bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic and lifestyle factors accelerate disease onset and alter gut microbiome in inflammatory non-communicable diseases
Authors: Rohmann Nathalie , Geese Theresa , Nestel Samantha , Schlicht Kristina , Geisler Corinna , Türk Kathrin , Brix Fynn , Jensen-Kroll Julia , Demetrowitsch Tobias , Bang Corinna , Franke Andre , Lieb Wolfgang , Schulte Dominik M. , Schwarz Karin , Ruß Anne-Kathrin , Sharma Arunabh , Schreiber Stefan , Dempfle Astrid , Laudes Matthias 
Published: October 2024

Abstract

Background

Biomedical and lifestyle factors in Western populations have significantly shifted in recent decades, influencing public health and contributing to the increasing prevalence of non-communicable diseases (NCDs) that share inflammation as common pathology.

Methods
We investigated the relationship between these factors and 11 NCDs in the cross-sectional FoCus cohort (n = 1220), using logistic regression models. Associations with age-at-disease-onset were specifically analyzed for type 2 diabetes (T2D, low-grade chronic inflammation) and inflammatory bowel disease (IBD, high-grade chronic inflammation) in disease-specific cohorts (FoCus-T2D, n = 514; IBD-KC, n = 1110). Important factors for disease risk were identified using Cox-PH-regression models and time-to-event analysis. We further explored the interaction between identified risk factors and gut microbiome composition using linear models.

Results
Lifestyle factors were clearly linked to disease phenotypes, particularly in T2D and IBD. Still, some factors affected only the age-at-onset, but not disease prevalence. High-quality nutrition significantly delayed onset for both IBD and T2D (IBD: HR = 0.81 [0.66; 0.98]; T2D: HR = 0.45 [0.28; 0.72]). Smoking accelerated T2D onset (HR = 1.82 [1.25; 2.65]) but delayed onset in ulcerative colitis (UC: HR = 0.47 [0.28; 0.79]). Higher microbiota diversity delayed IBD onset (Shannon: HR = 0.58 [0.49; 0.71]) but had no effect on T2D. The abundance of specific microbial genera was strongly associated with various biomedical and lifestyle factors in T2D and IBD. In unaffected controls, these effects were smaller or reversed, potentially indicating a greater susceptibility of the gut microbiome to negative influences in T2D and IBD.

Conclusions
The dual insights into age-at-disease-onset and gut microbiota composition in disease emphasize the role of certain biomedical and lifestyle factors, e.g., nutrition quality, in disease prevention and management. Understanding these relationships provides a foundation for developing targeted strategies to mitigate the impact of metabolic and inflammatory diseases through lifestyle modifications and gut health management.
Assessing the role of non-state actors in health service delivery and health system resilience in Myanmar
Authors: Than K. , Bertone Maria Paola , La T. , Witter Sophie 
Published: October 2024

Abstract
Background
Due to the weaknesses of the public health system and its low reach, especially in border areas, provision of health services by non-state actors (NSAs) has historically played an important role in Myanmar. NSAs include local and international NGOs and civil society organisations (CSOs), but also Ethnic Health Organisations (EHOs) in the border areas, as well as the private (for profit) sector. This study aims to understand the changing role of NSAs in the shifting political environment of Myanmar between 2010 and 2022, and to explore their contribution to health system resilience.

Methods
Our study includes three main components: a documentary review (n = 22), key informant interviews (KIIs) at central level (n = 14) and two township-level case studies (13 KIIs, 4 FGDs). Mostly qualitative data were collected in 2022 and synthesized, using a health system resilience framework to structure the analysis.

Results
During the transition period (2010–2014) and the new political era (2015–2020), while the country gradually transitioned to a democratic system, the government increasingly recognized NSAs. Initially, engagement with NSAs remained focused on disease-specific activities and government oversight was limited, but later it expanded to health system strengthening, including the start of a “convergence” with ethnic health systems. Progress was relatively slow, but defined by a clear vision and plans. The military coup of February 2021 brought a halt to this progress. Collaboration between government and NSAs was interrupted, and NSAs restored previous practices and parallel systems. Initially, most health service provision stopped, but with time coping strategies emerged, which showed the capacity of NSAs to absorb the shocks (focusing on basic services; using informal communication channels; maintaining buffer stocks of supplies) and adapt (changing modes of delivery and supply chains, and adjusting HRH training).

