bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of thoracoscopic-guided intercostal nerve block and ultrasound-guided intercostal nerve block in postoperative analgesia of uniportal video-assisted lobectomy: a pilot randomized controlled trial
Authors: Li Yan , Wei Luyao , Du Jian-Hui , He Jin-Xian , Xu Xia , Hu Li-Hong
Published: December 2024

Background:

Ultrasound-guided intercostal nerve block (UINB) and thoracoscopic-guided intercostal nerve block (TINB) are often used for analgesia after thoracic surgery. Herein, we compared the application of TINB and UINB for analgesia after uniportal video-assisted lobectomy.

Methods:

Sixty patients were randomly allocated into two groups: UINB and TINB. The surgical time of intercostal nerve block (INB), the success rate of the first needle, visual analog scale (VAS) scores, the time of the first patient-controlled intravenous analgesia (PCIA) press, the time for removing the thoracic drainage tube, consumption of sufentanil and the number of PCIA presses within 24 hours postoperatively, and adverse reactions (ARs) were compared between the two groups.

Results:

The surgical time of INB was significantly shorter in the TINB group than in the UINB group (P < 0.001). The time of the first press of PCIA was significantly earlier in the TINB group than in the UINB group (P < 0.001). The success rate of the first needle was significantly higher in the TINB group than in the UINB group (P < 0.001). No significant differences were observed between the two groups regarding VAS scores, time for removing the thoracic drainage tube, the consumption of sufentanil, the number of PCIA presses within 24 hours postoperatively, and ARs.

Conclusion:

TINB and UINB have similar analgesic effects after uniportal video-assisted lobectomy. However, TINB demonstrates shorter surgical time and a higher success rate than UINB.
Advances in theories and models of cardiac rehabilitation after acute myocardial infarction: A narrative review
Authors: Liu Jia , Zhao Qiannan , Shen Qianqian , Meng Xiaoqin , Zheng Yi , Lu Chen , Zheng Yeping
Published: December 2024

Acute myocardial infarction (AMI) remains a leading cause of mortality and disability worldwide, with its high mortality and recurrence rates significantly impacting patients’ quality of life and prognosis. Cardiac rehabilitation, as a comprehensive intervention strategy, plays a crucial role in improving outcomes for AMI patients. The aims to comprehensively analyze and evaluate the theoretical foundations and practical models of cardiac rehabilitation following AMI, providing healthcare professionals with up-to-date research advances and practical guidance. We systematically searched databases including PubMed, Web of Science, and Cochrane Library for relevant literature published between 2010 and 2023, selecting and analyzing high-quality studies related to theories and models of cardiac rehabilitation after AMI. This review elaborates on 7 major theories and models of cardiac rehabilitation, including the transtheoretical model, information-motivation-behavioral skills model, and self-determination theory. Analysis indicates that these theories and models have positive effects on improving patients’ quality of life, enhancing treatment adherence, and reducing rehospitalization rates. However, the applicability of different theories and models varies across cultural backgrounds and healthcare systems. Significant progress has been made in the research of theories and models for cardiac rehabilitation after AMI. However, further large-scale, multi-center studies are needed to validate their long-term effectiveness. Future research should focus on integrating these theories and models with emerging technologies to enhance the accessibility and efficacy of cardiac rehabilitation.
Dietary salt intake is not associated with risk of stroke: A Mendelian randomization study
Authors: Zhang Xiaomei , Tan Ruirui , Jia Xinyan , Wu Xingquan , Sun Hongdong , Xue Liyuan , Qi Chenxi , Yang Yonggang , Wang Zhaohui
Published: December 2024

Previous studies have demonstrated a correlation between dietary salt intake and stroke; however, there was a lack of conclusive evidence regarding a causal connection between them. We undertook a two-sample Mendelian randomization (MR) study to examine their potential association. The genome-wide data for dietary salt intake was sourced from genome-wide association study that involved 462,630 samples. Genetic instruments for stroke were also obtained from genome-wide association study, which included 446,696 samples. Both samples were from European. The inverse variance weighting was used as the main method in MR analysis. We also performed several complementary MR methods, including MR-Egger, position weighted median, simple model, and weighted model. Our results showed that there was no causal relationship between dietary salt intake and stroke, which was genetically determined (fixed-effects inverse variance weighted: odds ratio, 0.95; 95% confidence interval, 0.74–1.21; P 
= .67). Neither Cochran Q test (P = .52) nor MR-Egger method (P = .48) found obvious heterogeneity; in addition, the MR pleiotropy residual sum and outliers global test (P = .52) and MR-Egger regression intercept (P = .74) also showed no pleiotropy. The result of our MR study showed that there was no direct causal relationship between dietary salt intake and stroke risk. More studies were required to further confirm the stability of this relationship and to trying applied the findings to the clinic.
S100A11 is a potential prognostic biomarker and correlated with tumor immunosuppressive microenvironment in glioma
Authors: Fan Jikang , Wang Xuya , Yang Xuejun
Published: December 2024

Background:

This study investigates the role of S100A11 as a potential biomarker for glioma-associated macrophages (GAMs) and its correlation with GAMs infiltration in glioblastoma multiforme, aiming to better understand the immune microenvironment of glioma.

