bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human wild‐type andD76Nβ2‐microglobulin variants are significant proteotoxic and metabolic stressors for transgenicC. elegans
Authors: Raimondi Sara , Faravelli Giulia , Nocerino Paola , Mondani Valentina , Baruffaldi Alma , Marchese Loredana , Mimmi Maria Chiara , Canetti Diana , Verona Guglielmo , Caterino Marianna , Ruoppolo Margherita , Mangione P. Patrizia , Bellotti Vittorio , Lavatelli Francesca , Giorgetti Sofia 
Published: October 2023

Abstractβ2‐microglobulin (β2‐m) is a plasma protein derived from physiological shedding of the class I major histocompatibility complex (MHCI), causing human systemic amyloidosis either due to persistently high concentrations of the wild‐type (WT) protein in hemodialyzed patients, or in presence of mutations, such as D76N β2‐m, which favor protein deposition in the adulthood, despite normal plasma levels. Here we describe a new transgenic Caenorhabditis elegans (C. elegans) strain expressing human WT β2‐m at high concentrations, mimicking the condition that underlies dialysis‐related amyloidosis (DRA) and we compare it to a previously established strain expressing the highly amyloidogenic D76N β2‐m at lower concentrations. Both strains exhibit behavioral defects, the severity of which correlates with β2‐m levels rather than with the presence of mutations, being more pronounced in WT β2‐m worms. β2‐m expression also has a deep impact on the nematodes' proteomic and metabolic profiles. Most significantly affected processes include protein degradation and stress response, amino acids metabolism, and bioenergetics. Molecular alterations are more pronounced in worms expressing WT β2‐m at high concentration compared to D76N β2‐m worms. Altogether, these data show that β2‐m is a proteotoxic protein in vivo also in its wild‐type form, and that concentration plays a key role in modulating pathogenicity. Our transgenic nematodes recapitulate the distinctive features subtending DRA compared to hereditary β2‐m amyloidosis (high levels of non‐mutated β2‐m vs. normal levels of variant β2‐m) and provide important clues on the molecular bases of these human diseases.
Better Mobility Is Associated With Higher Incomes and Longer Working Years Among Older Adults
Authors: Pu Alex , Paul Subrata , Luke Brian , Bhattacharyya Timothy 
Published: October 2023

Abstract

Background
Robust physical mobility is the key to healthy independent aging. Although the association between socioeconomic status and health is well documented, it is unclear whether there is a relationship between mobility and income, because income data are not readily available.

Questions/purposes
(1) Do individuals with better mobility have higher incomes? (2) Does maintaining mobility over time allow individuals to keep working? (3) Is exercise associated with higher mobility over time?

Methods
We obtained longitudinal income and health data from the nationally representative Health and Retirement Study. Three cohorts were used. First, we studied the relationship between household income and mobility (on a 6-point index of walking impairment) in 19,430 adults who were assessed in 2016 (representing 93% of the 20,805-person total cohort). We measured the association of mobility and household income in a multivariate linear regression analysis of age, gender, health conditions, and education. We then identified a second group of 1094 individuals with unrestricted mobility in the year 2000 and compared differences in income and working rates between those who maintained mobility and those who lost mobility after 10 years. Finally, we identified a third group of 7063 individuals who were 60 to 80 years old in 2012, divided the group by how often they engaged in exercise, and observed differences in mobility after 4 years.

Results
After adjusting for covariates, a drop of one level of mobility was associated with a USD 3410 reduction in annual household income (95% CI USD 2890 to USD 3920; p < 0.001). After 10 years, individuals who maintained their mobility had incomes that were USD 6500 higher than that of individuals who were not working (95% CI USD 2300 to USD 10,300; p < 0.001) and were more likely to be working (40% versus 34.5%; p < 0.001). Exercising at least once per week was associated with better mobility 4 years later (mobility score 4.46 ± 0.08 versus 3.66 ± 0.08; p < 0.001).

Conclusion
Better mobility was associated with more than USD 3000 in annual income. Regular exercise and other interventions that improve mobility may have meaningful returns on investment.