Conclusions
The study highlights the role of NSAs during crises, and provides insights on how the resilience capacities built over time by NSAs to provide services in adverse circumstances have informed the response to the latest crisis. While strategies of absorption and adaptation are noted in the study, we did not identify any transformation strategy – which might indicate the difficulty of NSAs to introduce radical changes when subjected to multiple shocks and a hostile political environment.
Genetic analysis using next-generation sequencing and multiplex ligation probe amplification in Chinese aniridia patients
Authors: Wang Li , Xu Qingdan , Wang Wentao , Sun Xinghuai , Chen Yuhong 
Published: October 2024

Abstract
Background
Congenital aniridia is a rare pan-ocular disease characterized by complete irideremia, partial iridocoloboma. The progressive nature of aniridia is frequently accompanied by secondary ocular complications such as glaucoma and aniridia-associated keratopathy, which can lead to severely impaired vision or blindness. The genetic basis of aniridia has been the subject of numerous studies, leading to the development of innovative therapeutic options based on PAX6 nonsense mutations. Specific knowledge of the genetics of aniridia has become increasingly important. To report the clinical features, elucidate the genetic etiology, and reveal the mutational spectrum of congenital aniridia in the Chinese population, sixty patients with congenital aniridia from 51 families were recruited. Candidate genes associated with developmental eye diseases were identified and analyzed using panel-based next-generation sequencing (NGS), and mutations were confirmed through polymerase chain reaction and Sanger sequencing. Multiplex ligation probe amplification (MLPA) of PAX6 and FOXC1 was performed to detect copy number variations in the patients without intragenic mutations.

Results
Clinical examination revealed complete iris hypoplasia in 58 patients and partial iris hypoplasia in two patients. Additionally, two patients were diagnosed with Wilms’ tumor-aniridia-genital anomalies-retardation syndrome and nephroblastoma. By combining panel-based NGS and MLPA, 43 intragenic mutations or deletions of PAX6, FOXC1, and BCOR were identified in 59 patients, including 33 point mutations (76.7%) in 43 patients and 10 deletions (23.3%) in 16 patients. The total detection rate was 98.3%. Phenotypic variation was observed between and within families.

Conclusions
Variations in PAX6 and its adjacent regions were the predominant causes of aniridia in China. In addition to intragenic point mutations in PAX6, deletion of PAX6 or its adjacent genes is a common cause of congenital aniridia. Furthermore, FOXC1 is an important gene associated with congenital aniridia. The combination of panel-based NGS and MLPA significantly enhanced the detection rate of gene mutations in patients with congenital aniridia.
Safety and adherence of early oral immunotherapy for peanut allergy in a primary care setting: a retrospective cross-sectional study
Authors: Landry Victoria , Lewis Rachel , Lewis William , MacDonald Lyndsey , Carson Beth , Chandra Kavish , Fraser Jacqueline , Flewelling Andrew J. , Atkinson Paul , Vaillancourt Chris 
Published: October 2024

Abstract
Background
Peanut allergy is a common food allergy with potentially life-threatening implications. Early oral immunotherapy for peanut allergy (P-EOIT) has been shown to be effective and safe in research and specialty clinic settings. Provision of P-EOIT in primary care would make it available to more patients. We sought to assess the safety of P-EOIT in a primary care setting by documenting the rates of peanut-related allergic reactions leading to emergency department (ED) visits and use of epinephrine. We also examined adherence by assessing the percentage of patients reaching maintenance phase and continuing ingestion after one year of P-EOIT.

Methods
This retrospective study included all patients aged less than 36 months who started P-EOIT at a primary care allergy clinic in New Brunswick, Canada, from 2016 to 2020. The population included patients who (1) had a history of an allergic reaction to peanuts with a positive skin prick test or positive peanut specific IgE level (ps-IgE) or (2) no history of ingestion and a baseline ps-IgE ≥5 kU/L. Patients had biweekly clinic visits with graded increases in peanut protein up to a maintenance dose of 300 mg of peanut protein daily. A blinded retrospective review of paper charts and electronic medical records was conducted along with phone interviews regarding ED visits and epinephrine use.

