bluuebunny/crossref_metadata_2025 huggingface dataset:
Network regression analysis in transcriptome-wide association studies
Authors: Jin Xiuyuan , Zhang Liye , Ji Jiadong , Ju Tao , Zhao Jinghua , Yuan Zhongshang
Published: August 2022

Background

Transcriptome-wide association studies (TWASs) have shown great promise in interpreting the findings from genome-wide association studies (GWASs) and exploring the disease mechanisms, by integrating GWAS and eQTL mapping studies. Almost all TWAS methods only focus on one gene at a time, with exception of only two published multiple-gene methods nevertheless failing to account for the inter-dependence as well as the network structure among multiple genes, which may lead to power loss in TWAS analysis as complex disease often owe to multiple genes that interact with each other as a biological network. We therefore developed a Network Regression method in a two-stage TWAS framework (NeRiT) to detect whether a given network is associated with the traits of interest. NeRiT adopts the flexible Bayesian Dirichlet process regression to obtain the gene expression prediction weights in the first stage, uses pointwise mutual information to represent the general between-node correlation in the second stage and can effectively take the network structure among different gene nodes into account.

Results

Comprehensive and realistic simulations indicated NeRiT had calibrated type I error control for testing both the node effect and edge effect, and yields higher power than the existed methods, especially in testing the edge effect. The results were consistent regardless of the GWAS sample size, the gene expression prediction model in the first step of TWAS, the network structure as well as the correlation pattern among different gene nodes. Real data applications through analyzing systolic blood pressure and diastolic blood pressure from UK Biobank showed that NeRiT can simultaneously identify the trait-related nodes as well as the trait-related edges.

Conclusions

NeRiT is a powerful and efficient network regression method in TWAS.
What is the best technic to dislodge Staphylococcus epidermidis biofilm on medical implants?
Authors: Moris Vivien , Lam Mylan , Amoureux Lucie , Magallon Arnaud , Guilloteau Adrien , Maldiney Thomas , Zwetyenga Narcisse , Falentin-Daudre Céline , Neuwirth Catherine
Published: August 2022

Background

Bacterial biofilm can occur on all medical implanted devices and lead to infection and/or dysfunction of the device.

In this study, artificial biofilm was formed on four different medical implants (silicone, piccline, peripheral venous catheter and endotracheal tube) of interest for our daily clinical and/or research practice. We investigated the best conventional technic to dislodge the biofilm on the implants and quantified the number of bacteria. Staphylococcus epidermidis previously isolated from a breast implant capsular contracture on a patient in the university hospital of Dijon was selected for its ability to produce biofilm on the implants. Different technics (sonication, Digest-EUR®, mechanized bead mill, combination of sonication plus Digest-EUR®) were tested and compared to detach the biofilm before quantifying viable bacteria by colony counting.

Results

For all treatments, the optical and scanning electron microscope images showed substantial less biofilm biomass remaining on the silicone implant compared to non-treated implant.

This study demonstrated that the US procedure was statistically superior to the other physical treatment: beads, Digest-EUR® alone and Digest-EUR® + US (p < 0.001) for the flexible materials (picc-line, PIV, and silicone). The number of bacteria released by the US is significantly higher with a difference of 1 log on each material. The result for a rigid endotracheal tube were different with superiority for the chemical treatment dithiothreitol: Digest-EUR®. Surprisingly the combination of the US plus Digest-EUR® treatment was consistently inferior for the four materials.

Conclusions

Depending on the materials used, the biofilm dislodging technique must be adapted. The US procedure was the best technic to dislodge S. epidermidis biofilm on silicone, piccline, peripheral venous catheter but not endotracheal tube. This suggested that scientists should compare themselves different methods before designing a protocol of biofilm study on a given material.
Implication of quantifying nitrate utilization and CO2 assimilation of Brassica napus plantlets in vitro under variable ammonium/nitrate ratios
Authors: Zhang Kaiyan , Wu Yanyou , Su Yue , Li Haitao
Published: August 2022

Background

Plantlets grown in vitro with a mixed nitrogen source utilize sucrose and CO2 as carbon sources for growth. However, it is very difficult to obtain the correct utilization proportions of nitrate, ammonium, sucrose and CO2 for plantlets. Consequently, the biological effect of ammonium/nitrate utilization, the biological effect of sucrose/CO2 utilization, and the ammonium/nitrate use efficiency for new C input derived from CO2 assimilation/sucrose utilization are still unclear for plantlets.

