bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemodynamic gain index and heart failure incidence- Prognostic and preventive value
Authors: Vainshelboim Baruch , Myers Jonathan 
Published: July 2023

Abstract

Aims
Heart failure (HF) is a non-curable, life-threatening condition, characterized by impaired haemodynamic function and poor survival. This study aimed to assess the association between haemodynamic gain index (HGI) and HF incidence in men.

Methods and results
Exposure was HGI, [(HRpeak*SBPpeak) − (HRrest*SBPrest)]/(HRrest*SBPrest) measured from treadmill exercise testing in 5539 men aged 59 ± 11.5 years who were free from HF at baseline. The outcome was the incidence of HF. Cox hazard models adjusted for established risk factors were analysed for the association between HGI and HF. During 14.3 ± 6 years of follow-up, 297 cases of HF occurred (average annual incidence rate 3.7 events per 1000 person-years) and average HGI was 1.6 ± 0.7 bpm/mmHg. In a continuous model, every one unit higher in HGI was associated with a 44% [hazard ratio 0.56, 95% confidence interval (0.45–0.69), P &lt; 0.001] lower risk of HF incidence. In a categorical model, compared with those in quartile-4 (HGI &gt; 2.0), those in quartile-3 (HGI 1.51-2.0), quartile-2 (HGI 1.05-1.5), and quartile-1 (HGI &lt; 1.05) exhibited 70%, 220%, and 280% higher risks for developing HF, respectively (P trend &lt; 0.001).

Conclusion
HGI was found to be a strong predictor of HF incidence in men, supporting its prognostic value. Higher HGI was independently associated with lower risk of HF incidence, while low HGI could serve as a prognostic risk factor for HF. Integrating HGI in the screening and early detection paradigm and referring individuals with low HGI to exercise rehabilitation could potentially enhance public health and prevention strategies against HF.
Genetic variants in melanogenesis proteins TYRP1 and TYR are associated with the golden rhesus macaque phenotype
Authors: Peterson Samuel M , Watowich Marina M , Renner Lauren M , Martin Samantha , Offenberg Emma , Lea Amanda , Montague Michael J , Higham James P , Snyder-Mackler Noah , Neuringer Martha , Ferguson Betsy 
Published: July 2023

Abstract
Nonhuman primates (NHPs) are vital translational research models due to their high genetic, physiological, and anatomical homology with humans. The “golden” rhesus macaque (Macaca mulatta) phenotype is a naturally occurring, inherited trait with a visually distinct pigmentation pattern resulting in light blonde colored fur. Retinal imaging also reveals consistent hypopigmentation and occasional foveal hypoplasia. Here, we describe the use of genome-wide association in 2 distinct NHP populations to identify candidate variants in genes linked to the golden phenotype. Two missense variants were identified in the Tyrosinase-related protein 1 gene (Asp343Gly and Leu415Pro) that segregate with the phenotype. An additional and distinct association was also found with a Tyrosinase variant (His256Gln), indicating the light-colored fur phenotype can result from multiple genetic mechanisms. The implicated genes are related through their contribution to the melanogenesis pathway. Variants in these 2 genes are known to cause pigmentation phenotypes in other species and to be associated with oculocutaneous albinism in humans. The novel associations presented in this study will permit further investigations into the role these proteins and variants play in the melanogenesis pathway and model the effects of genetic hypopigmentation and altered melanogenesis in a naturally occurring nonhuman primate model.
Cefepime in vivo activity against carbapenem-resistant Enterobacterales that test as cefepime susceptible or susceptible-dose dependent in vitro: implications for clinical microbiology laboratory and clinicians
Authors: Fouad Aliaa , Gill Christian M , Simner Patricia J , Nicolau David P , Asempa Tomefa E 
Published: July 2023

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) are a public health concern. Among these isolates, there are reports of isolates that test as cefepime susceptible or susceptible-dose dependent (SDD) in vitro despite presence of a carbapenemase. This study aimed to evaluate the pharmacokinetic/pharmacodynamic profile of cefepime against carbapenemase-producing (CP-CRE) and non-producing (non-CP-CRE) isolates with a range of cefepime MICs.