Methods:

We conducted a comprehensive study using various techniques and approaches. First, we examined the expression of S100A11 on GAMs through Western blot, immunohistochemistry, and immunofluorescence analyses. Additionally, we utilized single-cell sequencing data and immune infiltration analysis to establish the relationship between S100A11 and GAMs infiltration in glioma.

Results:

Our findings revealed that S100A11 was highly expressed on GAMs, as validated by Western blot, immunohistochemistry, and immunofluorescence. Moreover, S100A11 exhibited a strong correlation with GAMs infiltration, as evidenced by single-cell data and immune infiltration analysis. These results highlight the significant association of S100A11 with the immune microenvironment surrounding glioma.

Conclusion:

S100A11 emerges as a promising candidate for regulating glioma immunosuppression and may serve as a potential marker for GAMs. This study sheds light on the crucial role of S100A11 in the crosstalk between GAMs and glioma cells, contributing to our understanding of glioma progression within the tumor microenvironment.
Comparative effectiveness of Korean medicine treatment for idiopathic central precocious puberty: A Bayesian network meta-analysis
Authors: Shim Soo-Bo , Lee Hyun-Hee , Choi Eun-Young , Son Mi-Ju , Lee Hye-Lim
Published: December 2024

Background:

The purpose of this study is to analyze the comparative effect of the Korean medicine treatment for idiopathic central precocious puberty (ICPP) using Bayesian network meta-analysis (NMA).

Methods:

Seventeen electronic databases were used to search for randomized controlled trials (RCTs) that evaluated various Korean medicine treatments for ICPP. R software (version 4.2.3) was used to perform NMA. The risk of bias was assessed using the Risk of Bias 2 tool proposed by the Cochrane Collaboration. The results of NMA were expressed as network map, SUCRA, and Rank plot.

Results:

A total of 81 RCTs were included in the NMA. The gonadotropin-releasing hormone agonist (GnRHa) was the most effective for growth rate, followed by herbal medicine (HM) combined with GnRHa. The combination of HM and auricular plaster therapy was the most effective in improving the bone age index and ovarian volume, and megestrol was the most effective in improving uterine volume. The combination of HM, auricular plaster therapy and GnRHa was the most effective in improving follicle-stimulating hormone, and the combination of HM and GnRHa was the most effective in improving luteinizing hormone and estradiol.

Conclusion:

The combination of HM and GnRHa generally showed greater effectiveness compared to GnRHa monotherapy or HM monotherapy. Although there have been few reports of adverse events related to HM, additional research and practical experience are needed. Further diverse studies should be conducted to support the decision-making process of patients and clinicians during the diagnosis and treatment of ICPP.
Analysis of lung microbiota in pediatric pneumonia patients using BALF metagenomic next-generation sequencing: A retrospective observational study
Authors: Lu Sukun , Sun Ling , Cao Lijie , Zhao Mengchuan , Guo Yuxin , Li Mei , Duan Suxia , Zhai Yu , Zhang Xiaoqing , Wang Yakun , Gai Wei , Cui Xiaowei
Published: December 2024

The contribution of the lung microbiota to pneumonia in children of varying severity remains poorly understood. This study utilized metagenomic next-generation sequencing (mNGS) technology to elucidate the characteristics of lung microbiota and their association with disease severity. This retrospective study analyzed bronchoalveolar lavage fluid (BALF) mNGS data of 92 children diagnosed with pneumonia between January 2021 and July 2022. A comparative analysis of the lung microbiota was conducted between the severe pneumonia (SP) (n = 44) and non-severe pneumonia (NSP) (n = 48) groups. Compared to conventional microbiological tests (CMT), mNGS had a higher positivity rate in etiology detection (68% vs 100%). In the NSP group, the predominant type of infection was Mycoplasma pneumoniae single infection, whereas in the SP group, the main type involved a combination of M pneumoniae and bacterial infection. The top 3 identified microbial taxa in both the groups were M pneumoniae, Rothia mucilaginosa, and Schaalia odontolyticus. Although there were no significant differences in the α and β diversity of the lung microbiota between the SP and NSP groups, the abundance of M pneumoniae was higher in the SP group (P = .053). Spearman analysis indicated a highly significant positive correlation between the abundance of Prevotella melaninogenica and M pneumoniae (P < .001). Our analysis identified an association between M pneumoniae infections and disease severity. This study provides a foundation for a better understanding of the pathogenesis of pediatric pneumonia and the relationship between microorganisms.
Genetic prediction of serum micronutrient levels and the risk of frailty: Evidence from a Mendelian randomization study
Authors: Wen Bo , Wei Shizhuang , Huang Daolai , Zhang Chao , Liu Sisi , Wu Xianghua
Published: December 2024

