bluuebunny/crossref_metadata_2025 huggingface dataset:
Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring
Authors: Mussai Ei‐Xia , Lofft Zoe A. , Vanderkruk Ben , Boonpattrawong Nicha , Miller Joshua W. , Smith Andre , Bottiglieri Teodoro , Devlin Angela M.
Published: September 2023

Epidemiological studies have reported discrepant findings on the relationship between folic acid intake during pregnancy and risk for gestational diabetes mellitus (GDM). To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5× recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of diet‐induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation are not due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (western and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex‐specific hepatic gene expression profiles were observed in the fetal offspring from supplemented dams but this differed between western and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype and has sex‐specific effects on offspring pancreas and liver.
GPER Acts Through the cAMP/Epac/JNK/AP-1 Pathway to Induce Transcription of Alpha 2C Adrenoceptor in Human Microvascular Smooth Muscle Cells
Authors: Fardoun Manal , Nasser Suzanne A. , El-Yazbi Ahmed F. , Eid Ali H.
Published: September 2023

Raynaud's phenomenon, which results from exaggerated cold-induced vasoconstriction, is more prevalent in females than males. We previously showed that estrogen increases the expression of alpha 2C-adrenoceptors (α2C-AR), the sole mediator of cold-induced vasoconstriction. This effect of estrogen is reproduced by the cell-impermeable form of the hormone (E2:bovine serum albumin [BSA]), suggesting a role of the membrane estrogen receptor, G-protein-coupled estrogen receptor [GPER], in E2-induced α2C-AR expression. We also previously reported that E2 upregulates α2C-AR in microvascular smooth muscle cells (VSMCs) via the cAMP/Epac/Rap/JNK/AP-1 pathway, and that E2:BSA elevates cAMP levels. We, therefore, hypothesized that E2 uses GPER to upregulate α2C-AR through the cAMP/Epac/JNK/AP-1 pathway. Our results show that G15, a selective GPER antagonist, attenuates the E2-induced increase in α2C-AR transcription. G-1, a selective GPER agonist, induced α2C-AR transcription, which was concomitant with elevated cAMP levels and JNK activation. Pretreatment with ESI09, an Epac inhibitor, abolished G-1-induced α2C-AR upregulation and JNK activation. Moreover, pretreatment with SP600125, a JNK-specific inhibitor, but not H89, a PKA-specific inhibitor, abolished G-1-induced α2C-AR upregulation. In addition, transient transfection of an Epac dominant negative mutant (Epac-DN) attenuated G-1-induced activation of the α2C-AR promoter. This inhibitory effect of Epac-DN on the α2C-AR promoter was overridden by the cotransfection of constitutively active JNK mutant. Furthermore, mutation of AP-1 site in the α2C-AR promoter abrogated G1-induced expression. Collectively, these results indicate that GPER upregulates α2C-AR through the cAMP/EPAC/JNK/AP-1 pathway. These findings unravel GPER as a new mediator of cold-induced vasoconstriction, and present it as a potential target for treating Raynaud's phenomenon in estrogen-replete females.
Reverse Abdominoplasty in a Patient Presenting with Subcostal Nephrectomy Scar and Transverse Muscle Incisional Hernia
Authors: Alves André S. , Martineau Jérôme , Dupuis Arnaud , Zuo Katie , Kalbermatten Daniel F. , Oranges Carlo M.
Published: September 2023

Abdominoplasty and its different approaches have been widely described to improve abdominal wall contour. However, the role of reverse abdominoplasty, a less commonly performed technique, and its indications are not fully understood. Recent advances in the understanding of the vascular supply to the anterior abdominal wall have made this technique more popular, but there is still limited information available in the literature. In this report, we present the case of a 52-year-old woman who underwent a reverse abdominoplasty using an existing subcostal scar from a previous nephrectomy. No surgical complications were observed, and the patient achieved both aesthetic and functional improvement after 6 months of follow-up. Reverse abdominoplasty can be a reliable option for maintaining adequate blood supply and achieving a satisfactory cosmetic result in cases where there is a pre-existing subcostal scar.
3D Printing and Surgical Simulation for Management of Large and Giant Congenital Melanocytic Nevi
Authors: Solomon Santana S. , Sitzman Thomas J.
Published: September 2023

