bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight change and all-cause and cause-specific mortality: A 25-year follow-up study
Authors: Yang Huan , Wang Jianbing , Wang Xiaokun , Sun Wanyi , Tong Chenyunhao , Fan Jinhu , Qiao Youlin , Abnet Christian C. 
Published: January 2024

Abstract

Background:
Whether the dynamic weight change is an independent risk factor for mortality remains controversial. This study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial (NIT) cohort.

Methods:
Body weight of 21,028 healthy residents of Linxian, Henan province, aged 40–69 years was measured two times from 1986 to 1991. Outcome events were prospectively collected up to 2016. Weight maintenance group (weight change <2 kg) or stable normal weight group was treated as the reference. Cox proportional hazard model was performed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the risk of mortality.

Results:
A total of 21,028 subjects were included in the final analysis. Compared with the weight maintenance group, subjects with weight loss ≥2 kg had an increased risk of death from all-cause (HRAll-cause = 1.14, 95% CI: 1.09–1.19, P <0.001), cancer (HRCancer = 1.12, 95% CI: 1.03–1.21, P = 0.009), and heart disease (HRHeart diseases = 1.21, 95% CI: 1.11–1.31, P <0.001), whereas subjects with weight gain ≥5 kg had 11% (HRCancer = 0.89, 95% CI: 0.79–0.99, P = 0.033) lower risk of cancer mortality and 23% higher risk of stroke mortality (HRStroke = 1.23,95% CI: 1.12–1.34, P <0.001). For the change of weight status, both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death (HROverweight to normal = 1.18, 95% CI: 1.09–1.27; HRBecoming underweight = 1.35, 95% CI: 1.25–1.46) and cancer death (HROverweight to normal = 1.20, 95% CI: 1.04–1.39; HRBecoming underweight = 1.44, 95% CI: 1.24–1.67), while stable overweight could increase the risk of total death (HRStable overweight = 1.11, 95% CI: 1.05–1.17) and death from stroke (HRStable overweight = 1.44, 95% CI: 1.33–1.56). Interaction effects were observed between age and weight change on cancer mortality, as well as between baseline BMI and weight change on all-cause, heart disease, and stroke mortality (all P
interaction <0.01).

Conclusions:
Weight loss was associated with an increased risk of all-cause, cancer, and heart disease mortality, whereas excessive weight gain and stable overweight were associated with a higher risk of stroke mortality. Efforts of weight management should be taken to improve health status.

Trial registration:

https://classic.clinicaltrials.gov/, NCT00342654.
Normal Ileal Mucus is Inadequate for Epithelial Protection in Ileal Pouch Mucosa
Authors: Knowles Jonathan , Church James 
Published: January 2024

BACKGROUND:
Clinical, nonspecific pouchitis is common after restorative proctocolectomy for ulcerative colitis, but its cause is unknown. A possible lack of protection for the ileal mucosa in its role as a reservoir for colonic-type bacteria may be the missing piece in defining the causes of pouchitis.

OBJECTIVE:
Review the causes of pouchitis and introduce the hypothesis that inadequate mucus protection in the pouch combined with a predisposition to abnormal inflammation is the most common cause of nonspecific pouchitis.

DATA SOURCES:
Review of PubMed and Medline for articles discussing pouchitis and intestinal mucus.

STUDY SELECTION:
Studies published from 1960 to 2023. The main search terms were “pouchitis,”,and “intestinal mucus,” while Boolean operators were used with multiple other terms to refine the search. Duplicates and case reports were excluded.

MAIN OUTCOME MEASURES:
Current theories about the etiology of pouchitis, descriptions of the role of mucus in the physiology of intestinal protection, and evidence of the effects of lack of mucus on mucosal inflammation.

RESULTS:
The cross-reference of “intestinal mucus” with “pouchitis” produced 9 references, none of which discussed the role of mucus in the development of pouchitis. Crossing “intestinal mucus” with “pouch” resulted in 32 papers, combining “pouchitis“ with “barrier function” yielded 37 papers and “pouchitis” with “permeability” only 8. No paper discussed the mucus coat as a barrier to bacterial invasion of the epithelium or mentioned inadequate mucus as a factor in pouchitis. However, an ileal pouch produces a colonic environment in the small bowel, and the ileum lacks the mucus protection needed for this sort of environment. This predisposes pouch mucosa to bacterial invasion and chronic microscopic inflammation that may promote clinical pouchitis in patients prone to an autoimmune response.