Although observational studies have revealed a link between frailty and serum micronutrient levels, it remains unclear whether these 2 states are directly connected. Thus, Mendelian randomization (MR) was used to investigate the causal relationship between frailty and blood micronutrient levels. Summary-level data for 15 blood micronutrients (copper, selenium, zinc, calcium, iron, magnesium, potassium, folate, carotene, vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, and vitamin E) were obtained from people of European ancestry from the Integrative Epidemiology Unit. Single nucleotide polymorphisms associated with the frailty index were extracted from a published meta-analysis study in the UK Biobank and Swedish TwinGene. We used the inverse variance weighted (IVW) method for the primary analysis. We employed pleiotropy residual sum and outlier (MR-PRESSO) tests, MR-Egger intercepts, Cochran Q tests, and leave-one-out analysis to assess causality validity and robustness. Reverse MR analysis was used to determine reverse causation. The IVW results revealed that vitamin D (odds ratio [OR] = 1.096; 95% confidence interval [CI]: 1.019–1.178; P = .014) increased the likelihood of a high risk of frailty, whereas the frailty index had a protective effect on selenium (OR = 0.622; 95% CI: 0.396–0.977; P = .039), carotene (OR = 0.916; 95% CI: 0.858–0.979; P = .009), vitamin C (OR = 0.895; 95% CI: 0.837–0.957; P = .001), iron (OR = 0.921; 95% CI: 0.859–0.988; P = .022), and vitamin E (OR = 0.907; 95% CI: 0.847–0.971; P = .005). The reverse IVW analysis revealed no significant correlation between micronutrient levels and frailty indices. The study revealed causal links between vitamin D and the risk of frailty. Notably, our findings highlight the necessity of adjuvant vitamin D in frailty management.
Nonstenotic carotid artery plaques on computed tomography angiography in embolic stroke of undetermined source
Authors: Demir Mustafa , Semiz-Oysu Aslihan , Ozsezen Eda , Yasar Yunus
Published: December 2024

This study aims to evaluate the role of <50% stenotic cervical carotid artery plaques in embolic stroke of undetermined source (ESUS), focusing on plaque characteristics in symptomatic versus asymptomatic carotid arteries (contralateral). In this cross-sectional observational study, 81 patients who met the diagnostic criteria for ESUS and underwent were retrospectively analyzed. Carotid plaques causing <50% stenosis were examined, noting features such as plaque thickness, degree of luminal stenosis, irregularity, ulceration, calcification, and hypodensity. These characteristics were compared between the ipsilateral and contralateral carotid arteries. The study involved 33 men and 48 women, with plaques ≥3mm thick significantly more common in the ipsilateral carotid arteries (P < .05). Notable features such as plaque ulceration, irregularity, noncalcified plaque, and hypodensity were significantly more frequent ipsilaterally (P < .05). Of the plaque patients, 54.3% (44/81) were on the ipsilateral side, compared to 29.6% (24/81) on the contralateral side (P = .0024). Our findings underscore the potential significance of non-stenotic carotid plaques in ESUS. These plaques, especially those with certain high-risk characteristics, are more prevalent ipsilaterally and should be considered in clinical evaluations and treatment of ESUS.
Assessment of a manual therapy and acupressure method as a treatment of nonspecific low back pain: A prospective, observational and non-interventional cohort study
Authors: Ducret Gilles , Guillaume Marc , Fardini Yann , Vejux Sandrine , Chaabi Hassène
Published: December 2024

The first-line treatment for nonspecific low back pain (LBP) relief is physical exercise; however, there is no uniformity in recommendations regarding the type of exercise, and physicians predominantly prescribe pharmacological treatments. This creates a treatment gap in non-pharmacological management of LBP. Preliminary data suggest that manual therapy and acupressure could be relevant therapeutic options. The primary objective of this study was to describe the evolution of pain in patients with nonspecific LBP persisting for at least 4 weeks who received 2 treatment sessions combining manual therapy with acupressure (Biokinergie® method) as part of their routine management. In this prospective, observational, and non-interventional study, participants were monitored on the days of manual therapy session delivery (initial visit on Day 0 and follow-up visit on Day 21). Follow-up assessments occurred 3 days and 3 weeks post-therapy sessions. A total of 114 participants suffering from LBP for a median duration of 11.9 weeks were enrolled from May 2021 to May 2023. The intensity of average pain experienced over a 24-hour period was significantly reduced on Day 24 (−36.0 ± 27.2 mm on a visual analog scale of 100 mm, P < .001), with 82 (75.2%) participants reporting a decrease of at least 20 mm. Participants reported significant reductions in pain (−25.9 ± 23.9 mm on Day 3, −29.7 ± 26.7 mm on Day 21, and −40.9 ± 28.3 mm on Day 42, P < .001) and functional disability (Roland-Morris Disability Questionnaire score: −5.4 ± 0.4 points on Day 21 and −7.4 ± 0.4 points on Day 42, P < .001). This was associated with an improved Dallas Pain Questionnaire score, indicating a reduced impact of LBP on daily activities (−27.2 ± 2.0% on Day 21 and −35.8 ± 2.0% on Day 42, P < .001). Posttreatment, most participants (86.3%) reported reduced analgesic intake compared to baseline, and 83.3% were very satisfied with the therapy. A significant and clinically relevant reduction in lumbar pain was observed after 2 sessions of manual therapy combined with acupressure, paving the way for future clinical research.
Pathological roles of mitochondrial dysfunction in endothelial cells during the cerebral no-reflow phenomenon: A review
Authors: Luo Xia , Zhang Shaotao , Wang Longbing , Li Jinglun
Published: December 2024