Results

The bidirectional stable nitrogen isotope tracer technique quantified the proportions of assimilated nitrate and ammonium in Brassica napus plantlets grown at different ammonium/nitrate ratios. The utilization proportions of sucrose and CO2 could be quantified by a two end-member isotope mixing model for Bn plantlets grown at different ammonium/nitrate ratios. Under the condition that each treatment contained 20 mM ammonium, the proportion of assimilated nitrate did not show a linear increase with increasing nitrate concentration for Bn plantlets. Moreover, the proportion of assimilated CO2 did not show a linear relationship with the nitrate concentration for Bn plantlets. Increasing the nitrate concentration contributed to promoting the assimilation of ammonium and markedly enhanced the ammonium utilization coefficient for Bn plantlets. With increasing nitrate concentration, the amount of nitrogen in leaves derived from nitrate assimilation increased gradually, while the nitrate utilization coefficient underwent no distinct change for Bn plantlets.

Conclusions

Quantifying the utilization proportions of nitrate and ammonium can reveal the energy efficiency for N assimilation in plantlets grown in mixed N sources. Quantifying the utilization proportion of CO2 contributes to evaluating the photosynthetic capacity of plantlets grown with variable ammonium/nitrate ratios. Quantifying the utilization proportions of nitrate, ammonium, sucrose and CO2 can reveal the difference in the ammonium/nitrate use efficiency for new C input derived from CO2 assimilation/sucrose utilization for plantlets grown at variable ammonium/nitrate ratios.
Procedural analgesic interventions in China: a national survey of 2198 hospitals
Authors: Wang Yafeng , Xu Feng , Zhao Shuai , Han Linlin , Huang Shiqian , Zhu Hongyu , Ding Yuanyuan , Ma Lulin , Zhao Wenjing , Zhang Tianhao , Chen Xiangdong ,   Pain Group of Chinese Society of Anesthesiology, Feng Yi , Dong Tieli , Xu Zhonghuang , Lv Yan , Hua Zhen , Liu Yanhong , Bai Yanyan , Cao Song , Chen Yajun , Du Jianhua , Fan Yinghui , Han Guang , He Nong , He Xingying , He Yongjin , Hu Yanhui , Li Yanhua , Liu Dezhao , Liu Ping , Liu Silan , Ma Danxu , Ma Minyu , Ren Fei , Shang You , Shen Xiaofeng , Song Jie , Tie Muer , Wang Chunhui , Wang Feng , Wang Haitang , Wang Huishu , Wang Tiancheng , Wang Yaping , Wu Wei , Xu Hua , Xue Zhaoxia , Yu Lingzhi , Zhan Leyun , Zhang Dong , Zhang Jinjun , Wu Duozhi , Yang Dong
Published: August 2022

Background

Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies.

Methods

Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology.

Results

Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3—11.4] cases per day, with 7.3 [3.2—13.6] performed in Grade III hospitals and 3.4 [1.8—6.8] performed in Grade II hospitals (z = -7.065, p < 0.001).

Conclusions

Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions.
Effects of adaptive left bundle branch–optimized cardiac resynchronization therapy: a single centre experience
Authors: Feng Xiang-Fei , Yang Ling-Chao , Zhao Yan , Yu Yi-Chi , Liu Bo , Li Yi-Gang
Published: August 2022

Background

Adaptive cardiac resynchronization therapy (aCRT) is associated with improved clinical outcomes. Left bundle branch area pacing (LBBAP) has shown encouraging results as an alternative option for aCRT. A technique that can be accomplished effectively using LBBAP combined with coronary venous pacing (LOT-aCRT). We aimed to assess the feasibility and outcomes of LOT-aCRT.

Methods

LOT-aCRT, capable of providing two pacing modes, LBBAP alone or LBBAP combined with LV pacing, was attempted in patients with CRT indications. Patients were divided into two groups: those with LBBAP and LV pacing (LOT-aCRT) and those with conventional biventricular pacing (BVP-aCRT).

Results

A total of 21 patients were enrolled in the study (10 in the LOT-aCRT group, 11 in the BVP-aCRT group). In the LOT-aCRT group, the QRS duration (QRSd) via BVP was narrowed from 158.0 ± 13.0 ms at baseline to 132.0 ± 4.5 ms (P = 0.019) during the procedure, and further narrowed to 123.0 ± 5.7 ms (P < 0.01) via LBBAP alone. After the procedure, when LOT-aCRT implanted and worked, QRSd was further changed to 121.0 ± 3.8 ms, but the change was not significant (P > 0.05). In the BVP-aCRT group, BVP resulted in a significant reduction in the QRSd from 176.7 ± 19.7 ms at baseline to 133.3 ± 8.2 ms (P = 0.011). However, compared with LOT-aCRT, BVP has no advantage in reducing QRSd and the difference was statistically significant (P < 0.01). During 9 months of follow-up, patients in both groups showed improvements in the LVEF and NT-proBNP levels (allP < 0.01). However, compared with BVP-aCRT, LOT-aCRT showed more significant changes in these parameters (P < 0.01).