Clinical Relevance
Because greater mobility is strongly associated with higher income, orthopaedic interventions may be undervalued.
The Impact of Prolonged Operative Time Associated with Minimally Invasive Colorectal Surgery: A Report from the Surgical Care Outcomes Assessment Program
Authors: Unruh Kenley R. , Bastawrous Amir L. , Kanneganti Shalini , Kaplan Jennifer A. , Moonka Ravi , Rashidi Laila , Sillah Arthur , Simianu Vlad V. 
Published: October 2023

BACKGROUND:
Increased operative time in colorectal surgery is associated with worse surgical outcomes. Laparoscopic and robotic operations have improved outcomes, despite longer operative times. Further, the definition of “prolonged” operative time has not been consistently defined.

OBJECTIVE:
The first objective was to define prolonged operative time across multiple colorectal operations and surgical approaches. The second was to describe the impact of prolonged operative time on length of stay and short-term outcomes.

DESIGN:
Retrospective-cohort study.

SETTING:
Forty-two hospitals in the Surgical Care Outcomes Assessment Program from 2011-2019

PATIENTS:
There were a total of 23,098 adult patients (age 18 years and older), undergoing 6 common, elective colorectal operations: right colectomy, left/sigmoid colectomy, total colectomy, low anterior resection, ileal-pouch anal anastomosis, or abdominoperineal resection.

MAIN OUTCOME MEASURES:
Prolonged operative time defined as the 75th quartile of operative times for each operation and approach. Outcomes were length of stay, discharge home, and complications. Adjusted models were used to account for factors that could impact both operative time and outcomes across the strata of open and minimally invasive approaches.

RESULTS:
Prolonged operative time was associated with longer median length of stay (7 vs. 5 days open, 5 vs. 4 days laparoscopic, 4 vs. 3 days robotic), more frequent complications (42% vs. 28% open, 24% vs. 17% laparoscopic, 27% vs. 13% robotic), but similar discharge home (86% vs. 87% open, 94% vs. 94% laparoscopic, 93% vs. 96% robotic). After adjustment, each additional hour of operative time above the median for a given operation was associated with 1.08 (1.06, 1.09) relative risk of longer length of stay for open operations and 1.07 (1.06, 1.09) relative risk for minimally invasive operations.

LIMITATIONS:
Our study was limited by being retrospective, resulting in selection bias, possible confounders for prolonged operative time, and lack of statistical power for subgroup analyses.

CONCLUSIONS:
Operative time has consistent overlap across surgical approaches. Prolonged operative time is associated with longer length of stay and higher probability of complications, but this negative effect is diminished with minimally invasive approaches..
Surveillance and Management of Pouch Neoplasia in Familial Adenomatous Polyposis: A Systematic Review
Authors: Gilad Ophir , Tulchinsky Hagit , Kariv Revital 
Published: October 2023

BACKGROUND:
Patients with familial adenomatous polyposis often require prophylactic colectomy with ileal pouch-anal anastomosis to treat and/or reduce to risk of colorectal neoplasia. However, after surgery, patients are still at some risk of developing pouch polyps and even cancer in both handsewn or stapled anastomoses. Management relies mainly on endoscopic or surgical interventions, while chemopreventive agents have a limited role in the management and prevention of pouch neoplasia. Novel endoscopic techniques are evolving and may gradually overtake surgical intervention in selected cases. Since familial adenomatous polyposis is relatively rare, there is scarcity of data regarding the natural history of pouch polyps and cancer in this population.

OBJECTIVE:
This systematic literature review aims to describe the evolution, characteristics, various treatment modalities and their outcomes as well as recommended surveillance strategies of pouch neoplasia.

DATA SOURCES:
PubMed and Cochrane databases, the international pouch consortium (for expert opinion).

STUDY SELECTION:
Studies between 1990 and 2023, in English were included. Studies reporting neoplastic outcomes of inflammatory bowel disease pouch patients only were excluded.

MAIN OUTCOME MEASURES:
Incidence of pouch neoplasia and its outcomes (successful resections, surgical complications, mortality).

RESULTS:
Thirty-five studies were included.

LIMITATIONS:
Most studies focus on inflammatory bowel diseases pouch patients, there is scarce data regarding polyposis patients only. Most cohorts are small and retrospective. Data on interventions is mainly descriptive and no randomized controlled trials are available.

