy lessons for military aid and alliances in an era of great power competition. It contextualizes these findings with the broader security assistance literature's mixed empirical results regarding democracy, human rights, and defense capability in recipient countries, and with scholars’ increasing emphasis, across research methods, on military training and education. In critiquing scope and methods both for the book and the field, the article calls for more case study work on democratic and counterinsurgent successes; closer analysis of military documents; and more systematic institutional disaggregation and ideational process tracing to assess the channels and conditions for effective security assistance.
Nutraceutical and low energy shockwave treatments improved sexual function recovery in a rat pelvic neurovascular injury model
Authors: Crisostomo-Wynne Theodore C , Hertz Alexandria M , Ferrini Monica G , Brand Timothy C , Salgar Shashikumar K 
Published: January 2025

Abstract

Background
Pelvic trauma can have long-lasting debilitating effects, including severe erectile dysfunction (ED) in men. While there are effective treatments for ED, these treat the symptoms not the cause. Those who suffer from an acute traumatic injury to the neurovascular supply of penis, may benefit from regenerative therapy. COMP4 is an all-natural herbal compound (Muira puama, Paullinia cupana, Ginger, and L-Citrulline) has potential to enhance penile vascular/smooth muscle/neuronal regeneration via Nitric Oxide synthesis. Low energy shockwave (LESW) therapy promotes nerve regeneration/angiogenesis by activating stem/progenitor cells.

Aim
To investigate the effects of the COMP4 and LESW for the treatment of ED in a rat pelvic trauma model.

Methods
The experimental design included five groups (Lewis rats aged 10-12 weeks; n = 8/group): (1) Sham, (2) Injury control, (3) Peanut Butter (PNB; Vehicle) Control, (4) COMP4, and (5) COMP4 + LESW. Pelvic neurovascular injury (PNVI) was induced by performing bilateral cavernous nerve crush injury and internal pudendal bundle ligation under general anesthesia. One week after PNVI rats received COMP4 (45 mg/kg b.wt./day) orally via PNB and/or LESW (1000 pulses at 0.06 mJ/mm2, 3 Hz, three times per week to the pelvis around penis) for 6 weeks. After 1 week of washout period, erectile function (EF) was assessed via intracavernous pressure (ICP; mmHg) measurements; rats euthanized, penile tissues collected for analyses.

Outcomes
COMP4 and LESW treatments improved EF recovery.

Results
There was a significant (P &lt; .01) improvement in EF (ICP) with COMP4 (153.6 ± 26.6) and COMP4 + LESW (174.1 ± 38.2) treatments compared to vehicle (PNB) control (109.4 ± 32.6). COMP4 + LESW treatment enhanced EF compared to COMP4 alone. The base level ICP before treatments (Group 2) was 117.3 ± 6 and was lower (P &lt; .01) than sham (165 ± 43.8) and COMP4 & COMP4 + LESW treated rats. Masson’s trichrome staining of corpus cavernosum penis demonstrated reduced (P &lt; .001) smooth muscle-to-collagen (SM:C) ratio in injury and PNB controls compared to sham. COMP4 treatment following PNVI showed an increase (P &lt; .05) in SM:C ratio. Adding LESW and COMP4 enhanced (P &lt; .01) the SM:C ratio, suggesting a reduction in fibrosis. Western blot analysis revealed a significant increase in Endothelial Nitric Oxide Synthase and α-Smooth Muscle Actin (α-SMA) in the corpus cavernosum with COMP4 and COMP4 + LESW treatments compared to PNB control.

Clinical Implications
COMP4 and/or LESW can serve as an adjunct therapy to mitigate ED.

Strengths and Limitations
Identified novel treatment option to improve EF recovery. Unable to address in-depth cellular/molecular mechanisms.