Tissue expansion with subsequent adjacent tissue transfer is often the preferred and sometimes the only option for reconstruction of large and giant congenital melanocytic nevi. Successful reconstruction with maximal efficiency and optimal aesthetic outcome requires careful planning of the tissue transfer, which itself requires careful selection of the tissue expander size and positioning. Unfortunately, there is little opportunity to gain experience in these skills due to the rarity of this condition. In situations where there is a rare condition that requires a complex technical procedure with much interoperative decision-making, surgical experience can be supplemented with the use of surgical simulation. In this article, we report on the use of three-dimensional patient imaging, three-dimensional printing, and surgical simulation for planning the reconstruction of large and giant congenital melanocytic nevi. We describe how this technology allows us to simulate multiple different approaches to expander placement and adjacent tissue transfer. We also describe how these simulations can be used to create cutting guides to guide final incision design and reduce intraoperative decision-making. Finally, we discuss how these models can be used to educate patients and families about the process and outcomes of nevus excision and reconstruction.
Retrospective Study of Preoperative Laser Peripheral Iridotomy Versus Intraoperative Surgical Peripheral Iridectomy in Descemet Membrane Endothelial Keratoplasty
Authors: Warren Nichelle , Sun Lucy , Behshad Soroosh , Kim Joung , Thulasi Praneetha
Published: September 2023

Purpose:

The aim of this study was to examine the outcomes of laser peripheral iridotomy (LPI) and surgical peripheral iridectomy (SPI) for Descemet membrane endothelial keratoplasty (DMEK) and DMEK with cataract extraction (triple DMEK).

Methods:

This retrospective interventional study included 135 eyes of 135 patients who underwent DMEK alone or triple DMEK. Primary outcomes were graft detachments necessitating rebubbling, repeat grafts, and pupillary block. The secondary outcomes included rejection, cystoid macular edema, uveitis, intraoperative hyphema, visual disturbances, and surgical time.

Results:

Thirty-one eyes in the LPI group and 104 eyes in the SPI group were included. Fifty-six eyes had DMEK alone, and 79 had triple DMEK. Visually significant graft detachments occurred in 7 of 31 eyes in the LPI group versus 19 of 104 eyes in the SPI group (P = 0.61). No statistical significance in DMEK alone versus triple DMEK groups (P = 0.61 vs. P > 0.99). Two patients in the LPI group and 5 in the SPI group required regraft (P = 0.66). One (3.2%) experienced pupillary block compared with 5 (4.8%) (P = 0.99) in the LPI and SPI groups, respectively. Secondary outcomes were similar in both groups ranging from 0% to 3% (P > 0.99). None had visual disturbances. In DMEK alone, duration of surgery was significantly shorter in the LPI versus SPI group (32.8 vs. 44.1 minutes, P = 0.02).

Conclusions:

This study demonstrated similar outcomes between LPI and SPI, although the LPI group had a shorter duration of surgery when DMEK was performed alone. The remainder of the outcomes demonstrated no statistically significant differences.
Open-labeled Randomized Controlled Trial on Efficacy of Azithromycin Versus Doxycycline in Pediatric Scrub Typhus
Authors: Sharma Anjali , Mahajan Vidushi , Guglani Vishal , Singla Nidhi , Saini Shiv Sajan
Published: September 2023

Background:

Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus.

Study design:

Open-label randomized controlled trial.

Methods:

Children 1–14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ.

Results:

We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83–1.08)]. On Kaplan–Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035).

Conclusion:

AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991.
Clozapine-Associated Agranulocytosis
Authors: Magistri Carlo , Mellini Cristiano
Published: September 2023

Background

Clozapine is a very effective therapeutic option for schizophrenic disorders that have been refractory to most other therapies. This extremely positive aspect clashes easily with an adverse effect of the drug that is deemed to be a very dangerous one: agranulocytosis. We asked whether the mandatory strict hematological follow-up prescribed in the black box warning of clozapine's label is proportioned to the actual incidence of agranulocytosis, considering that is the main reason that such a drug is often used only late in the treatment course.

Methods

We carried out a systematic review of reports examining clozapine administration and agranulocytosis incidence. We specifically selected those where mild and moderate neutropenia was not used as a trigger to stop administration of clozapine, to better estimate the sheer incidence of agranulocytosis when clozapine was continued even with mild hematological effect, where detected. We used PubMed, MEDLINE, EMBASE, Cochrane, and ScienceDirect databases to identify clinical studies conducted between January 1975 and April 2023.

Results

We included 14 studies, mostly retrospective ones, that examined the incidence of hematological adverse effects in patients using clozapine. A total of 2354 subjects were included. The mean age of the subjects was 33.5 years. The mean duration of observation of subjects who took clozapine was 800 days, with a mean daily dose of 319.5 mg per day. Of the 2354 subjects examined, we found that 11 of them experienced agranulocytosis (0.47%).