Emergency intravascular interventional therapy is the most effective approach to rapidly restore blood flow and manage occlusion of major blood vessels during the initial phase of acute ischemic stroke. Nevertheless, several patients continue to experience ineffective reperfusion or cerebral no-reflow phenomenon, that is, hypoperfusion of cerebral blood supply after treatment. This is primarily attributed to downstream microcirculation disturbance. As integral components of the cerebral microvascular structure, endothelial cells (ECs) attach importance to regulating microcirculatory blood flow. Unlike neurons and microglia, ECs harbor a relatively low abundance of mitochondria, acting as key sensors of environmental and cellular stress in regulating the viability, structural integrity, and function of ECs rather than generating energy. Mitochondria dysfunction including increased mitochondrial reactive oxygen species levels and disturbed mitochondrial dynamics causes endothelial injury, further causing microcirculation disturbance involved in the cerebral no-reflow phenomenon. Therefore, this review aims to discuss the role of mitochondrial changes in regulating the role of ECs and cerebral microcirculation blood flow during I/R injury. The outcomes of the review will provide promising potential therapeutic targets for future prevention and effective improvement of the cerebral no-reflow phenomenon.
Advancements in the application of precision nursing model on hemodialysis for diabetic nephropathy: A review
Authors: Ma Jing , Ma Dan-Wei
Published: December 2024

This study explores the application and advancements of precision nursing model (PNM) in hemodialysis for diabetic nephropathy patients. Diabetic nephropathy is a severe complication of diabetes, frequently leading to end-stage renal disease and necessitating long-term hemodialysis. The PNM aims to enhance treatment outcomes and patient quality of life through individualized care plans, multidisciplinary collaboration, and continuous quality improvement. Research indicates that this model significantly improves clinical indicators and patient satisfaction, demonstrating broad applicability. This paper provides a detailed overview of the definition, theoretical foundation, implementation strategies, and specific interventions of the PNM, and evaluates its effectiveness in hemodialysis. Additionally, it addresses the challenges faced in implementation and suggests future research directions. Emphasis is placed on the need for long-term studies, technological innovations, and cost-effectiveness analyses to further integrate precision nursing into clinical practice.
Impact of occupational stress and musculoskeletal disorders on job satisfaction among Chinese dental hygienists: An observational study
Authors: Wei Jingyi , Zhong Feiyang , Cao Zheng , Huang Cheng-Yi
Published: December 2024

Dental hygienists in China face unique occupational challenges, with their job satisfaction being pivotal to performance. This study investigates the interplay between job satisfaction and occupational stress, burnout, and musculoskeletal disorders (MSDs) among this group. A cross-sectional survey was conducted involving 21 female dental hygienists from Sir Run Run Shaw Hospital. Data were collected on general information, occupational stress (using the Perceived Stress Scale), burnout (Maslach Burnout Inventory), MSDs, and job satisfaction. High levels of occupational stress and burnout were reported, yet these did not significantly correlate with job satisfaction (P > .05). In contrast, MSDs showed a significant negative correlation with job satisfaction (P = .004). Factors significantly associated with job satisfaction included effective collaboration, quality of work, institutional support, patient care, and work flexibility. While stress and burnout are prevalent among Chinese dental hygienists, they do not directly impact job satisfaction. MSDs, however, significantly affect satisfaction levels. The study suggests that addressing MSDs and enhancing workplace factors can improve job satisfaction and retention in the profession.
Optimal wearable camera mount locations for medical supervision during simulated out-of-hospital cardiopulmonary resuscitation
Authors: Jeong Joo , Song Kyoung-Jun , Lee Jung Chan , Shin Sang Do , Kim Yu Jin
Published: December 2024

The quality of the visual information transmitted from a scene is crucial for effective medical supervision in prehospital settings. This study investigated the influence of wearable camera mount locations on visibility during simulated out-of-hospital cardiopulmonary resuscitation. A prospective, observational, non-randomized simulation study was conducted to replicate a cardiac arrest scenario adhering to an advanced life support (ALS) protocol. Seven advanced emergency medical technicians (AEMTs) participated, and 5 camera mount locations were tested: the sternum, forehead, lateral side of the eyelid, mid-nasal, and glabella. Video recordings were captured from the Airway, Intravenous (IV), and Leading providers. Five experienced medical directors independently evaluated visibility scores (1–5) for each procedure with optimal visibility defined as a score of 4 to 5. Glabella mount demonstrated the highest median visibility score and interquartile range (5 [4–5]) and proportion of optimal visibility (77.5%) for most procedures across provider positions. Mixed models revealed significant estimates for the lateral side of the eyelid, mid-nasal, and glabella mounts compared to the sternum, with glabella having the largest effect size (estimate = 1.62). Generalized linear mixed models showed that the glabella mount had the highest odds ratio (OR = 8.07, 95% confidence interval [CI]: 3.01–21.6) to achieve optimal visibility. Wearable camera mount location significantly affected visibility during simulated resuscitation. Mounting cameras closer to eye level provided the most accurate visual data. Further research using objective measures, such as artificial intelligence, and evaluating the visibility of wearable cameras in real-world situations is warranted to optimize simulation-based training for prehospital care.
AMPK down-regulating Beclin-1 in prostate cancer patients with bone metastasis: An observational study
Authors: Chen Jiaxing , Hu Lingyun , Zhou Wangguang , Wang Chaoyang , Zhou Xuewu
Published: December 2024