CONCLUSIONS:
Pouch adenoma are common and well managed by endoscopic resections, as advanced-endoscopic techniques are becoming more available. Additional data are required for defining updated recommendations for either endoscopic or surgical intervention. Pouch cancer is a very rare event and may arise despite surveillance. Continued endoscopic surveillance is key in cancer prevention and early detection. Outcome of cancer cases is poor and management in a referral center should be advised with tumor board discussions.
Effects of Mindfulness-Based Interventions on Cardiometabolic-Related Adverse Pregnancy Outcomes
Authors: Root Andrea L. , Crossley Nicole P. , Heck Jennifer L. , McCage Shondra , Proulx Jeffrey , Jones Emily J. 
Published: October 2023

Background
Growing evidence suggests maternal stress contributes to the development of adverse pregnancy outcomes that are associated with cardiovascular and cardiometabolic risk in birthing persons. Mindfulness-based interventions may positively affect psychological stress in pregnancy and, in turn, reduce stress. However, few study authors have examined the effects of mindfulness-based interventions on adverse pregnancy outcomes that heighten cardiovascular risk.

Objective
The aim of this study was to appraise available literature examining the effects of mindfulness-based interventions delivered during pregnancy on adverse pregnancy outcomes associated with future cardiovascular and cardiometabolic disease risk.

Methods
In this systematic review, multiple electronic databases were searched using major keywords, including “mindfulness-based intervention,” “pregnancy,” “preterm delivery,” “gestational diabetes,” “small for gestational age,” “preeclampsia,” and “hypertension in pregnancy” during February 2023.

Results
Six studies using mindfulness-based interventions during pregnancy were included. The review indicated that these interventions were largely effective at reducing prenatal stress; however, the overall effects of interventions were mixed concerning their impact on pregnancy complications. Study authors examining the effects on gestational diabetes–related outcomes reported significant improvements in blood glucose levels, hemoglobin A1c, and oral glucose tolerance. Outcomes were mixed or inconclusive related to the effects of interventions on the incidence of preterm birth, birth of a small-for-gestational-age newborn, and preeclampsia.

Conclusions
Mitigating cardiovascular and cardiometabolic risk-associated adverse pregnancy outcomes through mindfulness-based approaches may represent an emerging field of study. The few studies and limited, mixed findings synthesized in this review indicate that high-validity studies are warranted to examine the effects of mindfulness-based interventions on pregnancy complications that contribute to cardiovascular-related maternal morbidity and suboptimal life course health for diverse birthing persons.
Physician Assistant Gender Differences in Research, Professional Goals, and Perceptions of Support
Authors: Lolar Sara , Welch Robert D. , Garino Alexandria 
Published: October 2023

Purpose
The majority of Physician assistant (PA) educators are women, yet men proportionately publish more and advance further in academic rank. This study examined if research interest, promotion goals, and perceptions of institutional support differed between PA educators with different gender identities.

Methods
This is a subset analysis of a previously published cross-sectional study. PA programs were stratified by region and Carnegie classification and were sampled by a stratified random sampling method. PA faculty from selected programs were invited to participate in an anonymous survey. Data were analyzed to account for the stratified sample design. Means and proportions with associated 95% confidence intervals are described.

Results
There was a 51% response rate (N = 110). Sixty-three percent of respondents identified as female and 36% as male. Men had a mean of 5.67 (0.17, 11.16) career research articles and women had 1.56 (0.68, 2.44) articles. Fifteen percent (3.7%, 26.3%) of men were full professor compared to 4.3% (0, 9.1%) of women. When transitioning to a faculty role, 72.5% (58.4%, 86.6%) of men and 52.9% (41%, 64.7%) of women felt supported by their institution. Both genders valued promotion, but 80% (67.6%, 92.4%) of men reported having clear 5-year goals compared to 58.8% (46.6%, 71%) of women (P = .034).