Conclusions

These results suggest the evidence of a lower incidence of agranulocytosis than previously estimated and are in line with more recent meta-analyses. We may therefore think that clinical practice may demand a revision of the approach that both psychiatrists and supervising organizations often take when talking about clozapine.
Evaluation of a Yellowish-Tan Plaque Surrounding a Preexisting Nevus
Authors: Luu Yen , Han Joseph , Admani Shehla
Published: September 2023

Rapid changes in size and color at the site of a preexisting nevus may be concerning to both patients and medical providers. Distinguishment of benign versus malignant changes may be difficult, especially when there is concern for malignancy and in cases of nonspecific clinical presentation. The current case illustrates a common cause of yellowish-tan papules and plaques. This case also highlights clinical methods to distinguish this condition from similarly appearing presentations, as recognition and appropriate treatment of this condition using noninvasive techniques may prevent further invasive workup.
Parental Perspectives on Impact of Parental Presence Restrictions in the Neonatal Intensive Care Unit During the COVID-19 pandemic
Authors: MacNeil Morgan , Campbell-Yeo Marsha , McCulloch Holly , Hughes Brianna , Dol Justine , Marriott Nicola , Smith Victoria , Alcock Lynsey
Published: September 2023

Purpose:

To describe parental experiences in the neonatal intensive care unit (NICU) during the COVID-19 restrictions. We explore what parents found most challenging, the impact these restrictions had on them and their infant, and how they coped.

Methods:

A cross-sectional online survey was completed by parents of infants who required care in a Canadian NICU during the early period of the COVID-19 pandemic. Data from 3 questions were coded using thematic analysis.

Results:

Participants (n = 161) were primarily mothers (93%), with an average length of stay of 32.1 days. Three themes were identified from responses: (1) emotional and physical closeness of the parents to their infant; (2) physical and psychosocial well-being of the infant and parent; and (3) how parents coped, and strategies for moving forward. Parents reported that parental restriction policies adversely impacted their perceived physical and emotional closeness with their infant and their infant's physical and psychosocial well-being. Parents reported that being able to be present with their infant, having their partner able to be present with them, and effective communication helped them cope.

Conclusion:

Despite the need for some restrictive policies to control the spread of the virus, the benefits and risks to the overall well-being of the parents and infants must be weighed.
Evaluation of Comfort Behavior Levels of Newborn by Artificial Intelligence Techniques
Authors: Yigit Deniz , Acikgoz Ayfer
Published: September 2023

Background:

One of the scales most frequently used in the evaluation of newborn comfort levels is the Neonatal Comfort Behavior Scale (NCBS). It is important therefore that an increased use of the NCBS is encouraged through a more practical method of assessment.

Objective:

This study was carried out for the purpose of designing a means of assessing neonatal comfort levels by employing the techniques of artificial intelligence (AI).

Methods:

The AI-based study was conducted with 362 newborns under treatment in the neonatal intensive care unit of a hospital. A data collection form, the NCBS, and a camera system were used as data collection tools. The data were analyzed with the SPSS Statistics 21.0 program. Descriptive statistics and Cohen κ test were employed in the analysis.

Results:

The 2 researchers named in the study first labeled the audiovisual recordings of the 362 newborns in the study. These labeled audiovisual recordings were used in training (80%) as well as testing (20%) the AI model. The AI model displayed a rate of success of 99.82%.

Conclusion:

It was ultimately seen that the AI model that had been developed was a successful tool that could be used to determine the comfort behavior levels of newborns in the neonatal intensive care unit.
A bibliometric analysis of efferocytosis in cardiovascular diseases from 2001 to 2022
Authors: Hu Luoxia , Lv Zhengtian , Gu Yangyang , Zheng Tiantian , Kong Youjin , Mao Wei
Published: September 2023

Introduction:

In recent years, efferocytosis in cardiovascular diseases has become an intense area of research. However, only a few bibliometric analyses have been conducted in this area. In this review, we used CiteSpace 5.7. R2 and VOSviewer 1.6.17 software to perform text mining and knowledge map analysis. This study summarizes the latest progress, development paths, frontier research hotspots, and future research trends in this field.

Materials and methods:

Studies on efferocytosis in cardiovascular diseases were downloaded from the Web of Science Core Collection.

Results:

In total, 327 studies published by 506 institutions across 42 countries and regions were identified. The number of studies on efferocytosis in cardiovascular diseases has increased over time. Arteriosclerosis Thrombosis and Vascular Biology published the highest number of articles and was the top co-cited journal. Tabas Ira. was the most prolific researcher and co-cited the most. The most productive countries were the United States and China. Columbia University, Harvard Medical School, and Brigham Women’s Hospital were the 3 most productive institutions in the field of research. Keyword Co-occurrence, Clusters, and Burst analyses showed that inflammation, atherosclerosis, macrophages, and phagocytosis appeared with the highest frequency in these studies.