Bone metastasis is frequently seen in patients, particularly those with prostate cancer, showing a higher hazard that deteriorates the quality of life of patients, leading to poor prognosis, which eventually causes significant mortality in prostate cancer patients. The present study investigated the mechanism of prostate cancer with bone metastasis by utilizing prostate specimens from patients. A total of 418 patients were initially enrolled for clinical analysis, including age, prostate-specific antigen (PSA) levels, body mass index (BMI), prostate magnetic resonance imaging (MRI), and bone MRI, while pathological analysis included grade group and carcinoma of the prostate. Patients were divided into a prostate cancer with bone metastasis group (group 1, prostate cancer patients) and benign prostate patient group (group 2, control group) and underwent subsequent immunohistochemical (IHC) detection. Expression of AMPK/Beclin-1 signaling pathways was analyzed through immunohistochemistry. Finally, 46 patients with prostate cancer bone metastasis (prostate cancer patients) and 61 patients with benign prostate (control group) met the inclusion criteria. We examined the expression levels of Beclin-1 and AMPK in human prostate tissues by IHC and found that Beclin-1 levels were negatively correlated with AMPK in prostate cancer with bone metastasis (P < .05). The results of this study suggest that AMPK-Beclin-1 significantly reduces prostate cancer metastasis to the bone in human tissues.
Long-term outcomes of Gamma Knife radiosurgery for trigeminal neuralgia patients with or without concomitant continuous pain
Authors: Dong Guijiang , Li Quanqing , Sun Jin , Chen E. , Lin Xiaoning , Tong Junjiang , Chen Hongjin , Yao Xiang , Wang Hongbo , Tian Xinhua
Published: December 2024

The effectiveness of Gamma Knife radiosurgery (GKRS) in treating trigeminal neuralgia (TN) has been demonstrated by a number of previous studies. However, there is a lack of research specifically documenting the initial and long-term outcomes of paroxysmal and persistent pain respectively following GKRS for TN with concomitant continuous pain (CCP). This study retrospectively analyzed pain outcomes and complications in 46 TN patients with CCP and 112 patients without CCP who underwent GKRS as initial surgical intervention at our institution from January 2019 to January 2024. Pain outcomes were classified as excellent (BNI I), good (BNI II–IIIa), and poor (BNI IIIb–V). Demographic and clinical data, pain outcomes, and complications were compared between patients with and without CCP. Subsequently, risk factors for poor outcomes after GKRS were evaluated using univariate and multivariate Cox regression analysis. The initial rate of poor outcomes in TN patients with CCP was similar to that of patients without CCP (15.8% vs 14.4%, P = .878). Following a minimum 6-month follow-up, the rate of poor pain outcomes increased to 37.0% in patients with CCP, compared to 38.4% in those without CCP (P = .968). Notably, the rate of long-term complete pain relief in patients without CCP was significantly higher than in those with CCP (35.7% vs 15.2%, P < .001). Poor response to medication (P < .001) was identified as an independent risk factors for poor outcomes after GKRS. While most TN patients with or without CCP can achieve favorable pain outcomes after GKRS, individuals with CCP were less likely to achieve complete pain relief compared to those without CCP.
Association between time to antibiotic and mortality in patients with suspected sepsis in the Emergency Department: post hoc analysis of the 1-BED randomized clinical trial
Authors: Philippon Anne-Laure , Lebal Soufiane , Cancella de Abreu Marta , Gerlier Camille , Mirò Oscar , Simon Tabassome , Freund Yonathan
Published: December 2024

Importance

The impact of early antibiotics on mortality in patients with suspected sepsis in the emergency department (ED) remains debated, particularly in patients with less severe presentations or before infection confirmation.

Objective

To evaluate the association between time to antibiotic administration and 28-day in-hospital mortality among patients with suspected sepsis in the ED.

Design, setting, and participants

Post hoc analysis of the 1-bundle emergency department trial, a multicenter, stepped-wedge cluster-randomized controlled trial conducted in 23 EDs in France and Spain. A total of 872 patients with suspected sepsis were included between June 2022 and September 2023. All patients with available data on antibiotic administration were analyzed, and a subgroup of patients with no hypotension was also assessed.

Exposures

Time to antibiotic administration. The effect of time to fluid resuscitation was also assessed.

Main outcomes and measures

The primary outcome was in-hospital mortality at 28 days. Secondary outcomes included all-cause 28-day mortality, ICU length of stay, number of days without vasopressors at day 28, and change in Sequential Organ Failure Assessment score at 72 h.

Results

Among 872 patients (mean age 66 years; 41% female), 859 had available data on antibiotic administration (primary analysis) and 791 (92%) received antibiotics. The median time to antibiotic administration was 61 min (IQR 14–169), with 457 patients (58%) receiving antibiotics within 1 h. In-hospital mortality at 28 days was 14.7% for patients who did not received antibiotic within 1 h versus 9.6% for patients who did [adjusted odds ratio (aOR) 2.00 (1.24–3.23)]. There was an aOR of 1.06 (1.02–1.1) for each hour of delay for antibiotic administration. This effect was confirmed in patients without hypotension [aOR 2.02 (1.08–3.76) for patients who received antibiotics beyond 1 h]. Time to fluid resuscitation was not associated with 28-day in-hospital mortality.