Conclusion
There was no statistical difference in publications between men and women in this study. Women felt less supported when transitioning to a faculty role compared to men. Both men and women valued promotion equally, but men reported working towards that goal more intentionally. This study found few consistent differences in the attitudes and behaviors towards scholarship between men and women.
Oral Health Care Strategies in Rural Communities: A Case Study
Authors: McCarthy Maren , Van Hook Maureen , Dereczyk Amy , Shaw-Gallagher Marlene 
Published: October 2023

Abstract
Dental caries affect 97% of the world’s population during their lifetime. Early childhood caries are the number one chronic disease affecting young children, and it disproportionately affects children of low-income families. American Academy of Pediatrics recommends fluoridated toothpaste to all children starting at tooth eruption, regardless of caries risk. In addition, fluoride varnish is recommended in all children every 3 to 6 months from tooth emergence until they have an established dental home. The health disparities that are most apparent in the rural communities are inadequate prenatal care, low birth weight, cancer, chronic respiratory disease, heart disease, unintentional injury, and stroke. When it comes to oral health, water fluoridation is one of the most cost-effective strategies in preventing dental caries. The need for oral health education in physician assistant/associate (PA) programs is well documented. Implementation has largely been performed using interprofessional education. This article describes an interprofessional education program that teaches PA students to apply fluoride varnish so that they are practice-ready when they graduate and practice medicine.
Psychosocial Issues in Sickle Cell Disease: A Review
Authors: Essien Emmanuel Aniekan , Winter-Eteng Blessing F. , Onukogu Chinyere Uchechi , Nkangha Dominic Dennis , Daniel Faithful 
Published: October 2023

<p> </p>
<p><strong>Abstract </strong></p>
<p>Sickle cell anaemia (SCA) is a severe sickle cell disease primarily affecting black populations and individuals in tropical countries. This condition causes significant morbidity and mortality and leads to various psychosocial challenges. Using a narrative review approach, this paper analysed 80 peer-reviewed articles published between 1989 and 2023 to understand these challenges comprehensively. Mental disorders, sleep disturbances, interpersonal relationship challenges, stigmatisation, and workplace discrimination significantly contributed to the psychosocial distress experienced by individuals with SCA and their families. Depression and anxiety were prevalent among individuals with SCA, leading to poor treatment adherence, increased pain, and disruptions in various aspects of life. Sleep disturbances, including sleep-disordered breathing and sleepwalking, were also significant contributors to poor sleep quality in SCA patients. Families of individuals with SCA also face challenges, including psychological stress, financial strain, and social disruption. Stigmatisation is common, leading to misconceptions and discrimination. Workplace discrimination is prevalent, with a high unemployment rate among adult SCA patients. Comprehensive care is crucial to address these psychosocial issues. Early identification and intervention, comprehensive support programs, patient and family education, enhanced pain management strategies, and integration of mental health into clinical care are recommended. School-based support, research and advocacy, and community support groups are also necessary. By addressing these challenges through comprehensive care and support, healthcare professionals, policymakers, and society can reduce psychosocial distress and improve the lives of individuals with Sickle cell anaemia.</p>
MiR-155 promotes acute organ injury in LPS-induced endotoxemic mice by enhancing CCL-2 expression in macrophages
Authors: Wang Chun , Zheng Yuxuan , Fan Qingting , Li Zilüe , Qi Xin , Chen Fanyan , Xu Lei , Zhou Sha , Chen Xiaojun , Li Yalin , Zhu Jifeng , Su Chuan 
Published: October 2023