Conclusion:

Multinational cooperation and multidisciplinary intersections are characteristic trends of development in the field, and the immune microenvironment, glycolysis, and lipid metabolism will be the focus of future research.
The effect of the earliest COVID-19 outbreak on survival in uninfected advanced NSCLC patients receiving chemotherapy in Jiangsu Province, China: A retrospective cohort study
Authors: Lu Heng , Wang Yue , Feng Guoqiang , Shen Chaoyan , Zhou Xingqin , Han Jie
Published: September 2023

Coronavirus disease 2019 (COVID-19) is still rampant and uncontrolled across the globe. China’s strict epidemic prevention measures have had an impact on the treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study is to explore the impact of the COVID-19 outbreak on the uninfected NSCLC patients. The chemotherapeutic efficacy and survival of 89 uninfected advanced NSCLC patients were retrospectively analyzed. The endpoints were overall survival (OS), progression-free survival (PFS), and response rate. Forty and forty-nine patients with advanced NSCLC received chemotherapy during the COVID-19 outbreak and nonoutbreak periods, respectively. Mean delay time was 12.8 months for COVID-19 outbreak stage versus 5.68 months for nonoutbreak stage (P = .003). There was no significant difference in the rates of chemotherapy delay and discontinuation between the 2 groups (P = .055 and .239). Significant difference was not detected in median OS (15.8 months) for COVID-19 outbreak stage versus 16.0 months for nonoutbreak stage (adjusted hazard ratio, 1.058; 95% confidence interval, 0.593–1.888; P = .849); Median PFS was 7.9 months for COVID-19 outbreak stage versus 10.3 months for nonoutbreak stage (adjusted hazard ratio, 0.878; 95% confidence interval 0.513–1.503; P = .634). There was also no statistical difference in the disease control rate between the 2 groups (P = .137). The earliest COVID-19 outbreak had no significant impact on the PFS and OS in uninfected advanced NSCLC patients receiving chemotherapy. However, the mean delay time of receiving chemotherapy was prolonged during the COVID-19 outbreak.
Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study
Authors: Yan Zhaoqi , Xu Yifeng , Li Keke , Liu Liangji
Published: September 2023

Background:

The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations.

Methods:

In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The “inverse variance weighting” method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method.

Results:

Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = −0.20, 95% confidence interval [CI] = −0.25 to −0.15) and bioavailable testosterone (BT) (effect = −0.15, 95% CI = −0.21 to −0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7–0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol.

Conclusions:

The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.
Efficacy and safety of pan retinal photocoagulation combined with intravitreal anti-VEGF agents for high-risk proliferative diabetic retinopathy: A systematic review and meta-analysis
Authors: Fu Peng , Huang Yanling , Wan Xiaobo , Zuo Huiyi , Yang Yong , Shi Renshen , Huang Minli
Published: September 2023

Background:

High-risk proliferative diabetic retinopathy (HR-PDR) is the advanced stage of diabetic retinopathy progression with poor prior treatment efficacy and high rates of blindness. This meta-analysis aims to compare the efficacy and safety of pan retinal photocoagulation (PRP) combined with intravitreal anti-vascular endothelial growth factor (aVEGF) (PRP + aVEGF) versus PRP monotherapy in HR-PDR patients.

Methods:

A thorough search was performed through PubMed, Web of Science, EMBASE, and the Cochran Library from inception to December 18, 2022. Outcome measures included change in central macular thickness, best-corrected visual acuity, fluorescein angiography, incidence of undergoing vitrectomy, and adverse events during the follow-up period.

Results:

Eight studies (6 randomized controlled trials and 2 retrospective studies) with 375 eyes were included in this meta-analysis. There were no obvious differences in the changes of best-corrected visual acuity and fluorescein angiography between the PRP + aVEGF and PRP monotherapy groups. However, PRP + aVEGF group had a significant reduction in the change of central macula thickness (standard mean deviations = −1.44, 95%CI = −2.55 to −0.32, P = .01) and the rate of undergoing vitrectomy (odds ratio = 0.20, 95%CI = 0.05–0.83, P = .01). Additionally, the risks of vitreous hemorrhage and other complications were not significantly different between the 2 groups.

Conclusion subsections:

Our meta-analysis indicated that PRP + aVEGF might have potential benefits in the treatment of HR-PDR patients. However, given several limitations of this study, more research is needed to confirm our findings.
Comparison of efficacy of acupuncture-related therapy in the treatment of herpes zoster: A network meta-analysis of randomized controlled trials
Authors: Zhang Jingyu , Mou Qiujie , Wang Zhuxing , Huang Jinmoni , Zhang Yixin , Li Fuqi
Published: September 2023

Objective:

A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to evaluate the efficacy and safety of acupuncture-related therapy in the treatment of herpes zoster (HZ) and to provide a reference for the clinical treatment of herpes zoster.

Methods:

PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, VIP database, Wanfang Database, and SinoMED Chinese and English databases were systematically searched for RCTs on acupuncture-related therapy for HZ until February 2023. Literature screening, data extraction, and risk of bias assessment were performed independently by 2 researchers. R4.2.1 and Stata15.1 software were used for data analysis.

Results:

A total of 26 RCTs involving 1929 HZ patients were included, and the network meta-analysis results showed that acupotomy appeared to be most effective in terms of improving VAS scores and the time of incrustation; SUCRA cumulative probability ranking showed the best efficacy of bloodletting in improving efficiency and the time of ceasing new blisters, acupuncture in improving the time of decrustation, and moxibustion in reducing the incidence of postherpetic neuralgia (PHN).