Conclusions

The study demonstrates that LOT-aCRT is clinically feasible in patients with systolic heart failure and LBBB. LOT-aCRT was associated with significant narrowing of the QRSd and improvement in LV function.
Albumin infusion in hospitalized patients with acute heart failure: a retrospective cohort study
Authors: Wang Lei , Zhao Yun-Tao
Published: August 2022

Background

Heart failure is frequently associated with hypoalbuminaemia and poor prognosis. Acute heart failure (AHF) patients are commonly treated with intravenous albumin to improve osmotic pressure and haemodynamics. However, the effects of exogenous albumin supplementation on the fatality rate of AHF patients have not yet been demonstrated. Therefore, the present study strived to examine the impacts of albumin injections on the mortality rate of patients with AHF.

Methods

This retrospective cohort study evaluated the clinical outcomes of all consecutive hospitalized patients. Data were collected from medical records. The primary end-point was a composite of intubation, emergency renal replacement, or mortality in a time-to-event analysis. An inverse probability-weighted multivariable Cox model was used to compare outcomes between patients who were treated with albumin and those who were not based on the propensity score.

Results

Among the 1420 consecutive patients hospitalized in our hospital with acute decompensated heart failure between 1 January 2017 and 27 February 2021, 382 were excluded, 337 (32.5%) were administered albumin (median treatment dose of 29.0 g), and 701 (67.5%) were not. The albumin exposure varied by body mass index, age group, previous diagnoses, clinical signs and symptoms, laboratory tests, and use of other drugs in the unmatched sample. The patients receiving albumin exhibited a lower serum albumin level at baseline in contrast with those who were not treated with albumin (median, 37.3 g/L vs. 31.7 g/L, respectively). Overall, primary end-point events occurred in 357 patients (34.4%) (79 died without being intubated or during an emergency renal replacement therapy, 118 were intubated and 160 had an emergency renal replacement therapy). In the inverse probability weighted multivariable analysis based on the propensity score, albumin use was not significantly associated with the composite primary end-point (hazard ratio, 1.05; 95% confidence interval, 0.75–1.47).

Conclusion

In this observational study of AHF patients hospitalized in our hospital, the administration of albumin did not show a relationship with either a greatly reduced or aggregated risk of the composite end-point of intubation, emergency renal replacement therapy, or death. Therefore, randomized controlled trials of albumin administration are needed for patients with AHF.
Serum and salivary tissue transglutaminase IGA (tTG-IGA) level in celiac patients
Authors: Ajdani Mehran , Mortazavi Nazanin , Besharat Sima , Mohammadi Saeed , Amiriani Taghi , Sohrabi Ahmad , Norouzi Alireza , Edris Ghezeljeh
Published: August 2022

Background

Celiac disease (CD) is a genetically determined autoimmune disease triggered by gluten consumption. Patients with these conditions have intraepithelial lymphocytosis, crypt hyperplasia, and severe intestinal atrophy. Gluten elimination is the only way to reduce this chronic inflammation. The diagnosis of CD is usually made by analyzing anti-tTG, anti-DGP, or EMA serological tests, and it is confirmed by biopsy of the duodenum.

In people with CD, xerostomia or dry mouth is a common complication. This condition causes the salivary glands to malfunction and, in turn, may result in oral plaque and periodontal disease.

By comparing salivary and serum levels of tissue transglutaminase IgA (tTG-IgA), this study aims to suggest a non-invasive method for diagnosis of CD. Furthermore, the present study evaluates the severity of xerostomia symptoms in people with CD.

Methods

In this case–control study, participants were patients referred to the internal ward of Sayyad Shirazi hospital. The control group was selected from healthy people who attended Gorgan Dental College.

In this study, an analysis of serum was performed following consent from patients. This was followed by a salivary test, and the results of both tests were compared.

The Xerostomia Inventory questionnaire was also used to determine the severity of xerostomia. As part of this study, examination of factors such as total protein concentration of saliva, albumin concentration, amylase level, pH, sodium, calcium, potassium, phosphorus, and interleukin (6, 18, and 21) were conducted.

Results

A total of 78 people were studied (aged 15 to 68), 26 were male (33.3%) and 52 were female (66.7%). In comparisons of the serum and saliva of people with and without CD, the level of amylase was higher in the latter group. The average levels of IL-6، IL-18 ،IL-21, and salivary and serum tTG were higher in people with CD. Additionally, CD patients were more likely to develop xerostomia.

Conclusion

Study findings showed that CD can reduce certain salivary enzymes and elements, as well as increase inflammatory cytokines, salivary, and serum tTG.