Results
All 69 consented patients reached maintenance dose over a median of 29 weeks, and 66 patients (95.7%) were still regularly consuming peanut protein after 1 year of maintenance. One patient had a peanut ingestion-related ED visit requiring epinephrine during the escalation phase of peanut protein dosing (1.4%). During the first year of maintenance phase, no patients had peanut ingestion-related ED visits nor required epinephrine.

Conclusion
Early oral immunotherapy for peanut allergy in a primary care setting appears to be safe and our findings suggest that it does not lead to an increased burden of emergency department visits. Our population had high adherence rates, with the majority achieving maintenance dose and staying on this dose for one year.
MRI radiomics and nutritional-inflammatory biomarkers: a powerful combination for predicting progression-free survival in cervical cancer patients undergoing concurrent chemoradiotherapy
Authors: Yan Qi , Wu Menghan- , Zhang Jing , Yang Jiayang- , Lv Guannan- , Qu Baojun- , Zhang Yanping- , Yan Xia , Song Jianbo- 
Published: October 2024

Abstract
Objective
This study aims to develop and validate a predictive model that integrates clinical features, MRI radiomics, and nutritional-inflammatory biomarkers to forecast progression-free survival (PFS) in cervical cancer (CC) patients undergoing concurrent chemoradiotherapy (CCRT). The goal is to identify high-risk patients and guide personalized treatment.

Methods
We performed a retrospective analysis of 188 patients from two centers, divided into training (132) and validation (56) sets. Clinical data, systemic inflammatory markers, and immune-nutritional indices were collected. Radiomic features from three MRI sequences were extracted and selected for predictive value. We developed and evaluated five models incorporating clinical features, nutritional-inflammatory indicators, and radiomics using C-index. The best-performing model was used to create a nomogram, which was validated through ROC curves, calibration plots, and decision curve analysis (DCA).

Results
Model 5, which integrates clinical features, Systemic Immune-Inflammation Index (SII), Prognostic Nutritional Index (PNI), and MRI radiomics, showed the highest performance. It achieved a C-index of 0.833 (95% CI: 0.792–0.874) in the training set and 0.789 (95% CI: 0.679–0.899) in the validation set. The nomogram derived from Model 5 effectively stratified patients into risk groups, with AUCs of 0.833, 0.941, and 0.973 for 1-year, 3-year, and 5-year PFS in the training set, and 0.812, 0.940, and 0.944 in the validation set.

Conclusions
The integrated model combining clinical features, nutritional-inflammatory biomarkers, and radiomics offers a robust tool for predicting PFS in CC patients undergoing CCRT. The nomogram provides precise predictions, supporting its application in personalized patient management.
The lack of floater perception in eyes with asteroid hyalosis and its direct implications on laser vitreolysis
Authors: Zaher Elie , Blumenthal Yonatan , Blumenthal Eytan Z. 
Published: October 2024

Abstract
Purpose
To present a novel optical model explaining why the vast majority of patients with Asteroid Hyalosis (AH) do not perceive any floaters. This changes our understanding of floater perception and undermines the operation mode of YAG laser vitreolysis.

Methods
Relying on a previously published model of floater perception based on astronomical equations of a solar eclipse, and on ultrasound images of the vitreous in three eyes with AH, we explain why such patients do not perceive floaters in spite of opaque bodies filling their entire vitreous, to the point of, in severe cases of AH, obscuring the fundus view during ophthalmoscopy.

Main outcome measures
Developing an optical model of light rays that can quantify the maximal distance upon which a vitreous floater or opacity will cast a shadow on the retina.

Results
Calculations using the proposed model demonstrated that with a 3 mm pupil, for a floater located between 1.5 mm and 2 mm from the retina, its shortest diameter must be > 215 microns and > 286 microns, respectively, to be perceived. Since AH floaters, based on ultrasound imaging, do not exist in the most peripheral 1.5 mm of the vitreous, it becomes understandable why these patients are asymptomatic.