Conclusions:

Through a comprehensive comparison of 9 different acupuncture therapies, acupotomy was the optimal treatment to improve VAS pain scores and the time of incrustation; bloodletting, acupuncture, fire needle, and moxibustion could be effective intervention measures to improve the time of ceasing new blisters and decrustation and reduce the incidence of PHN; Western medicine was closely related to adverse reactions. The conclusions need to be further verified due to the limitations of the study.
Risk factors for peripherally inserted central venous catheter-related complications in children: A retrospective cohort study
Authors: Wang Fang , Wang Yu , Liu Jingzhen
Published: September 2023

To explore the risk factors for peripherally inserted central venous catheter (PICC)-related complications in children. This retrospective study analyzed data collected from electronic medical records. A total of 584 patients with indwelling PICC treated between January 2019 and August 2021 were included in this study. According to the occurrence of PICC-related complications, the patients without PICC-related complications were included in the control group (n = 538) and those with PICC-related complications were included the observation group (n = 46). The risk factors for PICC-related complications were analyzed. Of the 584 patients with PICCs, 46 (7.88%) had PICC-related complications. Univariate analysis revealed significant differences in venipuncture (P < .001), oozing of blood from the puncture point (P < .001), indwelling time (P < .001), intravenous nutrient solution (P < .001), and catheter type (P = .003). Complications were used as dependent variables. The independent variables were vein puncture, blood oozing at the puncture point, indwelling time, intravenous nutrient solution, and catheter type. Multivariate logistic regression analysis revealed that the vein puncture (odds ratio [OR] 10.115, 95% confidence interval [CI] 5.034–20.323, P < .001), puncture point blood oozing (OR 9.217, 95% CI 3.860–22.004, P < .001), indwelling time (OR 6.390, 95% CI 3.527–10.972, P = .005), intravenous nutrient solution (OR 2.593, 95% CI 1.675–4.015, P < .001), and catheter type (OR 8.588, 95% CI 2.048–19.095, P = .013) were all risk factors for PICC-related complications in children. Venipuncture, oozing of blood from the puncture point, indwelling time, intravenous nutrient solution, and catheter type are risk factors for PICC-related complications in children. Significant attention should be paid to whether the puncture point is bleeding, the presence or absence of an intravenous nutrient solution, duration of catheterization, type of catheterization, and venipuncture. Additionally, preventive nursing measures should be implemented as soon as possible to reduce the risk of complications related to peripheral PICC.
Symptom-limited exercise capacity is associated with long-term survival
Authors: Huang Wei-Ming , Chang Hao-Chih , Chen Chiao-Nan , Huang Chi-Jung , Yu Wen-Chung , Cheng Hao-Min , Guo Chao-Yu , Chiang Chern-En , Chen Chen-Huan , Sung Shih-Hsien
Published: September 2023

The prognostic value of exercise capacity has been demonstrated in subjects with established cardiovascular diseases. We aim to evaluate the independence of exercise capacity measured by treadmill exercise test (TET) in predicting long-term outcomes among various comorbidities. This study was conducted from January 2003 to December 2012 in a tertiary medical center in Taiwan. Subjects referred for symptom-limited TET were recruited. Peak achieved metabolic equivalents (METs) were determined by treadmill grade and speed at peak exercise. The main outcomes were cardiovascular and all-cause mortality by linking to the National Death Registry. A total of 18,954 participants (57.8 ± 12.8 years, 62% men) achieved a mean peak METs of 9.2. Subjects in the lowest tertile of peak METs were older, had poorer renal function, lower hemoglobin, and more comorbidities. During a median follow-up of 4.3 years, there were 642 mortalities and 132 cardiovascular deaths. Peak METs significantly predicted cardiovascular death and all-cause mortality in the multivariable Cox regression models [hazard ratio (95% confidence intervals): 0.788 (0.660–0.940) and 0.835 (0.772–0.903), respectively]. The prognostic influence of peak METs consistently appeared in the subgroups, regardless of age, gender, body weight, comorbidities, use of beta-blockers, or the presence of exercise-induced ischemia. The fitness was more predictive of long-term outcomes in young or those with ischemic changes during TET (P for interaction: 0.035 and 0.018, respectively). The benefit of fitness was nonlinearly associated with long-term survival. The prognostic impacts of exercise capacity were universally observed in subjects with or without various comorbidities.
Network meta-analysis of acupuncture for tinnitus
Authors: Ji Lin , Zhang Haopeng , Wang Lihua , Yin Ziming , Cen Jingtu , Guo Yu
Published: September 2023

Objective:

To provide evidence for medical management of tinnitus based on an assessment of the evidence concerning the effectiveness of acupuncture as a treatment for tinnitus using network meta-analysis (NMA).