The management of dry mouth should also be recommended for celiac disease patients in order to prevent its complications.
Awareness and treatment of chronic hepatitis B in Malaysia-findings from a community-based screening campaign
Authors: Lim Zhuo-zhi , Teo Jau shya , Tan Ah-Choon , Lim Teck Onn
Published: August 2022

Introduction

In 2016 the World Health Organization (WHO) had adopted a global strategy to eliminate Hepatitis B (HBV) by 2030 through five core interventions. One of which is the “cascade of care”, the continuum of services that persons with chronic Hepatitis B Virus (HBV) should receive as they progress from screening to diagnosis to treatment to chronic care. We determined the prevalence of the awareness and treatment of chronic HBV in Malaysia based on a large sample data from a screening campaign.

Methods

A total of 10,436 subjects participated in the HBV screening campaign organized by the Hepatitis Free Pahang Malaysia (HFP). Between in 2018 and 2019, HFP organized a total of 109 health fairs in partnership with local non-governmental organizations (NGO) to conduct HBV screening mostly in small towns and villages largely in the state of Pahang. All screen-positive subjects were recalled to undergo laboratory-based HBsAg and HBV DNA tests. Patients with confirmed chronic HBV were referred to local health services, while continued being monitored by HFP.

Results

We estimated 13.1% of Malaysian adults aged 20 or older with chronic HBV were aware of their HBV status, and of those only 0.7% had received prior anti-viral treatment, but among those with baseline HBV DNA level > 20,000 IU/ml, 15.6% were subsequently treated. Tenofovir disoproxil fumarate was the only medicine used on all treated patients.

Conclusion

Few Malaysian adults with HBV were aware of their infection and even less received anti-viral therapy. Concerted public health efforts are urgently needed to improve HBV screening and care cascade in order to meet WHO’s targets for HBV elimination.
Significance of levothyroxine treatment on serum lipid in pregnant women with subclinical hypothyroidism
Authors: Yang Yuxi , Yuan Huabing , Wang Xueran , Zhang Zheng , Liu Ruixia , Yin Chenghong
Published: August 2022

Background

There is no consensus reference range for serum lipid levels during pregnancy. The benefit of levothyroxine (L-T4) on serum lipid levels are unclear among pregnant women with subclinical hypothyroidism (SCH).

Objective

To determine the recommended reference ranges for serum lipid concentrations during pregnancy and effects of L-T4 treatment on serum lipids in pregnant women with SCH.

Design

Cohort study.

Methods

A analysis of 20,365 women in the first trimester was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University during 2018–2020. After excluding women with adverse pregnancy outcomes, we determined the reference range of serum lipid in the first and third trimesters of pregnancy by using median and quartile to determine appropriate percentiles. Next, we divided into three groups as follows: SCH L-T4 treatment group (n = 319), SCH non-intervention group (n = 103) and the control group(n = 9598).

Results

The recommended reference range for serum lipids in the first trimester of pregnancy should be: TC < 5.33 mmol/L, TG < 1.73 mmol/L, LDL-C < 3.12 mmol/L and HDL-C > 1.1 mmol/L, and in third trimester of pregnancy should be: TC < 8.47 mmol/L, TG < 4.86 mmol/L, LDL-C < 5.3 mmol/L and HDL-C > 1.34 mmol/L.

There are significant differences in TC and LDL-C levels between SCH treatment group and SCH non-intervention Group (P = 0.043, P = 0.046; respectively).

Conclusions

We determine the recommended reference ranges for serum lipid concentrations during pregnancy. TC and LDL-C levels in pregnant women with SCH could improve after L-T4 treatment.
Poor treatment responses were related to poor outcomes in pediatric B cell acute lymphoblastic leukemia with KMT2A rearrangements
Authors: Wen Jinquan , Zhou Min , Shen Yali , long Yueting , Guo Yuxia , Song Lin , Xiao Jianwen
Published: August 2022

Background

The KMT2A gene, formerly named the MLL gene, is rearranged (KMT2Ar) in 70–75% of infants, 5–6% of children and 10–15% of adult patients with B cell acute lymphoblastic leukemia (B-ALL). The outcome after chemotherapy of pediatric cases remains poor, and only a few studies have investigated the clinical and laboratory features, treatment response and prognosis in Chinese populations.

Methods

A total of 48 B-ALL children with KMT2Ar were enrolled in the study, and clinical and laboratory data were collected and analyzed by age group. The relationship between prognosis and traditional risk factors and treatment response was investigated for these patients who received chemotherapy.