LIMITATIONS:
No prior studies address inadequate mucus protection and the origin of proctitis. There is no objective way of measuring the autoimmune tendency in patients with ulcerative colitis.

CONCLUSIONS:
Studies of intestinal mucus in the ileal pouch and its association with pouchitis are warranted.
Remnant cholesterol as a new lipid-lowering target to reduce cardiovascular events
Authors: Raggi Paolo , Becciu Maria Laura , Navarese Eliano P. 
Published: January 2024

Purpose of review
Remnant cholesterol has become increasingly recognized as a direct contributor to the development of atherosclerosis and as an additional marker of cardiovascular risk. This review aims to summarize the pathophysiological mechanisms, and the current evidence base from epidemiological investigations and genetic studies that support a causal link between remnant cholesterol and atherosclerotic cardiovascular disease. Current and novel therapeutic approaches to target remnant cholesterol are discussed.

Recent findings
A recent Mendelian randomization study of over 12 000 000 single-nucleotide polymorphisms associated with high levels of remnant cholesterol, demonstrated a genetic association between remnant cholesterol and adverse cardiovascular events among 958 434 participants.

Summary
In this light, the emerging role of remnant cholesterol as an independent lipid risk marker warrants a reevaluation of lipid management guidelines and underscores the potential for novel therapeutic targets in cardiovascular disease prevention.
Marker-controlled watershed algorithm and fuzzy C-means clustering machine learning: automated segmentation of glioblastoma from MRI images in a case series
Authors: Ghaderi Sadegh , Mohammadi Sana , Ghaderi Kayvan , Kiasat Fereshteh , Mohammadi Mahdi 
Published: January 2024

Introduction and importance:
Automated segmentation of glioblastoma multiforme (GBM) from MRI images is crucial for accurate diagnosis and treatment planning. This paper presents a new and innovative approach for automating the segmentation of GBM from MRI images using the marker-controlled watershed segmentation (MCWS) algorithm.

Case presentation and methods:
The technique involves several image processing techniques, including adaptive thresholding, morphological filtering, gradient magnitude calculation, and regional maxima identification. The MCWS algorithm efficiently segments images based on local intensity structures using the watershed transform, and fuzzy c-means (FCM) clustering improves segmentation accuracy. The presented approach achieved improved segmentation accuracy in detecting and segmenting GBM tumours from axial T2-weighted (T2-w) MRI images, as demonstrated by the mean characteristics performance metrics for GBM segmentation (sensitivity: 0.9905, specificity: 0.9483, accuracy: 0.9508, precision: 0.5481, F_measure: 0.7052, and jaccard: 0.9340).

Clinical discussion:
The results of this study underline the importance of reliable and accurate image segmentation for effective diagnosis and treatment planning of GBM tumours.

Conclusion:
The MCWS technique provides an effective and efficient approach for the segmentation of challenging medical images.
Emerging treatment options for skin and soft tissue infections tailoring drug selection to individual patients
Authors: Castaldo Nadia , Vena Antonio , Limongelli Alessandro , Giacobbe Daniele Roberto , Bassetti Matteo 
Published: January 2024

Purpose of review
To provide a brief overview of drugs in Phase II and III of development for the treatment of acute bacterial skin and skin structure infections (ABSSSI), offering insights into potential customized treatment options.

Recent findings
Several drugs are currently in advanced stages of evaluation for the treatment of ABSSSI, and numerous molecules are entering in the early development phases. Notably, many of these drugs exhibit unique mechanisms of action and interesting antimicrobial spectrum.

Summary
Tailoring antibiotic therapy based on patient characteristics, likely pathogens, type, site and severity of ABSSSI is crucial. Given the inherent limitations of available treatments, the development of novel agents is a pivotal avenue. Such advancements hold promise for enhancing treatment efficacy and simplifying drug selection for ABSSSI in everyday clinical practice.
Optical Coherence Tomography Parameters and Optimal Cut-off Values for Predicting Visual Prognosis in Ethambutol-Induced Optic Neuropathy
Authors: Kang Min Chae , Eun Hyung Woo , Park Kyung-Ah , Oh Sei Yeul 
Published: January 2024

Background:
The objective of this study was to evaluate the prognostic value of optical coherence tomography (OCT) parameters in patients with ethambutol-induced optic neuropathy (EON) and establish their optimal cut-off values for predicting visual acuity outcomes.