Methods:

We conducted a systematic literature review by searching 8 national and international databases (inception to February 2023) for randomized controlled trials (RCTs) for tinnitus. Only RCTs that recruited participants aged over 18 and diagnosed with tinnitus, and that evaluated acupuncture or acupuncture in combination with conventional western medical therapy were included. We used response rate and tinnitus handicap inventory (THI) to examine efficacy. We conducted NMA with random effects, and the rate ratio or mean difference with its 95% credible interval was calculated. In addition, we ranked all treatments via their SUCRA and assessed the quality of evidence according to the GRADE criteria.

Results:

A total of 2575 patients were included in the study. The main findings of the current NMA were that acupoint injection combined with warm acupuncture was the most effective for response rate, followed by warm acupuncture and acupoint injection combined with western medical treatment. Acupuncture combined with western medical treatment was the most effective for THI, followed by electroacupuncture combined with warm acupuncture and acupuncture combined with moxibustion.

Conclusion:

Acupuncture seems to be a better trend treatment for tinnitus. Further rigorous RCT studies that include direct comparisons for different acupuncture-related treatments are encouraged to provide the most promising evidence for patients with tinnitus.

Protocol registration:

CRD42023398745.
Identification of a basement membrane-related genes signature to predict prognosis, immune landscape and guide therapy in gastric cancer
Authors: Liu Zhi-Yang , Xin Lin
Published: September 2023

The basement membrane is an essential defense against cancer progression and is intimately linked to the tumor immune microenvironment. However, there is limited research comprehensively discussing the potential application of basement membrane-related genes (BMRGs) in the prognosis evaluation and immunotherapy of gastric cancer (GC). The RNA-seq data and clinical information of GC patients were collected from the TCGA and GEO database. Prognosis-associated BMRGs were filtered via univariate Cox regression analysis. The 4-BMRGs signatures were constructed by lasso regression. Prognostic predictive accuracy of the 4-BMRGs signature was appraised with survival analysis, receiver operating characteristic curves, and nomogram. Gene set enrichment analysis (GSEA), gene ontology, and gene set variation analysis were performed to dig out potential mechanisms and functions. The Estimate algorithm and ssGSEA were used for assessing the tumor microenvironment and immunological characteristics. Identification of molecular subtypes by consensus clustering. Drug sensitivity analysis using the “pRRophetic” R package. Immunotherapy validation with immunotherapy cohort. A 4-BMRGs signature was constructed, which could excellently predict the GC patient prognosis (5-year AUC value of 0.873). Kaplan–Meier and Cox regression analyses showed that the 4-BMRGs signature was an OS-independent prognostic factor, and that higher risk scores were associated with shorter OS. The high-risk subgroup exhibits a higher abundance of immune cell infiltration, such as macrophages. Additionally, we observed a strong correlation between 2 BMRGs (LUM, SPARC) and immune cells such as CD8 + T cells and macrophages. The high-risk subgroup appears to be more sensitive to Axitinib, DMOG, Gemcitabine and Docetaxel by pRRophetic analysis. Furthermore, the validation of the cohort that received immune therapy revealed that patients in the high-risk group who underwent immune checkpoint inhibitor treatment exhibited better response rates. Pan-cancer analysis also shows that risk scores are strongly associated with immune and carcinogenic pathways. The 4-BMRGs signature has demonstrated accuracy and reliability in predicting the GC patient’s prognosis and could assist in the formulation of clinical strategies.
Transitional zone prostate cancer: Performance of texture-based machine learning and image-based deep learning
Authors: Lee Myoung Seok , Kim Young Jae , Moon Min Hoan , Kim Kwang Gi , Park Jeong Hwan , Sung Chang Kyu , Jeong Hyeon , Son Hwancheol
Published: September 2023

This study is aimed to explore the performance of texture-based machine learning and image-based deep-learning for enhancing detection of Transitional-zone prostate cancer (TZPCa) in the background of benign prostatic hyperplasia (BPH), using a one-to-one correlation between prostatectomy-based pathologically proven lesion and MRI. Seventy patients confirmed as TZPCa and twenty-nine patients confirmed as BPH without TZPCa by radical prostatectomy. For texture analysis, a radiologist drew the region of interest (ROI) for the pathologically correlated TZPCa and the surrounding BPH on T2WI. Significant features were selected using Least Absolute Shrinkage and Selection Operator (LASSO), trained by 3 types of machine learning algorithms (logistic regression [LR], support vector machine [SVM], and random forest [RF]) and validated by the leave-one-out method. For image-based machine learning, both TZPCa and BPH without TZPCa images were trained using convolutional neural network (CNN) and underwent 10-fold cross validation. Sensitivity, specificity, positive and negative predictive values were presented for each method. The diagnostic performances presented and compared using an ROC curve and AUC value. All the 3 Texture-based machine learning algorithms showed similar AUC (0.854–0.861)among them with generally high specificity (0.710–0.775). The Image-based deep learning showed high sensitivity (0.946) with good AUC (0.802) and moderate specificity (0.643). Texture -based machine learning can be expected to serve as a support tool for diagnosis of human-suspected TZ lesions with high AUC values. Image-based deep learning could serve as a screening tool for detecting suspicious TZ lesions in the context of clinically suspected TZPCa, on the basis of the high sensitivity.
The value of hematocrit for predicting bronchopulmonary dysplasia in very low birth weight preterm infants
Authors: Wang Xuesong , Wang Shushu , Chen Mingwu , Lv Yong , Chen Xueyu , Yang Chuanzhong
Published: September 2023