Conclusions
COMP4 and LESW treatments appear to be promising to improve clinical EF recovery in pelvic trauma.
Customizing Tacrolimus Dosing in Kidney Transplantation: Focus on Pharmacogenetics
Authors: Lloberas Nuria , Vidal-Alabró Anna , Colom Helena 
Published: January 2025

Abstract:
Different polymorphisms in genes encoding metabolizing enzymes and drug transporters have been associated with tacrolimus pharmacokinetics. In particular, studies on CYP3A4 and CYP3A5, and their combined cluster have demonstrated their significance in adjusting tacrolimus dosing to minimize under- and overexposure thereby increasing the proportion of patients who achieve tacrolimus therapeutic target. Many factors influence the pharmacokinetics of tacrolimus, contributing to inter-patient variability affecting individual dosing requirements. On the other hand, the growing use of population pharmacokinetic models in solid organ transplantation, including different tacrolimus formulations, has facilitated the integration of pharmacogenetic data and other variables into algorithms to easier implement the personalized dose adjustment in transplant centers. The future of personalized medicine in transplantation lies in implementing these models in clinical practice, with pharmacogenetics as a key factor to account for the high inter-patient variability in tacrolimus exposure. To date, three clinical trials have validated the clinical application of these approaches. The aim of this review is to provide an overview of the current studies regarding the different population pharmacokinetic including pharmacogenetics and those translated to the clinical practice for individualizing tacrolimus dose adjustment in kidney transplantation.
Outcomes of Tongue Reduction Surgery in Beckwith-Wiedemann Syndrome: A Systematic Review
Authors: Abraha Beraki , MacIntyre Olivia , Brennan Hannah , Hong Paul , Bezuhly Michael 
Published: January 2025

Introduction:
Macroglossia is a frequent clinical feature of Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth disorder. Macroglossia can lead to abnormal breathing, feeding, speech, and dentoskeletal development. Partial glossectomy is a common intervention aimed at reducing these abnormalities. The optimal timing of partial glossectomy remains controversial due to the potential need for secondary surgery and the ongoing growth of the tongue in early childhood.

Materials and Methods:
After PRISMA-ScR and PRISMA-S reporting standards, this systematic review included English language studies of patients with BWS who underwent partial glossectomy. Data were extracted, including patient age, clinical outcomes, and follow-up. Study evidence levels were categorized based on a recognized hierarchy, and bias was assessed using the MINORS criteria.

Results:
Early tongue reduction surgery (<24 mo) was associated with a lower incidence of class 3 occlusion and anterior open bite compared with later surgery. Improvements in speech intelligibility, tongue mobility, and breathing outcomes, including a reduction in obstructive sleep apnea, were observed, especially in early surgical groups. Feeding and drooling outcomes improved across both early and late surgical interventions, although no direct comparisons were made between the 2. Overall, tongue reduction surgery demonstrated benefits in functional outcomes, whereas dentoskeletal improvements remained variable.

Conclusion:
Although there is a lack of consensus to the optimal age for the procedure, overall tongue reduction surgery in BWS seems to have functional benefits, including in speech, feeding, and breathing. Dentoskeletal outcomes are more variable. Variability in macroglossia severity, surgical technique, and surgeon experience may account for differences in reported outcomes across studies.
Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids Presenting With Predominantly Neuro-Ophthalmic Features
Authors: McDonald Heather M. , Handzic Armin , Mandell Daniel M. , Donaldson Laura , Trobe Jonathan D. , Margolin Edward 
Published: January 2025

Background:
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare and poorly understood inflammatory disorder of the central nervous system centered on the pons. It has a characteristic imaging appearance with enhancing and T2-hyperintense punctate and curvilinear lesions in the pons. The lesions lack restricted diffusion and have relatively little perilesional edema. Although patients typically present with gait ataxia and other sequelae of brainstem inflammation including diplopia, there is scant literature focusing on patients who present with primarily neuro-ophthalmic manifestations.

Methods:
Case series of 3 patients presenting with diplopia who had a final diagnosis of CLIPPERS.

Results:
Case descriptions of a 71-year-old man, 61-year-old woman, and 38-year-old man are reported. Diplopia was the chief presenting complaint, owing to internuclear ophthalmoplegia, sixth nerve palsy, or skew deviation. All patients had nystagmus and gait ataxia. Brain MRI displayed punctate or curvilinear enhancement of pontine/middle cerebellar peduncle lesions without restricted diffusion. All patients achieved rapid improvement after corticosteroid treatment.