Methods:
A retrospective cross-sectional study was conducted on 64 eyes of 32 patients with EON who underwent OCT. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were measured using Cirrus high-definition OCT (HD-OCT) within 3 months after EON diagnosis. Visual acuity of patients was recorded and analyzed at the first visit, the 1-year visit, and the latest visit. Prognostic capacities of OCT parameters for visual prognosis were evaluated and their optimal cut-off values for predicting final visual acuity were established.

Results:
Increased pRNFL thickness was significantly associated with better visual acuity at 1 year postdiagnosis and the latest visit. A significant association was established between increased pRNFL thickness and a higher rate of recovery to visual acuity >20/25 at 1 year postdiagnosis. Receiver-operating characteristic curves identified ideal cut-off values for OCT parameters as follows: pRNFL thickness of 83 μm (sensitivity 100%, specificity 48.3%) and mGCIPL thickness of 74 μm (sensitivity 100%, specificity 83.3%) for visual acuity >20/25 at 1 year, mGCIPL thickness of 61 μm (sensitivity 85.7%, specificity 71.4%) for visual acuity >20/40 at 1 year, with corresponding AUCs exceeding 0.7.

Conclusions:
Both pRNFL and mGCIPL thickness possess potential values for predicting visual outcomes in patients with EON. Future research should continue to explore the utility of OCT parameters in EON prognosis.
T-Cell-Mediated Killing in Glioblastoma Organoids induced by Adenoviral Delivery of the CIITA Transgene
Authors: Salvato Ilaria , Klein Eliane , Poli Aurélie , Rezaeipour Mahsa , Ermini Luca , Nosirov Bakhtiyor , Lipsa Anuja , Oudin Anais , Baus Virginie , Dore Gian Mario , Cosma Antonio , Golebiewska Anna , Marchini Antonio , Niclou Simone P. 
Published: January 2024

ABSTRACTThe immunosuppressive nature of the tumor microenvironment poses a significant challenge to effective immunotherapies against glioblastoma (GB). Boosting the immune response is critical for a successful therapy. Here, we adopted a cancer gene therapy approach to induce T-cell mediated killing of the tumor through increased activation of the immune system. Patient-based 3D GB models were infected with a replication-deficient adenovirus (AdV) armed with the Class II Major Histocompatibility Complex (MHC-II) TransactivatorCIITAgene (Ad-CIITA). Successful induction of surface MHC-II was achieved in infected GB cell lines and primary human GB organoids. Infection with an AdV carrying a mutant form ofCIITAwith a single amino acid substitution resulted in cytoplasmic accumulation of CIITA without subsequent MHC-II expression. Co-culture of infected tumor cells with either PBMCs or isolated T-cells led to dramatic breakdown of GB organoids. Intriguingly, both wild-type and mutant Ad-CIITA but not unarmed AdV, triggered immune-mediated tumor cell death in the co-culture system, suggesting an at least partially MHC-II-independent process. We further show that the observed cancer cell killing requires the presence of either CD8+or CD4+T-cells and the direct contact between GB and immune cells. We did not however detect evidence of activation of canonical T-cell mediated cell death pathways. While the precise mechanism remains to be determined, these findings highlight the potential of AdV-mediatedCIITAdelivery to enhance T-cell-mediated immunity against GB.
Self-amplifying ROS-sensitive SN38 Dimeric Prodrug nanoparticles for Combined Chemotherapy and Ferroptosis in Cancer Treatment
Authors: Qin Yu , Wang Fenghui , Gao Zeping , Tian Chutong , Kamei Ken-ichiro 
Published: January 2024

AbstractChemotherapy drugs are often limited by their own clinical shortcomings and serious adverse consequences. To solve these problems, we developed a self-amplifying reactive oxygen species (ROS)-sensitive dimeric prodrug nanoparticles, namely SN38-CA@FC NPs for tumor treatment. A ROS-sensitive 7-ethyl-10-hydroxycamptothecin (SN38) prodrug (SN38-CA) was synthesized by a thioacetal linker between SN38 and the ROS generator cinnamaldehyde (CA). The subsequent release of SN38 inflicts DNA damage, exerting chemotherapeutic effects, while the liberated CA intensifies ferroptosis through Fenton reaction-mediated disruption of the redox balance. This dual-action strategy not only leverages chemotherapy but also induces ferroptosis, establishing a synergistic therapeutic paradigm. The system is uniquely characterized by a positive feedback loop where ROS instigates the release of SN38/CA, which in turn promotes further ROS production. In experimental evaluations, this combination therapy exhibited potent antitumor activity against both A549 and LLC cancer cell lines, as well as in xenograft LLC-bearing C57BL/6 mouse models. Collectively, our findings introduce a transformative Nano-Drug Delivery System (NDDS) that holds significant promise for advancing cancer chemotherapy and ferroptosis-based therapies.
The effects of intermittent or continuous exercise on renal haemodynamics during moderate-intensity exercise
Authors: Kawakami Shotaro , Yasuno Tetsuhiko , Kawakami Saki , Ito Ai , Fujimi Kanta , Matsuda Takuro , Nakashima Shihoko , Masutani Kosuke , Uehara Yoshinari , Higaki Yasuki , Michishita Ryoma 
Published: January 2024