To determine hematocrit (HCT) and to identify independent risk factors for predicting bronchopulmonary dysplasia (BPD) in preterm infants with very low birth weight (VLBW) infants. This retrospective study included 296 premature infants with VLBW in the neonatal intensive care unit of the First Affiliated Hospital of the University of Science and Technology of China between January 2015 and December 2019. Maternal pregnant information and clinical information as well as hematological parameters of preterm babies were collected and compared. Then the maximum area under the curve of receiver operating characteristic curve was developed to estimate the predictive indicator in the blood. Finally, differential variables together with the predictive index were screened for multiple logistic regression analysis to determine independent prognostic factors for BPD. Infants were divided into a BPD group (134 cases) and a non-BPD group (162 cases). The area under the curve of HCT at postnatal 1 week was 0.737 with the sensitivity of 52.30 % and the specificity of 86.00%. Birth weight (BW) <1.12 kg, gestational age <28.4 weeks, newborn respiratory distress syndrome, mechanical ventilation ≥ 7 days, ventilation associated pneumonia, patent arterial duct, PaO2/FiO2 <300 mm Hg and HCT <0.455 at postnatal 1 week were risk factors for BPD of VLBW infants. HCT levels below 0.455 at 1 week after birth serve as a valuable indicator for the potential development of BPD.
Clinical characteristics of COVID-19 rebound after nirmatrelvir-ritonavir or molnupiravir therapy: A prospective cohort study
Authors: Han Jaijun , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Chang Euijin , Kim Sung-Han
Published: September 2023

The clinical characteristics of the rebound phenomenon after antiviral therapy in patients with Coronavirus disease-2019 (COVID-19) are largely unknown. There are few data comparing the rebound phenomenon after molnupiravir therapy to that after nirmatrelvir-ritonavir therapy. We investigated the incidence and risk factors associated with COVID-19 rebound after nirmatrelvir-ritonavir or molnupiravir therapy during the Omicron era. This prospective cohort study enrolled patients with mild-to-moderate COVID-19 who received nirmatrelvir-ritonavir or molnupiravir. We conducted weekly questionnaires of symptom scores from day 0 to day 28, with an additional day when patients experienced reappearing symptoms. We defined COVID-19 rebound as when patients experienced a 50% increase in symptom scores compared to the lowest symptom score between days 0 and 14. Among the 150 patients, 93 (62%) and 57 (38%) received nirmatrelvir-ritonavir therapy and molnupiravir, respectively. Of these, 11 patients (7.3%; 95% CI, 3.1–11.5) experienced COVID-19 rebound. The median duration from antiviral therapy to rebound was 12 days. Patients with clinical rebound had a higher symptom score at antiviral therapy initiation than those without (median, 5 vs 4; P = .02). There was no significant difference in the clinical rebounds associated with nirmatrelvir-ritonavir and molnupiravir therapy (5.4% vs 10.5%; P = .39). Approximately one-tenth of patients with mild-to-moderate COVID-19 who received antiviral therapy experienced rebound phenomena after treatment. Regardless of antiviral therapy type, high initial symptom scores were associated with a more frequent rebound phenomenon.
Molecular targets and mechanisms of Guanxinning tablet in treating atherosclerosis: Network pharmacology and molecular docking analysis
Authors: Niu Chaofeng , Zhang Peiyu , Zhang Lijing , Lin Dingfeng , Lai Haixia , Xiao Di , Liu Yong , Zhuang Rui , Li Meng , Ma Liyong , Ye Jiaqi , Pan Yi
Published: September 2023

Background:

Guanxinning tablet (GXNT), a Chinese patent medicine, is composed of salvia miltiorrhiza bunge and ligusticum striatum DC, which may play the role of endothelial protection through many pathways. We aimed to explore the molecular mechanisms of GXNT against atherosclerosis (AS) through network pharmacology and molecular docking verification.

Methods:

The active ingredients and their potential targets of GXNT were obtained in traditional Chinese medicine systems pharmacology database and analysis platform and bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. DrugBank, TTD, DisGeNET, OMIM, and GeneCards databases were used to screen the targets of AS. The intersection targets gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were performed in DAVID database. GXNT-AS protein-protein interaction network, ingredient-target network and herb-target-pathway network were constructed by Cytoscape. Finally, we used AutoDock for molecular docking.