Conclusions:
In 3 patients with CLIPPERS, the main presenting complaint was diplopia. The distinctive imaging signs led to a strong presumption of CLIPPERS, permitting a truncated evaluation and early corticosteroid treatment, which provided rapid reversal of clinical and imaging manifestations.
Rural Diets Under Pressure: Food Environments and their Influence on Food Choice in South Asia
Authors: Chauhan Alka , Scott Samuel , Joe William , Maharjan Nanda Kumar , Menon Purnima ,   TAFSSA collaborators, Chakrabarti Suman 
Published: January 2025

AbstractThe rapid South Asia rural transformation, driven by globalization and industrialization, has introduced a complex interaction between traditional and modern food systems. This study characterizes rural food environments in five districts across Bangladesh, India, and Nepal, focusing on how affordability, availability, accessibility, desirability, and convenience shape dietary choices and quality. Through extensive household and market surveys, we find rural diets characterized by low intake of healthy foods and moderate to high consumption of unhealthy options, influenced by a lack of affordability and the desirability and widespread availability of cheap ultra-processed products in rural markets. Snacking plays a significant role in shaping dietary patterns, promoting both dietary diversity and unhealthy food consumption. These findings provide essential insights for designing interventions tailored to rural food systems, supporting efforts to improve nutrition and health outcomes in rapidly changing markets.
Targeting and combating drug resistance in triple-negative breast cancer using nano polymer: Efficacy of A6 peptide-PLGA-PEG nanoparticle loaded with doxorubicin and anti-miR-21 inin vitroandvivo model
Authors: Ibrahim Zaidah , Chong Pei Pei , Al-Moustafa Hasan , Abdullah Maizaton Atmadini , Chik Zamri 
Published: January 2025

AbstractTriple-negative breast cancer (TNBC) poses a significant challenge in treatment due to the emergence of drug resistance to standard chemotherapeutics, along with associated risks to non-targeted tissues. This study is dedicated to developing a nanoparticle drug delivery system utilizing PLGA-PEG nanoparticles (NP) with the integration of A6 peptide (NPA6) as a specific targeting ligand for TNBC. Encapsulating Doxorubicin (DOX) and antisense-miR-21 (AM21), these nanoparticles are designed to counter drug resistance in vitro and in vivo. Characterized by an average size of 103.5 (±8.1) nm and remarkable DOX encapsulation efficiency, these nanoparticles have been successfully engineered. Results demonstrate that NPA6.DOX.AM21 effectively mitigates drug resistance, displaying a significantly decreased doxorubicin IC50as opposed to free DOX (2.5 µM vs 25.7µMrespectively, p<0.01). In mice models, the A6 peptide-incorporated formulation (NPA6.DOX, NPA6.DOX.AM21) exhibits substantial tumour size reduction and increased doxorubicin concentration within tumours, all while minimizing non-specific doxorubicin exposure compared to non-A6 formulations (NPDOX, FREE DOX) treatments. This innovative PLGA-PEG-A6 peptide complex loaded with DOX and AM21 showcases superior efficacy in surmounting cell resistance in breast cancer cell line, targeting tumour progression, and decreasing drug distribution in non-targeted organs in mice. These results hold promise for enhanced combat against drug resistance and precise chemotherapy, hence potentially improving patient outcomes and survival rates.Graphical abstactFigure Graphical abstract of the study. Fron left to right, development of nanoparticles formulation a followed by characterization and efficacy of the nanoparticle formulation inin vitroandin vivoto reduce drug resistance and target triple negative breast cancer (TNBC). PLGA: polylactic-co-glycolic acid, PEG: polyethylene glycol, A6: A6 peptide, DOX: Doxorubicin, AM21: antisense-microRNA -21HighlightsThe nanoparticle of A6 conjugated PLGA-PEG co-loaded Doxorubicin with anti-miRNA21 (NPA6.DOX.AM21) was successfully fabricated with the size of 99.8 - 103.5 nm diameter and PDI 0.2 with high drugs encapsulation efficiency.NPA6.DOX.AM21 increased cell death, reduced drug resistance in MDA MB-231 resistant cells, and reduced IC50of doxorubicin dose.NPA6.DOX.AM21 targeted and reduced TNBC tumour size, with high doxorubicin distribution in tumor and less accumulation in off-target organs, in comparison to the control in mice model.
Structural basis for postfusion-specific binding to Respiratory Syncytial Virus F protein by the canonical antigenic site I antibody 131-2a
Authors: Peng Weiwei , Šiborová Marta , Wu Xuesheng , Du Wenjuan , Schulte Douwe , Pronker Matti F. , de Haan Cornelis A. M. , Snijder Joost 
Published: January 2025