AbstractPurposeModerate-intensity exercise has beneficial effects for individuals with CKD. However, it is unclear whether intermittent exercise (IE) has a different effect on renal haemodynamics compared to continuous exercise (CE). This study aimed to compare the effects of intermittent or continuous exercise on renal haemodynamics and renal injury during moderate-intensity exercise.MethodsTen males underwent IE or CE to consider the effect of exercise on renal haemodynamics during moderate-intensity exercise. Renal haemodynamic assessment and blood-sampling were conducted before exercise (pre) and immediately (post 0), 30-min (post 30), and 60-min (post 60) after exercise. Urine-sampling was conducted in pre, post 0 and post 60.ResultsThere was no condition-by-time interaction (p = 0.073), condition (p = 0.696), or time (p = 0.433) effects regarding renal blood flow. There was a condition-by-time interaction effect regarding noradrenaline concentrations (p = 0.037). Moreover, both conditions significantly increased noradrenaline concentration at post 0 (IE: p = 0.003, CE: p < 0.001) and remained significantly higher in post 30 (p < 0.001) and post 60 (p < 0.001). Significant difference was found in noradrenaline concentrations at post 0 when comparing IE and CE (399 ± 119 vs. 552 ± 224 pg/ml, p = 0.037). Urinary neutrophil gelatinase-associated lipocalin concentrations increased at post 60 (p = 0.009), but none of them exceeded the cutoff values for the definition of renal damage. Other renal injury biomarkers showed a similar pattern.ConclusionThese findings suggest that IE has a similar effect on renal haemodynamics and function, and AKI biomarkers compared to CE.
MAARU: Multichannel Acoustic Autonomous Recording Unit for spatial ecosystem monitoring
Authors: Heath Becky E , Le Penru Neel P , Skinner James , Orme C. David L. , Sethi Sarab S , Ewers Robert M , Picinali Lorenzo 
Published: January 2024

1.ABSTRACT1 – Acoustic localisation, which relies on simultaneous multi-microphone recording, adds spatial information to recorded audio and has been used in ecosystem monitoring to count individuals to improve abundance estimates, locate illegal activities such as logging/poaching, and monitor behaviour such as habitat use or species interactions. Studies have shown many advantages of acoustic localisation, but uptake remains limited as the equipment is often expensive, inaccessible, or only suitable for short-term deployments.2 –Here, we present a low-cost, open-source, 6-channel recorder built entirely from commercially available components which can be integrated into a solar-powered, networked system. The MAARU (Multichannel Acoustic Autonomous Recording Unit) works in long-term autonomous, passive, and ad-hoc deployments. We introduce MAARU’s hardware and software and present the results of lab and field tests investigating the device’s durability, localisation accuracy, and other applications.3 –MAARU provides multichannel data with similar costs and power demands to equivalent omnidirectional recorders. MAARU devices have been deployed in the UK and Brazil, where we have shown MAARUs can accurately localise pure tones up to 6kHz and 65dB bird calls as far as 8m away (±10° range, 100% and >60% of signals respectively), louder calls may have even further detection radii. We also show how beamforming can be used on MAARU devices to improve species ID confidence scores by 20%+ and recall by 10%+ when using the BirdNET automated bird identification algorithms.4 –MAARU is an accessible, low-cost option for those looking to explore spatial soundscape ecology accurately and easily. Ultimately, the added directional element of the multichannel recording provided by MAARU allows for a new type of exploration into sonic environments.Abstract Figure
Opposing effects of acellular and whole cell pertussis vaccines onBordetella pertussisbiofilm formation, Siglec-F+ neutrophil recruitment and bacterial clearance in mouse nasal tissues
Authors: Hall Jesse M. , Gutiérrez-Ferman Jessica L. , Shamseldin Mohamed M. , Guo Myra , Gupta Yash A. , Deora Rajendar , Dubey Purnima 
Published: January 2024