Methods
Reference broth microdilution and modified carbapenem inactivation method (mCIM) were performed on genotypically characterized clinical CRE isolates. Ultimately, CP-CRE (n = 21; blaKPC) and non-CP-CRE (n = 19) isolates with a distribution of cefepime MICs (≤0.5 to &gt;256 mg/L) were utilized in the murine thigh infection model. Mice were treated with cefepime human-simulated regimens (HSRs) representative of a standard dose (1 g q12h 0.5 h infusion) or the SDD dose (2 g q8h 0.5 h infusion). Efficacy was assessed as the change in bacterial growth at 24 h compared with 0 h control, where ≥1 log bacterial reduction is considered translational value for clinical efficacy.

Results
Among both cohorts of CRE isolates, i.e. CP-CRE and non-CP-CRE, that tested as SDD to cefepime in vitro, 1 log bacterial reduction was not attainable with cefepime. Further blunting of cefepime efficacy was observed among CP-CRE isolates compared with non-CP-CRE across both susceptible and SDD categories.

Conclusions
Data indicate to avoid cefepime for the treatment of serious infections caused by CRE isolates that test as cefepime susceptible or SDD. Data also provide evidence that isolates with the same antibiotic MIC may have different pharmacokinetic/pharmacodynamic profiles due to their antimicrobial resistance mechanism.
Current prognostic factors of advanced gastric cancer patients treated with chemotherapy: real world data from a Japanese 12 institutions
Authors: Yamamoto Shumpei , Kanzaki Hiromitsu , Sakaguchi Chihiro , Mouri Hirokazu , Tsuzuki Takao , Nasu Junichiro , Kobayashi Sayo , Toyokawa Tatsuya , Obayashi Yuka , Inoue Masafumi , Kato Ryo , Matsubara Minoru , Kita Masahide , Okada Hiroyuki 
Published: July 2023

Abstract

Background
Understanding the prognostic factors of advanced gastric cancer before starting chemotherapy is important to determine personalized treatment strategies. However, the details of chemotherapy and the prognosis of advanced gastric cancer patients have changed with the time and environment. The aim of this study was to understand the current reality of chemotherapy and to estimate the prognostic factors of advanced gastric cancer patients before starting chemotherapy at multiple centers. This includes specialized cancer hospitals and community hospitals, with the latest data under the Japanese insurance system.

Methods
We evaluated the clinical parameters and treatment details of 1025 patients who received systemic chemotherapy for unresectable advanced gastric cancer from 2012 to 2018 at 12 institutions in Japan. Prognostic factors were analyzed using the Cox proportional hazards regression model.

Results
As of April 2021, 953 (93%) patients had died, while 72 (7%) patients survived. The median overall survival and progression-free survival of first-line chemotherapy was 11.8 months (95% confidence interval, 10.8–12.3 months) and 6.3 months (95% confidence interval, 5.9–6.9 months), respectively. Multivariate analysis revealed eight prognostic factors: age &lt; 40 years, performance status ≥2, no gastrectomy, diffuse histological type, albumin &lt;3.6, alkaline phosphatase ≥300, creatinine ≥1.0 and neutrophil-to-lymphocyte ratio &gt; 3.0. Patients using trastuzumab showed better survival than patients without (16.1 months vs. 11.1 months; P = 0.0005).

Conclusions
We identified eight prognostic factors for patients with advanced gastric cancer undergoing Japanese standard chemotherapy. Our results will help clinicians develop treatment strategies for every patient.
Strigolactones promote the localization of the ABA exporter ABCG25 at the plasma membrane in root epidermal cells of Arabidopsis thaliana
Authors: Russo Giulia , Capitanio Serena , Trasoletti Marta , Morabito Cristina , Korwin Krukowski Paolo , Visentin Ivan , Genre Andrea , Schubert Andrea , Cardinale Francesca 
Published: July 2023

Abstract
The phytohormones strigolactones crosstalk with abscisic acid (ABA) in acclimation to osmotic stress, as ascertained in leaves. However, our knowledge about underground tissues is limited, and lacking in Arabidopsis: whether strigolactones affect ABA transport across plasma membranes has never been addressed. We evaluated the effect of strigolactones on the localization of ATP BINDING CASSETTE G25 (ABCG25), an ABA exporter in Arabidopsis thaliana. Wild-type, strigolactone-insensitive, and strigolactone-depleted seedlings expressing a green fluorescent protein:ABCG25 construct were treated with ABA or strigolactones, and green fluorescent protein was quantified by confocal microscopy in different subcellular compartments of epidermal root cells. We show that strigolactones promote the localization of an ABA transporter at the plasma membrane by enhancing its endosomal recycling. Genotypes altered in strigolactone synthesis or perception are not impaired in ABCG25 recycling promotion by ABA, which acts downstream or independent of strigolactones in this respect. Additionally, we confirm that osmotic stress decreases strigolactone synthesis in A. thaliana root cells, and that this decrease may support local ABA retention under low water availability by allowing ABCG25 internalization. Thus, we propose a new mechanism for ABA homeostasis regulation in the context of osmotic stress acclimation: the fine-tuning by strigolactones of ABCG25 localization in root cells.
High-fat diet-induced obesity accelerates the progression of spontaneous osteoarthritis in senescence-accelerated mouse prone 8
Authors: Ding Chenyang , Yimiti Dilimulati , Sanada Yohei , Matsubara Yuki , Nakasa Tomoyuki , Matsubara Kiminori , Adachi Nobuo , Miyaki Shigeru 
Published: July 2023