Conclusions
Based on the proposed model and our findings, we deduced that even large, degenerative floaters whose width is usually narrower than a large retinal vein (125 microns), must be located very close to the retina and hence are not the floaters that are aimed at when performing YAG laser vitreolysis. We speculate that in successful cases, YAG vitreolysis works by a different mechanism, most likely a shock wave that displaces floaters further away from the retina. Hence, vitreolysis might not necessarily require the laser be aimed at the floaters, as symptomatic floaters may be located in the outer 1.5–2.0 mm of the vitreous body, a very risky zone for YAG laser shots.
Characterization and Regulation of the Neonatal Growth Hormone Surge
Authors: Gusmao Daniela O , de Sousa Ligia M M , de Sousa Maria E , Rusew Stephanie J R , List Edward O , Kopchick John J , Gomes Andre F , Campideli-Santana Ana C , Szawka Raphael E , Donato Jose 
Published: October 2024

Abstract
High neonatal growth hormone (GH) secretion has been described in several species. However, the neuroendocrine mechanisms behind this surge remain unknown. Thus, the pattern of postnatal GH secretion was investigated in mice and rats. Blood GH levels were very high on postnatal day (P)1 and progressively decreased until near zero by P17 in C57BL/6 mice without sex differences. This pattern was similar to that observed in rats, except that female rats showed higher GH levels on P1 than males. In comparison, follicle-stimulating hormone exhibited higher secretion in females during the first 3 weeks of life. Hypothalamic Sst mRNA and somatostatin neuroendocrine terminals in the median eminence were higher in P20/P21 mice than in newborns. Knockout mice for GH-releasing hormone (GHRH) receptor showed no GH surge, whereas knockdown mice for the Sst gene displayed increased neonatal GH peak. Leptin deficiency caused only minor effects on early-life GH secretion. GH receptor ablation in neurons or the entire body did not affect neonatal GH secretion, but the subsequent reduction in blood GH levels was attenuated or prevented by these genetic manipulations, respectively. This phenotype was also observed in knockout mice for the insulin-like growth factor-1 (IGF-1) receptor in GHRH neurons. Moreover, glucose-induced hyperglycemia overstimulated GH secretion in neonatal mice. In conclusion, GH surge in the first days of life is not regulated by negative feedback loops. However, neonatal GH secretion requires GHRH receptor, and is modulated by somatostatin and blood glucose levels, suggesting that this surge is controlled by hypothalamic-pituitary communication.
The Impact of Exercise Intensity and Sex on Endogenous Ghrelin Levels and Appetite in Healthy Humans
Authors: Anderson Kara C , Mardian Tana , Stephenson Benjamin , Grammer Emily E , Stahl Macy E , Weeldreyer Nathan R , Liu Zhenqi , Love Kaitlin M , Kranz Sibylle , Allen Jason D , Weltman Arthur 
Published: October 2024

Abstract

Context
Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. Although acute exercise has been shown to modulate ghrelin levels, data on the impact of exercise intensity on AG and DAG levels and their effects on appetite are sparse and primarily limited to males.

Objective
To investigate the effect of exercise intensity and sex on ghrelin levels and appetite in untrained humans.

Methods
Eight males (age: 43.1 ± 10.9 years; body mass index [BMI]: 22.2 ± 1.7 kg/m2; peak oxygen consumption [VO2peak]: 36.3 ± 6.4 mL/kg/min) and 6 females (age: 32.2 ± 11.1 years; BMI: 22.7 ± 1.0 kg/m2; VO2peak: 29.2 ± 4.0 mL/kg/min) completed a maximal graded cycle ergometer lactate threshold (LT)/VO2peak test. These data were used to determine the exercise intensity on 3 subsequent randomized control or calorically matched cycle exercise bouts: (1) CON, no exercise; (2) MOD, the power output at LT; (3) HIGH, the power output associated with 75% of the difference between LT and VO2peak. Perception of appetite was analyzed using visual analog scales.

Results
Females had higher levels of total ghrelin (TG) (P = .03) and DAG (P = .01) at baseline than males. Both groups exhibited reduced DAG levels in HIGH compared with MOD and CON (P &lt; .0001-.004); however, only females had significantly reduced AG in HIGH (P &lt; .0001). Hunger scores were higher in MOD than in CON (P &lt; .01).