Results

The 48 enrolled patients included 28 males and 20 females; 18 (37.50%) or 30 (62.50%) patients were an age of < 12 m (infant B-ALL) or of > 12 m at onset. An initial WBC count of 300 × 109/L was detected in 7 (14.58%) patients; testicular leukemia (TL) or central nervous system involvement was found in 5 (10.41%) or 3 (6.25%) patients, respectively. Statistical differences were not found in the age groups of sex or initial WBC count, whereas TL was more common in the infant group (P < 0.05). 11q23 was detected in 18 patients; KMT2Ar was detected in 46 (95.83%) or 45 (93.75%) patients by FISH or multiplex RT–PCR technology, respectively; RNA-seq data were obtained for 18 patients, and 3 patients with uncommon KMT2Ar were identified. KMT2A-AFF1, KMT2A-MLLT3 and KMT2A-MLLT1 were the most common transcripts. Statistical differences were not found in treatment response by age groups, including dexamethasone induction, bone marrow (BM) smear status and minimal residual disease (MRD) level at different time points (TP), treatment-related mortality (TRM), or complete remission (CR) rate (P > 0.05); MRD levels monitored by FCM or PCR were unequal at the same TP. Four patients died of treatment, and TRM was 8.33%; 40 patients achieved CR, and the CR rate for the cohort was 83.33%. Seven patients quit, 15 patients relapsed, and the 5 yr cumulative relapse rate was 59.16 ± 9.16%; the 5 yr prospective EFS (pEFS) for patients who were included or excluded from the TRM group was 36.86 ± 8.48% or 40.84 ± 9.16%, respectively. Multivariate analysis for prognosis and hazard ratio was performed for 37 patients without TRM and revealed that an initial WBC count of > 300 × 109/L and a positive level of FCM-MRD were strongly related to a poor outcome for B-ALL patients with KMT2Ar (P < 0.05).
Systematic review of circulating MICRORNAS as biomarkers of cervical carcinogenesis
Authors: Nascimento Neila Pierote Gaspar , Gally Thais Borges , Borges Grasiely Faccin , Campos Luciene Cristina Gastalho , Kaneto Carla Martins
Published: August 2022

Background

Cervical cancer is a preventable disease, but it is a major public health problem despite having a good prognosis when diagnosed early. Although the Pap smear has led to huge drops in rates of cervical cancer and death from the disease, it has some limitations, making new approaches necessary for early diagnosis and biomarkers discovery. MiRNAs have been considered a new class of non-invasive biomarkers and may have great clinical value for screening early-stage cervical intraepithelial neoplasia. Well-designed studies have emerged as a necessary strategy for the identification of miRNAs that could be used safely and reliably for a differential diagnosis. This review aims to provide an up-to-date perspective on the assessment of circulating miRNA expression from precursor lesions to cervical cancer, identifying circulating miRNAs or specific miRNA signatures that can be used as potential biomarkers of different stages of cervical carcinogenesis.

Methods

A systematic review was performed and searches were conducted in the PubMed, LILACS, and Scopus electronic databases.

Results

Most studies involved Chinese ethnic women and searched for circulating miRNAs in serum samples. Thirty three microRNAs were evaluated in the eligible studies and 17 (miR-196a, miR-16-2, miR-497, miR-1290, miR-425-5p, hsa-miR- 92a, miR-1266, miR-9, miR-192, miR-205, miR-21, miR-152, miR-15b, miR-34a, miR-218, miR-199a-5p and miR-155-5p) showed up-regulation in women with precursor lesion and cervical cancer and 16 microRNAs showed decreased expression in these same groups of women compared to healthy controls (miR-195, miR-2861, miR-145, miR-214, miR-34a, miR-200a, let-7d-3p, miR-30d-5p, miR-638, miR-203a-3p, miR-1914-5p, miR-521, miR-125b, miR-370, miR-218 and miR-100).

Conclusion

Therefore, defining promising circulating miRNAs or specific miRNA signatures of biological fluid samples can be useful for the screening, diagnosis, prognosis and clinical monitoring of women undergoing cervical carcinogenesis, but greater standardization of studies seems to be necessary for greater consolidation of information.
Serum 25-hydroxyvitamin D and cancer-related fatigue: associations and effects on depression, anxiety, functional capacity and health-related quality of Life in breast cancer survivors during adjuvant endocrine therapy
Authors: Custódio Isis Danyelle Dias , Nunes Fernanda Silva Mazzutti , Lima Mariana Tavares Miranda , de Carvalho Kamila Pires , Alves Débora Santana , Chiaretto Juliana Freitas , Canto Paula Philbert Lajolo , Paiva Carlos Eduardo , de Paiva Maia Yara Cristina
Published: August 2022

Background

The adjuvant treatment with Aromatase Inhibitor (AI) is considered standard of care for postmenopausal breast cancer (BC) women with hormone receptor-positive (HR +), however, it often causes adverse effects such as cancer-related fatigue (CRF). The high prevalence of vitamin D deficiency in postmenopausal women who start adjuvant AI supports the hypothesis that hypovitaminosis D would be one of the biological explanations for toxicity of AI. This study aimed to identify the relationship between 25-hydroxyvitamin D [25(OH)D] and CRF, and to analyze their associations and effects on depression, anxiety, functional disability, muscle/joint aches and HRQL.