AbstractThe Respiratory Syncytial Virus (RSV) Fusion (F) protein is a major target of antiviral antibodies following natural infection or vaccination and responsible for mediating fusion between the viral envelope and the host membrane. The fusion process is driven by a large-scale conformational change in F, switching irreversibly from the metastable prefusion state to the stable postfusion conformation. Previous research has identified six distinct antigenic sites in RSV-F, termed sites Ø, I, II, III, IV, and V. Of these, only antigenic site I is fully specific to the postfusion conformation of F. A monoclonal antibody 131-2a that specifically targets postfusion F has been widely used as a research tool to probe for postfusion F and to define antigenic site I in serological studies, yet its sequence and precise epitope have remained unknown. Here we use mass spectrometry-basedde novosequencing of 131-2a to reverse engineer a recombinant product and study the epitope to define antigenic site I with molecular detail, revealing the structural basis for the antibody’s specificity towards postfusion RSV-F.
C-di-GMP is Required for Swarming inE. coli: a Role for DgcO and Colanic Acid
Authors: Hwang YuneSahng , Perez Marta , Holzel Rebecca , Harshey Rasika M. 
Published: January 2025

AbstractMany bacteria use flagella to swim individually through bulk liquid, or swarm collectively over a semi-solid surface. InE. coli, c-di-GMP inhibits swimming via the effector protein YcgR. We show in this study that contrary to its effect on swimming, a certain threshold level of c-di-GMP is required for swarming. Gene expression profiles first indicated that several c-di-GMP synthases –dgcJ, dgcM, dgcO- were upregulated during swarming. Of these, we found DgcO to play a critical role. DgcO is reported to affect PGA (poly-β-1,6-N-acetylglucosamine) synthesis inE. coli. We show that DgcO also promotes production of colanic acid - one of the three major exopolysaccharides inE. coli, and that colanic acid has hitherto-unknown surfactant properties that are expected to aid swarming.ImportanceIt is well-established that in bacteria, c-di-GMP inhibits flagella-driven motility at various points in the pathway. Concomitantly, elevated c-di-GMP levels induce the expression and synthesis of a variety of exopolysaccharides that enmesh the bacteria in a biofilm, thereby also interfering with flagella function. This study reports the surprising finding that inE. coli, the exopolysaccharide colanic acid is required to enable surface navigation and that the diguanylate cyclase DgcO is employed for this purpose. For surface navigation, there appears to be a sweet spot where c-di-GMP levels are just right to produce polysaccharides that can serve as surfactants and wetting agents rather than promote formation of biofilms.
Checkpoint receptors in circulating γδ T cells can discern the outcome of cancer immunotherapy
Authors: Catafal Tardos Elisa , Dachicourt Lola , Baglioni Maria Virginia , Fares da Silva Marcelo Gregorio Filho , Secci Davide , Donia Marco , Kverneland Anders , Svane Inge Marie , Bekiaris Vasileios 
Published: January 2025

AbstractGamma delta (γδ) T cells are innate-like lymphocytes that in humans can be broadly classified into two main subtypes based on their unique TCRδ chain, Vδ1 and Vδ2. Both subsets have potent anti-tumor properties and the presence of Vδ1 cells in the tumor is often associated with positive prognosis. Herein, we investigated the molecular interplay between immune checkpoint receptors (ICRs), IC blockade (ICB) therapy and γδ T cells. We show that ICRs display differential expression and regulation by the JAK-STAT pathway in circulating Vδ1 and Vδ2 cells and identify constitutive (e.g. TIGIT, PD-1) and inducible (e.g. TIM-3, LAG-3, CTLA-4) ICRs. In melanoma, Vδ1 cells, especially in patients who did not respond to ICB or required combination therapy, expressed high levels of ICR, TOX and inhibitory killer Ig-like receptors (KIR) transcripts, reminiscent of an exhaustion transcriptional signature. At the same time all γδ T cells had a prominent downregulation in AP-1 transcription factors. Patient derived cells were functionally competent, although induction of LAG-3 and CTLA-4 was impaired. In the context of anti-PD-1 monotherapy, Vδ1 cells specifically bound high levels of therapeutic antibody but only in patients who responded to treatment, revealing a potential new prognostic marker for evaluating the efficacy of ICB therapy. Finally, expression of KIR genes in Vδ1 cells was downregulated in response to successful ICB therapy. Collectively, our data indicate an intricate relationship between ICRs, putatively also KIRs, and γδ T cells and reveal novel approaches by which these cells can be harnessed in order to discern or improve cancer immunotherapy.
ANGPTL3 binds to PCSK9 to coordinately regulate intracellular lipid homeostasis
Authors: Bini Simone , Pecce Valeria , Grimaldos Alessandra Pinzon , Di Costanzo Alessia , Minicocci Ilenia , Covino Stella , Tramontano Daniele , Piconese Silvia , D’Erasmo Laura , Arca Marcello 
Published: January 2025