ABSTRACT

Objectives
Ageing and obesity are major risk factors for osteoarthritis (OA), a widespread disease currently lacking efficient treatments. Senescence-accelerated mouse prone 8 (SAMP8) display early onset ageing phenotypes, including OA. This study investigates the impacts of high-fat diet (HFD)-induced obesity on OA development in SAMP8.

Methods
SAMP8 at 5 weeks were fed either a normal chow diet or an HFD for 10 weeks to induce obesity. Parameters related to obesity, liver function, and lipid and glucose metabolism were analysed. At 14 weeks of age, knee joint pathology, bone mineral density, and muscle strength were assessed. Immunohistochemistry and TUNEL staining were performed to evaluate markers for cartilage degeneration and chondrocyte apoptosis.

Results
At 14 weeks of age, HFD-induced obesity increased liver and adipose tissue inflammation in SAMP8 without further exacerbating diabetes. Histological scoring revealed aggravated cartilage, menisci deterioration, and synovitis, while no further loss of bone mineral density or muscle strength was observed. Increased chondrocyte apoptosis was detected in knee joints following HFD feeding.

Conclusions
Ten weeks of HFD feeding promotes spontaneous OA progression in 14-week-old SAMP8, potentially via liver damage that subsequently leads to chondrocyte apoptosis. This ageing-obese mouse model may prove valuable for further exploration of spontaneous OA pathophysiology.
Moderate coffee or tea consumption decreased the risk of cognitive disorders: an updated dose–response meta-analysis
Authors: Zhu Ying , Hu Chun-Xiang , Liu Xu , Zhu Rui-Xia , Wang Ben-Qiao 
Published: July 2023

Abstract

Context
Although several epidemiological studies have examined the association between coffee or tea intake and the risk of cognitive disorders, the results to date are inconsistent.

Objective
An updated systematic review and dose–response meta-analysis was conducted to confirm the association between coffee, tea, and caffeine consumption and the risk of cognitive disorders.

Data Sources
PubMed, Embase, and Web of Science were searched from inception to January 2022 for relevant studies, including dementia, Alzheimer disease (AD), and cognitive impairment or decline.

Data Extraction
Two reviewers independently performed data extraction and assessed the study quality.

Data Analysis
Restricted cubic splines were used to conduct the dose–response meta-analysis for coffee and tea intake.

Results
Twenty-two prospective studies and 11 case-control studies involving 389 505 participants were eligible for this meta-analysis. Coffee and tea consumption was linked to a lower risk of cognitive disorders, with an overall relative risk (RR) of 0.73 (95% CI: 0.60–0.86) and 0.68 (95% CI: 0.56–0.80), respectively. The subgroup analysis revealed that ethnicity, sex, and outcomes had significant effects on this association. Protection was stronger for men than that for women in both coffee and tea consumption. A nonlinear relationship was found between coffee consumption and AD risk, and the strength of protection peaked at approximately 2.5 cups/day (RR: 0.74; 95% CI: 0.59–0.93). A linear relationship was found between tea consumption and cognitive disorders, and the risk decreased by 11% for every 1-cup/day increment.

Conclusion
This meta-analysis demonstrated that the consumption of 2.5 cups coffee/day minimizes the risk of AD, and 1 cup/day of tea intake leads to an 11% reduction in cognitive deficits. Effective interventions involving coffee and tea intake might prevent the occurrence of dementia.
Career Satisfaction and Advancement Related to Mentorship Experiences of Underrepresented Nursing Faculty
Authors: Costa Christine B. , Smith Judy E. 
Published: July 2023

Abstract

AIM
This study aimed to describe the perceived impact of mentorship on career satisfaction and advancement for underrepresented nursing faculty.