Conclusion and relevance

In patients with suspected sepsis presenting to the ED antibiotic administration beyond 1 h was associated with a two-fold increased 28-day in-hospital mortality. This effect persisted in patients without hypotension.
Does a Prolonged Sham Theta Burst Stimulation Intervention Regimen Outperform Standard Care in Terms of Functional Recovery and Pain Relief After an Upper Limb Fracture?
Authors: Proulx-Bégin Léa , Jodoin Marianne , Brazeau Daphnée , Herrero Babiloni Alberto , Provost Catherine , Rouleau Dominique M. , Arbour Caroline , De Beaumont Louis
Published: December 2024

Objective

In a recent sham-controlled 13-session prolonged continuous theta burst stimulation intervention protocol, recovery from upper limb fracture at both 1 and 3 months was better than anticipated in patients assigned to the sham intervention group. To determine whether potential placebo effect and close patient monitoring affected recovery, the current study aimed to compare clinical outcomes between sham-treated participants who also received standard care with similarly injured patients who only received standard care.

Methods

Twenty participants with isolated upper limb fractures from the sham group were seen 13 times post-fracture (1 baseline session, 10 treatments, and 2 follow-ups [1 and 3 months]) over 3 months. They completed the self-reported Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire and the Numerical Rating Scale for pain assessment at 1 and 3 months post-fracture. Two control groups were recruited: 43 participants at 1 month post-fracture and another 40 participants at 3 months post-fracture. These control groups completed the same questionnaires online, without any lab visits.

Results

At 1 month, patients from the sham group reported significantly less functional impairments on the DASH (p = .010). At 3 months, significantly more patients from the control group reported functional limitations (72.5% versus sham’s 40%, p = .015).

Conclusions

Although preliminary, these findings suggest clinically significant beneficial effects of the sham intervention over the standard care groups. This positive sham intervention effect may be attributed to a placebo response that includes the placebo effect associated with sham rTMS, but also the impact of various factors such as the close monitoring of the injury.
Longitudinal Changes in Tenofovir and Tenofovir Diphosphate Concentrations Among Pregnant Women Using Oral PrEP for HIV Prevention: Findings From Durban, South Africa
Authors: Beesham Ivana , Jaggernath Manjeetha , Kriel Yolandie , Hao Jiaying , Smith Patricia M. , Haberer Jessica E. , Hendrix Craig W. , Psaros Christina , Bangsberg David R. , Smit Jennifer A. , Matthews Lynn T.
Published: December 2024

Background:

Pregnant women are vulnerable to HIV acquisition. Oral HIV pre-exposure prophylaxis (PrEP) is safe and effective for use during pregnancy. We describe PrEP adherence among pregnant women using multiple measures.

Methods:

We conducted a secondary data analysis among women enrolled in a study evaluating an adherence intervention for PrEP among those planning for and with pregnancy in South Africa. Our analysis included women who used PrEP and became pregnant. Longitudinal PrEP use was assessed using concentrations of tenofovir (TFV) in plasma, tenofovir diphosphate (TFV-DP) in dried blood spots, and electronic pillcap data from quarterly visits. Plasma TFV ≤10 ng/mL and TFV-DP ≤16.6 fmol/punch were below quantifiable limits. Data were analyzed during prepregnancy (quarter before pregnancy) and pregnancy trimesters.

Results:

Among 35 women, 69% were 18–24 years old, 40% were nulliparous, and 94% did not know their partner's HIV serostatus. Median pillcap adherence was 55%–80% and was highest during prepregnancy (72%, interquartile range: 54%–86%) and third trimester (80%, interquartile range: 30%–94%). The proportion of women with quantifiable TFV was 47% (n = 8/17) prepregnancy and 33% (n = 9/27), 19% (n = 4/21), and 14% (n = 2/14) for trimesters 1–3, respectively. TFV-DP was detected in 75% of samples (n = 12/16) prepregnancy, and 50% (n = 13/26), 29% (n = 6/21), and 27% (n = 4/15) for trimesters 1–3, respectively. No women acquired HIV during pregnancy.

Conclusions:

PrEP use declined during pregnancy by all measures. Discrepancies between pillcap measurements and drug concentrations could be due to physiologic changes during pregnancy or under- or overuse of the pillcaps. Determining what drug metabolite concentrations are needed to confer protection during pregnancy is important for optimizing counseling and prevention support.
Model-Based Prioritization of Adolescent Girls and Young Women for HIV Prevention Services Based on Data From 13 Sub-Saharan African Countries
Authors: Gutreuter Steve , Denhard Langan , Logan Joseph E. , Blanton Jesse , Cham Haddi Jatou
Published: December 2024

Background:

Adolescent girls and young women (AGYW) aged 15–24 years are more likely to acquire HIV than their male counterparts, and well-targeted prevention interventions are needed. We developed a method to quantify the risk of HIV acquisition based on individual risk factors and population viral load (PVL) to improve targeting of prevention interventions.

Setting:

This study is based on household health survey data collected in 13 sub-Saharan African countries, 2015–2019.

Methods:

We developed a Bayesian spatial model which jointly estimates district-level PVL and the probability of infection among individual AGYW, aged 15–24 years, based on individual behavioral/demographic risk factors and area-level PVL. The districts (second subnational level) typically comprise the areas of estimation. The model borrows strength across countries by incorporating random effects, which quantify country-level differences in HIV prevalence among AGYW.

Results:

The combined survey data provided 52,171 questionnaire responses and blood tests from AGYW, and 280,323 blood samples from all respondents from which PVL was estimated. PVL was—by far—the most important predictor of test positivity [adjusted odds ratio (aOR) = 70.6; 0.95-probability credible interval 20.7–240.5]. Having a partner with HIV increased the odds of testing positive among AGYW who were never (aOR = 12.1; 7.5–19.6) and ever pregnant (aOR = 32.1; 23.7–43.4). The area under the cross-validated receiver-operating characteristic curve for classification of test positivity was 82%.