Methods

This prospective study included 89 postmenopausal women diagnosed with HR + early BC in adjuvant endocrine therapy with AI. Anthropometric and body composition assessments were performed, as well as dietary assessments by application of 24-h dietary recall, at three time points, totaling 24 months of follow-up. The women completed the Cervantes Scale (CS), Hospital Anxiety and Depression Scale (HADS) and Health Assessment Questionnaire (HAQ). The CRF was determined from the Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F). The serum 25(OH)D was determined by electrochemiluminescence, with cut-off point above 75 nmol/L adopted as sufficiency. Generalized Linear Model (GLzM) and Generalized Mixed Model (GMM) analysis were used.

Results

At baseline, 36% (n = 32) of the women presented CRF and 39.3% (n = 35) had 25(OH)D below 75 nmol/L. None of the women reached the Estimated Average Requirements (EAR) of vitamin D. The causality between 25(OH)D and CRF was not significant. Longitudinally, lower levels of 25(OH)D had a negative effect on anxiety (p = 0.020), Menopause and Health (p = 0.033) and Vasomotor scores (p = 0.007). Also, the CRF had a negative effect on anxiety (p = 0.028); depression (p = 0.027); functional disability (p = 0.022); HRQL (p = 0.007); Menopause and Health (p = 0.042), Psychological (p = 0.008) and Couple Relations (p = 0.008) domains; and on Health (p = 0.019) and Aging (p = 0.036) subdomains. Vasomotor subdomain (β = -2.279,p = 0.045) and muscle/joint aches (β = -0.779,p = 0.013) were significant with CRF only at baseline.

Conclusions

This study found negative effect of body adiposity on CRF. Still, the clinical relevance of 25(OH)D and CRF is highlighted, especially that of CRF, considering the consistent impact on several adverse effects reported by BC survivors during adjuvant endocrine therapy.
Knowledge and practice of pediatricians regarding childhood constipation in the Arab world: results from a multicenter survey
Authors: Hasosah Mohammed , Haleem Azad , Jacobson Kevan , Alshemmeri Bassel , Alenazi Aziz , Badei Ahmed Abdel , Massoud Peggy
Published: August 2022

Objectives

We aimed to evaluate knowledge and practice styles among medical providers with different professions and working in different Arab countries regarding their approach to childhood constipation.

Methods

We conducted a cross-sectional multinational survey in eight Arab countries. Pediatric care providers (PCPs), including pediatric specialists (PSs), pediatric residents (PRs), pediatric consultants (PCs), pediatric gastroenterologists (PGs), general practitioners (GPs), and pediatric surgeons (PSu), were included in our study. The survey was anonymous, and participants provided input on the definition and management of constipation.

Results

Of 4000 PCPs, 2579 completed the survey (response rate of 64.5%). Although the majority of respondents were aware of the Rome IV criteria to diagnose constipation, significant differences in the percentage of participants in different geographic countries regarding the definition of constipation were noted. Polyethylene glycol (PEG) was prescribed as a first-line treatment of fecal disimpaction significantly more frequently by pediatricians (PSs, PRs, PCs, PGs) than GPs and PSu (12.8% versus 7.2%, respectively; p < 0.001). Additionally, we found that pediatricians used special milk (high magnesium) as a first-choice formula significantly more often than other physicians (53.7% versus 37%, P < 0.001). For maintenance therapy, both pediatricians and nonpediatricians used dietary management with a special milk formula more than other treatment options (84.2% and 84%, respectively).

Conclusions

Despite increased awareness of the Rome IV criteria, significant differences in knowledge and practice patterns regarding fecal disimpaction exist among PCPs from different Arab countries. The identification of these gaps may be helpful for policy-makers to produce targeted instructional resources on constipation for PCPs.
Depression and its associated factors among primary caregivers of adult cancer patients at Northwest Amhara Regional States Referrals Hospitals oncology treatment units, Northwest Ethiopia, 2021
Authors: Wassie Likinaw Abebaw , Azagew Abere Woretaw , Bifftu Berhanu Boru
Published: August 2022

Introduction

Cancer is a primary and challenging health problem, has a significant impact on caregivers, and is a leading cause of emotional responses like depression. Depression is the most common and serious psychiatric disorder that has a considerable effect on the daily life of primary caregivers. Different articles reported that the magnitude of depression was prevalent among primary caregivers of patients with cancer. There is scarcity of published articles about the problem in Ethiopia. This study aimed to assess the prevalence of depression and associated factors among primary caregivers of adult cancer patients at Northwest Amhara Regional States Referrals Hospitals, oncology treatment units, Northwest Ethiopia, 2021.