Results:

We screened 65 active ingredients of GXNT and 70 GXNT-AS intersection targets. The key targets of protein-protein interaction network were AKT1, JUN, STAT3, TNF, TP53, IL6, EGFR, MAPK14, RELA, and CASP3. The Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling pathway were the main pathways. The ingredient-target network showed that the key ingredients were luteolin, tanshinone IIA, myricanone, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone. The results of molecular docking showed that tanshinone IIA, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone all had good binding interactions with AKT1, EGFR and MAPK14.

Conclusion:

The results of network pharmacology and molecular docking showed that the multiple ingredients within GXNT may confer protective effects on the vascular endothelium against AS through multitarget and multichannel mechanisms. AKT1, EGFR and MAPK14 were the core potential targets of GXNT against AS.
Is ulnar shortening osteotomy or the wafer procedure better for ulnar impaction syndrome?: A systematic review and meta-analysis
Authors: Ha Joong Won , Kwon Young Woo , Lee Sujung , Lim Hyunsun , Lee Jinho , Lim Chae Kwang , Lee Jun-Ku
Published: September 2023

Background:

Wrist pain on the ulnar side is often caused by ulnar impaction syndrome (UIS). Idiopathic UIS requires surgical treatment when conservative treatment fails. The 2 main surgical procedures used are the wafer procedure and ulnar shortening osteotomy (USO) of the metaphysis or diaphysis. This review aimed to analyze comparative studies of the 2 procedures in UIS to determine clinical outcomes and complications.

Methods:

One prospective and 5 retrospective comparison trials were retrieved from the PubMed, Embase, and Cochrane Library databases. The primary outcomes were treatment effectiveness; pain visual analog scale (VAS), disabilities of the arm, shoulder, and hand (DASH) score, Mayo wrist, and Darrow scores. The incidence of postoperative complications formed the secondary outcome.

Results:

The selected studies included 107 patients who underwent the wafer procedure (G1) and 117 patients who underwent USO (G2). The wafer procedure had the benefits of less postoperative immobilization and an early return to work. However, there were no significant differences in the postoperative pain improvement and functional scores. All 6 studies reported high total complication rates and reoperation with USO. The most frequent complication was implant-related discomfort or irritation; subsequent plate removal was the most common reason for a secondary operation.

Conclusions:

There was no difference in pain improvement or the postoperative functional score between the groups. Nevertheless, postoperative complications were the major pitfalls of USO. As the specialized shortening system advances further, a high-level study will be necessary to determine the surgical option in UIS.
HMBS gene mutations and hydroxymethylbilane synthase activity in acute intermittent porphyria: A systematic review
Authors: Li Shuang , Lei Jia-Jia , Dong Bai-Xue , Ren Yi , Yang Jing
Published: September 2023

Background:

Acute intermittent porphyria (AIP) is caused by a partial deficiency of hydroxymethylbilane synthase and affects heme biosynthesis. Mutations in the HMBS gene result in HMBS deficiency. AIP is a rare disease, and there been insufficient studies on it. This report describes the molecular epidemiology of HMBS gene defects and hydroxymethylbilane synthase activity levels in classical AIP.

Methods:

Databases of PubMed, CNKI, and Wang Fang Database were searched for eligible studies to investigate HMBS gene mutations in peripheral blood samples and HMBS activity in erythrocytes of patients with classical AIP. Relevant studies published up to July 15, 2023, from several databases were independently searched and selected by 2 reviewers. Accuracy data and relevant information were extracted from each eligible study by 2 independent researchers and analyzed using statistical software.

Results:

After pooling the accuracy data from 232 patients of the 15 eligible studies, 90.5% (210/232) of AIP patients had decreased erythrocyte hydroxymethylbilane synthase activity (<70%), and 96 different mutations were identified in 232 patients, including 33 missense (34.4%), 27 splice (28.1%), 19 deletion (19.8%), 8 nonsense (8.3%), 9 insertion (9.4%) mutations. Residual enzyme activities (%) for different groups of type were expressed using mean and 95% confidence interval (95% CI): missense (51.2, 48.5–53.9), splice (57.5, 52.0–59.1), deletion (54.9, 50.7–59.1), nonsense (52.2, 44.4–60.0), insertion (53.2, 47.4–59.0), group analysis P = .17. Subgroups of missense mutations, domain 1 (50.2, 46.0–54.4), domain 2 (52.8, 49.1–56.4), and domain 3 (49.2, 38.3–60.0), Subgroup analysis, P = .62.

Conclusion:

Different mutation types and mutation positions are not associated with the level of hydroxymethylbilane synthase activity. Erythrocyte hydroxymethylbilane synthase activity is often reduced to half of normal in patients with AIP, and the enzyme activity assay has a high diagnostic value in AIP. AIP is highly molecularly heterogeneous, with missense mutations being the most common, followed by splice mutations. R173W and G111R are high-frequency mutations and have been found in multiple families from different countries.