Conclusion:

The fitted model provides a statistically principled basis for priority enrollment in HIV prevention interventions of those AGYW most at risk of HIV infection and geographic placement of prevention services.
LncRNA-H19 is downregulated in ectopic endometrial stromal cell by multiple medicines in vitro
Authors: Gao Han , Gao Xiao-Xiao , Shao Wei , Wang Jia-Qi , Liu Song-Ping
Published: December 2024

Objective:

According to our previous studies, it has been found that long noncoding RNA-H19 (lncRNA H19)-ITGB3-miR-124-3p axis can regulate cell proliferation and invasion of the ectopic endometrium, which could be the potential pathway for treating endometriosis by a key medicine. The aim of this study was to investigate the roles of metformin, aspirin, artemisinin, and berberine in regulating the expression of lncRNA-H19 in ectopic endometrial stromal cells (ecESCs) and explore novel medicines for the treatment of endometriosis.

Methods:

Isolation of ESCs from the ectopic endometrium of patients with endometriosis and treatment with metformin at 0.1 mmol/L, aspirin at 5.00 mmol/L, artemisinin at 20 μmol/L, and berberine at 20 μmol/L for 0, 12, 24, and 48 h. LncRNA-H19 levels in ecESCs after treatment were evaluated using real-time polymerase chain reaction, and changes in cell proliferation and invasion were determined using Cell Counting Kit-8 and Transwell assays.

Results:

lncRNA H19 levels in ecESCs in the metformin, aspirin, artemisinin, and berberine groups were significantly lower than those in the control group, with inhibition of cell proliferation and invasion; metformin and berberine showed the highest efficiency.

Conclusions:

Metformin and berberine inhibited ecESC proliferation and invasion by downregulating lncRNA-H19 levels, offering a novel treatment for endometriosis.
Mendelian randomization evidence for lung function mediates the association between childhood allergies (age <16 years) and essential hypertension
Authors: Long Yu-Hang , She Jun-Sen , Guo Fei , Zhou Bo-Kang , Fang Chen , Hu Yi-Zhi , Gao Ling , Huang He-Feng
Published: December 2024

Objective:

This study aimed to investigate the influence of lung function on the relationship between allergies and hypertension, thereby elucidating significant potential mechanisms from a genetic standpoint. We investigated the causal relationship between childhood allergies (age <16 years) and essential hypertension and identified and quantified the role of lung function (forced vital capacity [FVC] and forced expiratory volume in the first second/forced vital capacity [FEV1/FVC]) as potential mediators.

Methods:

Using data from a genome-wide association study and the Fenn Genn consortium, a two-sample Mendelian randomization (MR) analysis of genetically predicted childhood allergies (7128 cases and 211,703 controls) and essential hypertension (116,714 cases and 1,032,659 controls) was performed. Furthermore, we used two-step MR to quantify the effect of lung function-mediated childhood allergies on essential hypertension. The FVC and FEV1/FV sample size was 371, 898.

Results:

Childhood allergies were associated with increased odds of developing essential hypertension (odds ratio [OR] = 1.0900, 95% confidence interval [CI] = 1.0034–1.1842, P = 0.0414). No strong evidence that genetically predicted essential hypertension affected childhood allergy risk was identified (OR = 1.0631, 95% CI = 0.9829–1.1498, P = 0.1264). The proportion of genetically predicted childhood allergies mediated only by FVC was 5.67% (95% CI, 5.13%–5.73%).

Conclusion:

A causal relationship between childhood allergies and essential hypertension was identified, with a proportion of the effect mediated by FVC. Therefore, implementing early interventions in children with allergies is imperative to mitigate the long-term risk of developing hypertension. Further research is required to identify additional risk factors as potential mediators.
Predictors of healthy days at home: Benchmarking long-term outcomes in geriatric trauma
Authors: Castillo-Angeles Manuel , Zogg Cheryl K. , Smith Charlotte B. , Etheridge James C. , Wu Christine , Jarman Molly P. , Nitzschke Stephanie , Askari Reza , Cooper Zara , Salim Ali , Havens Joaquim M.
Published: December 2024

BACKGROUND

Quality benchmarking has recently evolved from a historical focus on short-term morbidity and mortality as the key metrics to assessing long-term outcomes. Long-term quality metrics have been shown to provide a more complete assessment of geriatric trauma care. Among these metrics, patients' average number of healthy days at home (HDAH) proports to be a useful administrative claims-based marker of patient functional status. Our goal was to determine the predictors of HDAH among injured older adults.

METHODS

Medicare inpatient claims (2014–2015) were used to identify all geriatric trauma patients. Patients' number of HDAH was measured from the date of discharge and calculated as the total sum of patients' time during that period less any time spent in the hospital or emergency department, step-down/rehabilitation/nursing care, home health, or after death within a 365-period after index admission. Controlling for demographic, injury severity, and hospital-level characteristics, multivariable regression analyses were performed to identify the factors associated with increased HDAH.

RESULTS

We included 772,109 geriatric trauma patients. The mean age was 82.15 years (SD, 8.49 years), 68.3% were female, and 91.6% were White. The median HDAH was 351 days (interquartile range, 351–355 days). After adjusted analysis, age, Black race, Charlson Comorbidity Index (CCI), and care at a level 3/nontrauma center were associated with fewer HDAH within 365 days after discharge.