BACKGROUND
Mentoring contributes to career development through a continuous learning process and support for role development.

METHOD
Fifteen underrepresented nurse faculty in academia comprised the sample for this qualitative phenomenological study.

RESULTS
Themes of career advancement and satisfaction related to mentorship included personal and professional growth, retention, lost opportunities, isolation, and multilayered mentoring.

CONCLUSION
Results of this study may be used to support the development of multilayered mentorship programs to meet the unique needs of underrepresented nurse faculty and improve diversity in nursing education.
URM: Underrepresented or Underrecognized? A Case Study of Black Pediatric Critical Care Physicians
Authors: Edwell April , Van Schaik Sandrijn , Teherani Arianne 
Published: July 2023

Purpose
This study explored Black physicians’ experience via an antideficit lens to gain new ideas for advancing minoritized physicians in academic medicine more broadly. Increasingly, systemic racism in academic medicine is intentionally acknowledged and named. However, many solutions to tackle racism and the overall paucity of Black physicians use a deficit framing, painting Black physicians and trainees as lacking preparation, interest, or experience and qualifications. Such solutions aim to help Black people assimilate into the “White Space” of academic medicine, rather than focusing on Black people’s strengths.

Method
This qualitative study included 15 Black physicians and trainees in pediatric critical care medicine (PCCM) from across the country who participated in semistructured interviews. Through an antideficit lens, the researchers examined the social, cultural, and structural contexts influencing the participants’ individual experiences. They analyzed the data combining thematic and narrative qualitative analysis approaches, including restorying.

Results
The data help promote understanding of the landscape and context in which Black PCCM physicians become successful. Achievement took on different forms for the participants. Participants described enablers of achievement that supported them through their individual journeys spanning 3 general domains—intrinsic, interpersonal, and systemic. Three additional enablers were tied specifically to participants’ Black identities—harnessing Blackness as a superpower, leaning in to lead, and successfully navigating the “unwritten rules.”

Conclusions
By using an antideficit framework, this study delineates and centers participants’ ingenuity in cultivating repertoires of practice that enabled them to succeed, despite challenges rooted in systemic racism. Going forward, rather than focus solely on what is missing, academic medicine should try to shift systems and regularly recognize and value the knowledge, expertise, and merit Black that physicians bring. Perhaps an appropriate framing is not that Black physicians are underrepresented in medicine; maybe instead, it is that they are underrecognized.
Assessment and Validation of Anterior Humeral Line for Diagnosing Supracondylar Humerus Fractures in the Pediatric Population
Authors: Yao Benjamin , Ko Justine , Maheshwer Bhargavi , Dumaine Anne M. , Nguyen Cynthia V. , Liu Raymond W. 
Published: July 2023

Introduction:
Pediatric supracondylar humerus fractures are commonly evaluated using the anterior humeral line (AHL) on a lateral radiograph. Rotational variations in radiographic projection are common due to child discomfort and could lead to changes in management based on where the AHL intersects the capitellum. The purpose of this study was to establish whether rotational variations in elbow rotation leads to significant changes in AHL position and whether drawing the AHL based on the distal humerus versus shaft is more tolerant to rotation.

Methods:
Fifty children with nonoperative supracondylar humerus fractures were identified with sub optimally positioned injury and well positioned follow-up lateral radiographs. The proportion of the bone anterior to the intersection of the AHL and the capitellum was measured using the humeral shaft versus distal humerus to guide position of the AHL. This process was repeated on ten pediatric humerus dry cadaveric specimens which were imaged in 5-degree rotational increments along the axis of the humeral shaft from −20 to +20 degrees.

Results:
AHL position correlated poorly when measured on rotated lateral radiographs of clinical patients versus non-rotated lateral radiographs when using the distal humerus as a guide (intraclass correlation coefficient 0.14), compared with when using the humeral shaft as a guide (intraclass correlation coefficient 0.81). When assessing the pediatric humerus dry cadavers between the 2 techniques, there was greater statistically significant variation in rotated positions compared with the neutral position in the distal humerus AHL measurement approach compared with the humeral shaft AHL measurement approach, with the mean AHL within the central third of the capitellum for more rotational positions when using the shaft compared with the distal humerus.