Conclusion
High-intensity may be superior to moderate-intensity exercise for reducing ghrelin levels and modifying hunger, and sex may impact this response.
Postoperative Morbidity and Factors Predicting the Development of Lymphoceles Following Lateral Pelvic Node Dissection for Rectal Cancer: A Cohort Study
Authors: Mathew Joseph , Kazi Mufaddal , Desouza Ashwin , Saklani Avanish 
Published: October 2024

Abstract
Purpose
Lateral pelvic node dissection (LPLND) is indicated in the surgical management of clinically significant pelvic lymphadenopathy associated with rectal malignancies. However, procedure-related morbidity, including the incidence and predisposing factors for lymphoceles arising in this setting have not been adequately evaluated.

Methods
This retrospective single-institution study included 183 patients with nonmetastatic, lateral node-positive rectal cancer undergoing total mesorectal excision with LPLND between June 2014 and May 2023 to determine the incidence and severity of postoperative complications using the Clavien-Dindo system, with logistic regression performed to model a relationship between lymphocele-development and potentially-predictive variables.

Results
In this cohort, mean age was 45.3 ± 12.81 years, 62.8% were male, and 27.9% had body mass index ≥ 25 kg/m2. Median tumor-distance from the verge was 3.0 (interquartile range [IQR] 1.0–5.0) cm. Following radiotherapy in 86.9%, all patients underwent surgery: 30.1% had open resection and 26.2% had bilateral LPLND. Median nodal-yield was 6 (IQR 4–8) per side. Postoperatively, 45.3% developed complications, with 18% considered clinically significant. Lymphoceles, detected in 21.3%, comprised the single-most common sequelae following LPLND, 46.2% arising within 30 days of surgery and 33.3% requiring intervention. On multivariate analyses, obesity (hazard ratio [HR] 2.496; 95% confidence interval [CI] 1.094–5.695), receipt of preoperative radiation (HR 10.026; 95% CI 1.225–82.027), open surgical approach (HR 2.779; 95% CI 1.202–6.425), and number of harvested nodes (HR 1.105; 95% CI 1.026–1.190) were significantly associated with lymphocele-development.

Conclusions
Pelvic lymphoceles and its attendant complications represent the most commonly encountered morbidity following LPLND for rectal cancer, with obesity, neoadjuvant radiotherapy, open surgery, and higher nodal-yield predisposing to their development.
Quality Improvement Spillovers: Evidence from the Hospital Readmissions Reduction Program
Authors: Soltani Mohamad , Batt Robert J. , Bavafa Hessam 
Published: October 2024

Quality knowledge spillovers can enhance the overall effectiveness of quality improvement initiatives. We study the presence and moderators of such spillovers in a multitask service setting, specifically in hospital inpatient care. Leveraging a national quality improvement regulation, the Hospital Readmissions Reduction Program (HRRP), which offers partial incentives for hospitals to reduce readmissions, we employ difference-in-differences econometric models on a nationwide database and find positive quality spillovers in the healthcare sector. Our findings indicate that the implementation of HRRP led to a significant decrease in 30-day readmissions among patients with clinical conditions or insurance types that were not targeted by the policy. Additionally, we find that task similarity played a positive role in promoting quality spillovers, while a hospital’s operational focus on target patients (i.e., the proportion of hospital volume targeted by the policy) did not moderate these spillovers. Notably, we observe that hospitals achieved these quality improvements without increasing the intensity of care provided, and that meaningful improvements in quality were associated with up to a 3% reduction in hospitalization costs. This paper contributes novel insights into how regulators and policymakers can design narrow public policies and regulations that achieve broader results by exploiting the beneficial quality improvement spillovers of partial incentives. This paper was accepted by Ranjani Krishnan, accounting. Funding: Support for this research was provided by the Alberta School of Business Faculty Seed Grant and the University of Wisconsin-Madison Office of the Vice Chancellor for Research and Graduate Education, with funding from the Wisconsin Alumni Research Foundation. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.01062 .