CONCLUSION

This study suggests that higher level trauma centers provide more HDAH after index admission for injured older adults. Future studies should focus on correlating HDAH with more granular but less readily accessible quality of life metrics.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; III.
Experimental Design Optimization for Brain Microstructure Imaging via Automatic Differentiation
Authors: Farooq Hamza , Chen Yongxin , Rasool Ghulam , Georgiou Tryphon T. , Lenglet Christophe
Published: December 2024

Accurate characterization of the brain microstructure using diffusion MRI (dMRI) relies on optimal (i.e. information-rich) scanning protocols. Presently, without such protocols, extensive datasets are necessary to image the intricate microarchitecture of the brain by fitting complex biophysical models to the data. This impedes the full realization of dMRI’s potential, particularly in time-constrained clinical scans. To tackle this, we introduce a novel framework based on the Cramér-Rao lower bound (CRLB) to optimize dMRI protocols for any multi-compartment biophysical models, to accurately capture features like axonal diameter index and multiple fiber orientations in a voxel. Unlike previous methods, limited in model complexity or parameter scope, our framework handles all model parameters, including water diffusivities, enhancing estimation fidelity. Leveraging automatic differentiation and parallel computing via TensorFlow, this approach systematically explores the entire parameter space for comprehensive scanning protocol optimization. By optimizing dMRI protocols, this work stands to significantly enhance biophysical modeling accuracy, thereby deepening our understanding of the brain microstructure in health and disease.
Caloric restriction: A potential approach for mitigating neuronal damage: Lesson from cellular model of Alzheimer disease
Authors: Sharma Apoorv , Bhardwaj Monika , Kumar Vijay , Islam Asimul , Prakash Hridayesh
Published: December 2024

Alzheimer’s disease is a neurodegenerative disorder and characterized by amyloid beta accumulation, synaptic dysfunction, and oxidative stress, lacks effective therapies. Caloric restriction mimetics such as fisetin and chlorogenic acid, natural polyphenols with antioxidant and autophagy-inducing properties, show promise in mitigating age-related diseases. This study investigates their neuroprotective effects against amyloid beta induced toxicity in differentiated human neuroblastoma SHSY5Y cells. Amyloid beta exposure disrupted redox homeostasis, impaired autophagy, induced mitochondrial dysfunction, and exacerbating neuronal degeneration. Fisetin and chlorogenic acid treatments reversed these deleterious effects by restoring redox balance, suppressing reactive oxygen species and upregulating critical antioxidant enzymes like SOD1, GSR, and catalase. These compounds also attenuated amyloid beta induced mitophagy via reduced PINK1 expression and restored mitochondrial fusion by upregulating Mfn2. Autophagy-related pathways were significantly modulated, evidenced by increased AMPK and decreased mTOR mRNA levels, alongside elevated expression of ATG101, ATG13, ULK1, P62 and reduced ATG5 levels. Docking studies also revealed binding of fisetin and CGA within the binding pockets of AMPK and FKBP12 supporting their interaction. Furthermore, fisetin and CGA improved synaptic integrity by upregulating PSD95 and synaptophysin and reducing acetylcholinesterase expression. These findings highlight their potential in ameliorating amyloid beta induced neuronal toxicity through autophagy activation, synaptic preservation, and mitochondrial function enhancement. While this study demonstrates the transcriptional impact and binding affinities of these caloric restriction mimetics further translational and biophysical analyses are required to elucidate their mechanisms and confirm their therapeutic viability. This research underscores the potential of fisetin and CGA as neuroprotective agents, offering promising therapeutic avenues for combating related Alzheimer’s disease neuropathies.

Abstract Figure
Enhanced Subjective Performance Achievement in Wind Instrument Playing through Positive Memory Recall: Effects of Sympathetic Activation and Emotional Valence
Authors: Watanabe Aiko , Kondoh Sotaro , Samma Tomohiro , Fujii Shinya
Published: December 2024

Controlling physiological and psychological states before a performance is essential for professional musicians to realize their full potential. However, the characteristics of the optimal pre-performance state remain unclear. While an increase in sympathetic nervous system activity is typically observed before performance, when associated with anxiety, it can degrade the performance quality. This study examined whether recalling positive autobiographical performance memories enhances subjective performance achievement, accompanied by increased emotional arousal, valence, and autonomic nervous system activity. Thirty-six professional wind instrument players participated in the study. Prior to performing musical pieces, participants engaged in one of three conditions: (1) recalling positive autobiographical memories, (2) recalling negative autobiographical memories, or (3) imagining routine pre-performance activities (no-memory condition). During the memory recall phase, heart rate was measured. After each performance, participants rated their subjective arousal, valence, and performance achievement. We calculated the heart rate variability indices, specifically SD1 (reflecting parasympathetic nervous system activity) and SD2/SD1 (reflecting sympathetic nervous system activity). The results showed that performance achievement, arousal, and valence were significantly higher in the positive than in the negative condition. Our path analysis further revealed that an increase in SD2/SD1 did not directly predict performance achievement; instead, it was associated with an increase in emotional valence, which in turn led to improved performance. These findings suggest that recalling positive performance memories activates sympathetic nervous system activity and fosters positive emotions, thereby enhancing the performance achievement of professional musicians.