Conclusions:
With rotated lateral elbow radiographs in supracondylar humerus fractures, utilizing the humeral shaft provides more consistent AHL measurements than utilizing the distal humerus, and thus drawing the line starting at the shaft of the humerus is recommended for surgical decision making.
Analysis of Growth After Transphyseal Anterior Cruciate Ligament Reconstruction in Children
Authors: Bolzinger Manon , Thevenin Lemoine Camille , Flumian Clara , Nicolaou Nicolas , Sales de Gauzy Jerome , Accadbled Franck 
Published: July 2023

Background:
Pediatric transphyseal anterior cruciate ligament reconstruction (ACLR) bears several advantages and is widely used. The main concern is the risk of growth disturbance. Our purpose was to investigate the incidence and risk factors of growth disturbance in skeletally immature patients who underwent transphyseal ACLR. We hypothesized that this procedure would generate neither clinically relevant limb length discrepancy (LLD) nor axis deviation.

Methods:
This prospective, consecutive, single-center series included skeletally immature patients who underwent primary transphyseal ACLR using semitendinosus tendon autograft, with a 2-year follow-up bone length standing radiograph of both lower limbs from pelvis to ankle in anterior posterior view. Lower limb length, mechanical axis deviation (MAD), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. The definition of postoperative growth disturbance was defined as ≥10 mm for LLD or ≥3 degrees for axis deviation in comparison to the contralateral lower limb. Predictive variables included age at surgery, gender, side, and diameter of bone tunnels. Student or Mann-Whitney test was used for numerical variables, and Chi-square test or Fisher exact test was used for categorical variables. P values <0.05 were considered statistically significant.

Results:
Fifty consecutively treated patients were included. Forty-seven patients (31 boys, 16 girls) with a mean age of 13.2 years (range, 9 to 16) at the time of surgery were available for analysis. Six patients had an LLD of at least 10 mm. Twenty-five patients had a difference in MPTA of a least 3 degrees (range, 5 to 8). Sixteen patients had a difference in LDFA of a least 3 degrees (range, 4 to 9). No patients presented with a clinical deformity or related symptoms. Regarding coronal alignment, there was no statistical difference in mechanical axis deviation, LDFA, or MPTA. Gender, side, age, and bone tunnel diameter did not influence growth disturbance.

Conclusions:
Transphyseal pediatric ACLR generated a high rate of growth disturbances (leg length discrepancy and axis deviation) although none clinically relevant. Mild proximal tibial axis deviation in patients operated on near skeletal maturity should be further investigated.

Level of Evidence:
Level III.

Study design:
Case-control study.
Rate of Retinal Nerve Fiber Layer Thinning in Glaucomatous Eyes With Optic Disc and Parapapillary Deep-Layer Microvasculature Loss
Authors: Lee Anna , Sung Kyung Rim , Kim Joon Mo , Lee Jin Yeong , Rim Hyunah 
Published: July 2023

Précis:
Microvasculature dropout in the parapapillary choroidal layer was a more important biomarker of glaucomatous nerve fiber layer thinning when it presented with deep-layer microvasculature of the optic disc rather than when it presents by itself.

Purpose:
To characterize open angle glaucoma eyes with optic nerve head deep-layer microvasculature dropout (MvD-D) and parapapillary choroidal layer microvasculature dropout (MvD-P) and compare their retinal nerve fiber layer (RNFL) thinning rate.

Material and Methods:
This study included 122 open angle glaucoma eyes that underwent ≥5 serial spectral-domain optical coherence tomography scans during a mean follow-up of 5.4 years. Swept-source optical coherence tomography angiography was used to evaluate MvD-P and MvD-D. Subjects were classified into 3 groups according to the presence of MvD-P and MvD-D: (1) no dropout (n=37); (2) solely MvD-P (n=40), and (3) both MvD-P and MvD-D (n=45). The RNFL thinning rate was compared among the 3 groups, and the associated factors were assessed by Cox proportional hazard analysis.

Results:
RNFL thinning rates were highest in the group with both MvD-P and MvD-D, followed by the group with solely MvD-P and finally by the no dropout group (−0.24 vs. −0.65 vs. −1.20 μm/y, P<0.001). Thinner central corneal thickness [hazard ratio (HR)0.990, P=0.003], presence of disc hemorrhage (HR=1.802, P=0.035), and coexistence of MvD-P and MvD-D (HR=2.941, P<0.001) were the factors associated with RNFL thinning.

Conclusions:
The coexistence of MvD-P and MvD-D was associated with faster RNFL thinning than MvD-P alone or no dropout, which suggested that observing the optic disc deep microvasculature along with parapapillary choroidal layer using Swept-source optical coherence tomography angiography may be clinically relevant in monitoring glaucoma progression.