ABSTRACTANGPTL3 and PCSK9 are core proteins involved in lipid metabolism. Literature evidence highlights a potential mutual regulation between them: patients harboring loss-of-function variants in ANGPTL3 show reduced levels of circulating PCSK9. After predicting their interaction using an in-silico model, we verified the direct interaction between ANGPTL3 and PCSK9 through co-immunoprecipitation. The ANGPTL3-PCSK9 complex persisted underfastingconditions and dissociated underfeedingconditions. Treatment with human LDLs was sufficient to simulate the feeding response. Then, we observed that the overexpression of PCSK9 enhances the uptake of LDLs that are not further metabolized, while the overexpression of ANGPTL3 enhances LDL turnover. The overexpression of both proteins restored LDL uptake and degradation, which became comparable to those of control cells. In conclusion, our findings indicate the existence of an ANGPTL3-PCSK9 complex, which coordinately contributes to the regulation of intracellular lipid homeostasis, aiming to prevent cellular metabolic overload.GRAPHICAL ABSTRACTGraphical abstractMechanistic model of ANGPTL3-PCSK9 complex function in the regulation of lipoprotein metabolismIncreased uptake of extracellular nutrients determines the separation of the ANGPTL3-PCSK9 complex. The two free proteins have different functions (1). Increased levels of PCSK9 determine an increased intracellular entrapment of circulating LDLs (2) that are not catabolized unless there is a presence of high intracellular levels of ANGPTL3. Increased ANGPTL3 levels also favor ApoB lipidation and secretion (3), whereas an increase in intracellular PCSK9 increases intracellular ApoB degradation. The increase in intracellular PCSK9 also determines a block in lipogenesis and favors beta-oxidation, thus decreasing the intracellular lipid content (4).
Maternal immune activation imprints a regulatory T cell deficiency in offspring that drives an autism-like phenotype
Authors: Ellul Pierre , Fourcade Gwladys , Mhanna Vanessa , Coatnoan Nicolas , Bodula Susana , Seilhean Danielle , Mouton Laura , Marguerit Gwendolyn , Delorme Richard , Mi Tian , Youngblood Ben , Rosenzwajg Michelle , Tchitchek Nicolas , Klatzmann David 
Published: January 2025

AbstractMaternal immune activation (MIA) triggers an IL-17-driven autism spectrum disorder (ASD) in mouse and human offspring. While regulatory T cells (Tregs) regulate Th17 cells, their involvement in MIA and ASD pathogenesis is unknown. At the maternal level, we show that Treg stimulation suppresses interleukin-17 (IL-17) production and prevents ASD-like behaviors in offspring. At the offspring level, we show that MIA imprints a systemic and brain Treg deficiency, as evidenced by alterations in the methylome, transcriptome, and functional assays. This deficiency promotes brain inflammation, characterized by infiltration of IL-17–producing cells and neutrophils into the meninges and alterations in cortical brain structure. Stimulation of offspring Tregs with interleukin-2 reversed brain inflammation and cured established ASD-like behaviors. Thus, MIA-induced ASD is a neuroimmune disorder that can be reversed by immunomodulation.One sentence abstractMaternal immune activation during pregnancy imprints a Treg deficiency in offspring that perpetuates brain inflammation and an autism-like phenotype, which can be reversed by Treg stimulation.