AbstractDespite global vaccination, pertussis caused byBordetella pertussis(Bp) is resurging. Pertussis resurgence is correlated with the switch from whole cell vaccines (wPV) that elicit TH1/TH17 polarized immune responses to acellular pertussis vaccines (aPV) that elicit primarily TH2 polarized immune responses. One explanation for the increased incidence in aPV-immunized individuals is the lack of bacterial clearance from the nose. To understand the host and bacterial mechanisms that contribute toBppersistence, we evaluated bacterial localization and the immune response in the nasal associated tissues (NT) of naïve and immunized mice followingBpchallenge.Bpresided in the NT of unimmunized and aPV-immunized mice as biofilms. In contrast,Bpbiofilms were not observed in wPV-immunized mice. Following infection, Siglec-F+ neutrophils, critical for eliminatingBpfrom the nose, were recruited to the nose at higher levels in wPV immunized mice compared to aPV immunized mice. Consistent with this observation, the neutrophil chemokine CXCL1 was only detected in the NT of wPV immunized mice. Importantly, the bacteria and immune cells were primarily localized within the NT and were not recovered by nasal lavage (NL). Together, our data suggest that the TH2 polarized immune response generated by aPV vaccination facilitates persistence in the NT by impeding the infiltration of immune effectors and the eradication of biofilms In contrast, the TH1/TH17 immune phenotype generated by wPV, recruits Siglec-F+ neutrophils that rapidly eliminate the bacterial burden and prevent biofilm establishment. Thus, our work shows that aPV and wPV have opposing effects onBpbiofilm formation in the respiratory tract and provides a mechanistic explanation for the inability of aPV vaccination to control bacterial numbers in the nose and prevent transmission.Author SummaryAcellular pertussis vaccine (aPV) immunized individuals maintain a nasal reservoir ofBordetella pertussis(Bp) and thus have the potential to transmit the infection to vulnerable individuals. Here we provide a mechanistic explanation for the inability of aPV to eliminateBpfrom the nasal cavity. We show that following bacterial challenge of aPV immunized mice, Siglec-F+ neutrophils and other immune effectors are not recruited to the nose. Consequently,Bpremain in the nose and form biofilms. In contrast, whole cell pertussis (wPV) immunized mice produce immune effectors following bacterial challenge that recruit Siglec-F+ neutrophils to the nose.Bpburden is cleared from the nasal tissues, thereby preventing bacterial persistence and the formation of biofilms.
Implications of noncoding regulatory functions in the development of insulinomas
Authors: Ramos-Rodríguez Mireia , Subirana-Granés Marc , Norris Richard , Sordi Valeria , Fernández Ruiz Ángel , Fuentes-Páez Georgina , Pérez-González Beatriz , Berenguer Balaguer Clara , Raurell-Vila Helena , Chowdhury Murad , Corripio Raquel , Partelli Stefano , López-Bigas Núria , Pellegrini Silvia , Montanya Eduard , Nacher Montserrat , Falconi Massimo , Layer Ryan , Rovira Meritxell , Gonzalez-Perez Abel , Piemonti Lorenzo , Pasquali Lorenzo 
Published: January 2024

SummaryInsulinomas are rare neuroendocrine tumours arising from the pancreatic β-cells. While retaining the ability to produce insulin, insulinomas feature aberrant proliferation and altered hormone secretion resulting in failure to maintain glucose homeostasis.With the aim of uncovering the role of noncoding regulatory regions and their aberrations to the development of these tumors, we coupled epigenetic and gene expression profiling with whole-genome sequencing. As a result, we mapped H3K27ac sites in the tumoral tissue and unraveled overlapping somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development and epigenetic modifying genes, including key components of the polycomb complex. Chromatin remodeling is apparent as insulinoma-selective regions are mostly clustered in regulatory domains, shared across patients and containing a specific set of regulatory sequences dominated by the binding motif of the transcription factor SOX17. Moreover, a large fraction of these regions are H3K27me3-repressed in unaffected β-cells, suggesting that tumoral transition is coupled with derepression of β-cell polycomb-targeted domains.Our work provides a compendium of aberrantcis-regulatory elements and transcription factors that alter β-cell function and fate in their progression to pancreatic neuroendocrine tumors and a framework to identify coding and noncoding driver mutations.