Abstract
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Macrophages play important roles in the inflammatory process of sepsis by secreting chemokines. Chemokine (CC-motif) ligand 2 (CCL-2) is one of the main pro-inflammatory chemokines secreted by macrophages that plays a critical role in the recruitment of more monocytes and macrophages to the sites of injury in sepsis, but the mechanisms that regulate CCL-2 expression in macrophages during sepsis are still unknown. In the present study, by using the lipopolysaccharide (LPS)-induced endotoxemia model, we found that LPS induced the expression of microRNA (miR)-155 and CCL-2 in endotoxemic mice and RAW264.7 cells. MiR-155 mimics or miR-155 inhibitor treatment experiment suggested that miR-155 was sufficient to increase LPS-induced CCL-2 expression in macrophages, but miR-155 was not the only factor promoting CCL-2 expression. We further demonstrated that miR-155-induced increase of CCL-2 promoted chemotaxis of additional macrophages, which subsequently enhanced lung injury in endotoxemic mice. Serum/glucocorticoid regulated kinase family member 3 (SGK3), a potential target of miR-155, was identified by RNA sequencing and predicted by TargetScan and miRDB. We further confirmed miR-155 regulated SGK3 to increase LPS-induced CCL-2 by using miR-155 mimics and SGK3 overexpression. Thus, our study demonstrates that miR-155 targets SGK3 to increase LPS-induced CCL-2 expression in macrophages, which promotes macrophage chemotaxis and enhances organs injury during endotoxemia. Our study contributed to a better understanding of the mechanisms underlying the inflammatory response during sepsis.
Deciphering gut microbiota in patients with severe sepsis and septic shock
Authors: Lee Se Ju , Kim Dajeong , Ann Hea Won , Han Min , Lee Jung Ah , Lee Yongseop , Ahn Sangmin , Seo Hwi Won , Kim Jung Ho , Ahn Jin Young , Jeong Su Jin , Ku Nam Su , Yeom Joon-Sup , Ryu Choong-Min , Choi Jun Yong 
Published: October 2023

Abstract

Introduction
Gut microbiota dysbiosis is associated with susceptibility to sepsis and poor outcomes. However, changes to the intestinal microbiota during sepsis and their value as biomarkers are unclear. In this study, we compared the intestinal microbiota of patients with sepsis and healthy controls.

Methods
Stool was collected from patients with sepsis (subdivided according to mortality) and controls. Microbiome diversity and composition were analyzed by 16S rRNA gene pyrosequencing. The α-diversity of the intestinal microbiome was determined using operational taxonomic unit (OTU) counts and the Chao1, Shannon, and ACE indices. Adjusted Cox regression analyses assessed 6-month mortality risk factors.

Results
Fifty-nine patients (14 in-hospital deaths) and 29 healthy controls were enrolled. OTU counts and Chao1 and ACE indices were lower in the non-survivor than in the other groups. The controls showed a higher Shannon and lower Simpson index than did the sepsis group. The genus Blautia was more abundant in controls than in the sepsis group, and Faecalibacterium less abundant in the non-survivor than in the other groups. Regression analysis associated low Shannon index with 6-month mortality.

Conclusions
Survivors of sepsis, non-survivors, and healthy controls have different gut microbiomes, and a low Shannon index is a risk factor for 6-month mortality.
ANALYSIS AND IDENTIFICATION OF FERROPTOSIS-RELATED GENE SIGNATURE FOR ACUTE LUNG INJURY
Authors: Wang Jing , Yue Xiao-Qi , Li Yu-Ting , Jiang Miao , Liu Jun-Chao , Zhao Zi-Gang , Niu Chun-Yu 
Published: October 2023

ABSTRACTBackground:Recent studies have shown that ferroptosis is involved in the evolution of acute lung injury (ALI), a serious respiratory pathological process leading to death. However, the regulatory mechanisms underlying ferroptosis in ALI remain largely unknown. The current study analyzed and identified a ferroptosis-related gene signature for ALI.Methods:Key genes associated with ferroptosis in ALI were identified by bioinformatics analysis. GSE104214, GSE18341, and GSE17355 datasets were downloaded from the Gene Expression Omnibus database. The signature genes were screened by least absolute shrinkage and selection operator regression, and the key genes of ALI were screened by weighted correlation network analysis (WGCNA), followed by immune infiltration analysis and functional enrichment analysis. In addition, mRNA expression of key genes in the lungs of mice with hemorrhagic shock (HS) and sepsis was verified.Results:A total of 2,132 differential genes were identified by various analyses, and 9 characteristic genes were detected using Lasso regression. We intersected nine signature genes with WGCNA module genes and finally determined four key genes (PROK2,IL6,TNF,SLC7A11). All four key genes were closely correlated with immune cells and regulatory genes of ALI, and the expression of the four genes was significantly different in the lung tissues of HS and sepsis models. Besides, the ferroptosis-related molecules GPX4 and ACSL4 showed remarkable difference in these models.Conclusion:These results indicate thatPROK2,IL6,TNF, andSLC7A11may be key regulatory targets of ferroptosis during ALI. This study proved that ferroptosis is a common pathophysiological process in three ALI models.