Methods

An institutional-based cross-sectional study was conducted in Northwest Amhara Regional States Referrals Hospitals. A systematic random sampling technique was used to select 421 participants. The data were collected using interviewer-administered and chart review through structured, pretested Patient Health Questionarie-9 questionnaires. The data were entered into Epi. Data version 4.6 and analyzed using Stata version 14.0. Bivariable and multivariable logistic regression were carried out to identify factors associated with depression. Adjusted odds ratio with a 95% confidence interval and variables with a p-value < 0.05 were considered significantly associated with depression.

Results

The prevalence of depression was 45.15%. Being female (AOR = 2.01, 95%, CI: 1.27–3.19), having an average monthly income of < 1000 Ethiopian birr (AOR = 3.54, 95% CI: 1.54–8.13), and primary caregivers of a cancer patient with mixed therapy (AOR = 4.54, 95%, CI: (1.5–13.48) were significantly associated with depression.

Conclusion

The prevalence of depression among primary caregivers of adult patients with cancer was significant. It’s better, health care providers in oncology treatment facilities need to recognize and screen and give special attention to female primary caregivers, having an average monthly income of < 1000 Ethiopian birr, and primary caregivers of a cancer patient with mixed therapy to reduce the risk of developing depression.
Estimating the lagged effect of price discounting: a time-series study on sugar sweetened beverage purchasing in a supermarket
Authors: Mamiya Hiroshi , Schmidt Alexandra M. , Moodie Erica E. M. , Buckeridge David L.
Published: August 2022

Background

Price discount is an unregulated obesogenic environmental risk factor for the purchasing of unhealthy food, including Sugar Sweetened Beverages (SSB). Sales of price discounted food items are known to increase during the period of discounting. However, the presence and extent of the lagged effect of discounting, a sustained level of sales after discounting ends, is previously unaccounted for. We investigated the presence of the lagged effect of discounting on the sales of five SSB categories, which are soda, fruit juice, sport and energy drink, sugar-sweetened coffee and tea, and sugar-sweetened drinkable yogurt.

Methods

We fitted distributed lag models to weekly volume-standardized sales and percent discounting generated by a supermarket in Montreal, Canada between January 2008 and December 2013, inclusive (n = 311 weeks).

Results

While the sales of SSB increased during the period of discounting, there was no evidence of a prominent lagged effect of discounting in four of the five SSB; the exception was sports and energy drinks, where a posterior mean of 28,459 servings (95% credible interval: 2661 to 67,253) of excess sales can be attributed to thelaggedeffect in the target store during the 6 years study period.

Conclusion

Our results indicate that studies that do not account for the lagged effect of promotions may not fully capture the effect of price discounting for some food categories.
Absence of a weekday effect on short- and long-term oncologic outcomes of gastrectomy for gastric cancer: a propensity score matching analysis
Authors: Uchida Tsuneyuki , Sekine Ryuichi , Matsuo Kenichi , Kigawa Gaku , Umemoto Takahiro , Makuuchi Mikio , Tanaka Kuniya
Published: August 2022

Background

Day of the week when elective gastrointestinal surgery is performed may be influenced by various background and tumor-related factors. Relationships between postoperative outcome and when in the week gastrectomy is performed remain controversial. We undertook this study to evaluate whether weekday of gastrectomy influenced outcomes of gastric cancer treatment (“weekday effect”).

Methods

Patients who underwent curative surgery for gastric cancer between 2004 and 2017 were included in this retrospective study. To obtain 2 cohorts well balanced for variables that might influence clinical outcomes, patients whose gastrectomy was performed early in the week (EW group) were matched 1:1 with others undergoing gastrectomy later in the week (LW group) by use of propensity scores.

Results

Among 554 patients, 216 were selected from each group by propensity score matching. Incidence of postoperative complications classified as Clavien-Dindo grade II or higher was similar between EW and LW groups (20.4% vs. 24.1%; P = 0.418). Five-year overall and recurrence-free survival were 86.0% and 81.9% in the EW group, and 86.2% and 81.1% in the LW group (P = 0.981 and P = 0.835, respectively).

Conclusions

Short- and long-term outcomes were comparable between gastric cancer patients who underwent gastrectomy early and late in the week.
Network pharmacology and molecular docking technology-based predictive study of the active ingredients and potential targets of rhubarb for the treatment of diabetic nephropathy
Authors: Fu Shaojie , Zhou Yena , Hu Cong , Xu Zhonggao , Hou Jie
Published: August 2022

Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the main cause of end-stage renal failure. Rhubarb is a widely used traditional Chinese herb, and it has exhibited efficacy in reducing proteinuria, lowering blood sugar levels and improving kidney function in patients with DN. However, the exact pharmacological mechanism by rhubarb improves DN remain unclear due to the complexity of its ingredients. Hence, we systematically explored the underlying mechanisms of rhubarb in the treatment of DN. We adopted a network pharmacology approach, focusing on the identification of active ingredients, drug target prediction, gene collection, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment. Molecular docking technology was used to verify the binding ability between the main active compounds and central therapeutic targets, and screen out the core active ingredients in rhubarb for the treatment of DN. Finally, molecular dynamics simulation was performed for the optimal core protein-ligand obtained by molecular docking using GROMACS software. The network analysis identified 16 active compounds in rhubarb that were linked to 37 possible therapeutic targets related to DN. Through protein–protein interaction analysis, TP53, CASP8, CASP3, MYC, JUN and PTGS2 were identified as the key therapeutic targets. By validation of molecular docking, finding that the central therapeutic targets have good affinities with the main active compounds of rhubarb, and rhein, beta-sitosterol and aloe-emodin were identified as the core active ingredients in rhubarb for the treatment of DN. Results from molecular dynamics simulations showed that TP53 and aloe-emodin bound very stably with a binding free energy of − 26.98 kcal/mol between the two. The results of the gene enrichment analysis revealed that the PI3K-Akt signalling pathway, p53 signalling pathway, AGE-RAGE signalling pathway and MAPK signalling pathway might be the key pathways for the treatment of DN, and these pathways were involved in podocyte apoptosis, glomerular mesangial cell proliferation, inflammation and renal fibrosis. Based on the network pharmacology approach and molecular docking technology, we successfully predicted the active compounds and their respective targets. In addition, we illustrated the molecular mechanisms that mediate the therapeutic effects of rhubarb against DN. These findings provided an important scientific basis for further research of the mechanism of rhubarb in the treatment of DN.
A qualitative reflexive thematic analysis into the experiences of being identified with a BRCA1/2 gene alteration: “So many little, little traumas could have been avoided”
Authors: Warner Nikolett Zsuzsanna , Groarke AnnMarie
Published: August 2022

Background

BRCA1/2 alterations increase females’ lifetime breast cancer risk to 40 – 90%, ovarian cancer to 10 – 60%, and males’ lifetime prostate cancer risk to ~ 10 – 25%. Psychosocial issues such as heightened distress can, therefore, occur in this population. This study aimed to explore the subjective experiences and needs of theBRCA1/2 alteration population in navigating cancer risk reduction measures.

Method

This study aimed to explore the experiences and identify the needs of 18BRCA1/2 alteration carriers, recruited through strategic sampling. A public and patient panel (N = 6) collaborated on study development. Data were analysed using reflexive thematic analysis.

Results

Two themes were identified: (i) Healthcare Services as a Burden to Navigate, and (ii) Burden Experienced Through Interactions with Healthcare Professionals. Results indicated uncertainty regarding care pathways, alongside a lack of relevant information. Participants felt unsupported by healthcare professionals, and as though healthcare professionals often perceive them as a burden.

Conclusions

These findings suggest that the quality of interactions in healthcare systems are of relevance to theBRCA1/2 alteration population, and that uncertainty surrounding access to services and information is prevalent. The establishment of specialist hereditary cancer clinics could reduce such burden.
Task sharing in an interprofessional medication management program – a survey of general practitioners and community pharmacists
Authors: Moecker Robert , Weissenborn Marina , Klingenberg Anja , Wirbka Lucas , Fuchs Andreas , Eickhoff Christiane , Mueller Uta , Schulz Martin , Kaufmann-Kolle Petra ,   ARMIN Study Group, Auerbach Anja , Braun Dorit , Doehler Catharina , Donner Susanne , Fink Stefan , Frasch Jona , Honscha Christine , Kuhn Urs Dieter , Maetzler Mike , Maywald Ulf , Meid Andreas D. , Moeckel Anke , Ruff Carmen , Stoll Felicitas , Wagner Kathrin , Haefeli Walter E. , Seidling Hanna M.
Published: August 2022

Background

Pharmacist-led medication review and medication management programs (MMP) are well-known strategies to improve medication safety and effectiveness. If performed interprofessionally, outcomes might even improve. However, little is known about task sharing in interprofessional MMP, in which general practitioners (GPs) and community pharmacists (CPs) collaboratively perform medication reviews and continuously follow-up on patients with designated medical and pharmaceutical tasks, respectively. In 2016, ARMIN (Arzneimittelinitiative Sachsen-Thüringen) an interprofessional MMP was launched in two German federal states, Saxony and Thuringia. The aim of this study was to understand how GPs and CPs share tasks in MMP when reviewing the patients’ medication.

Methods

This was a cross-sectional postal survey among GPs and CPs who participated in the MMP. Participants were asked who completed which MMP tasks, e.g., checking drug-drug interactions, dosing, and side effects. In total, 15 MMP tasks were surveyed using a 5-point Likert scale ranging from “I complete this task alone” to “GP/CP completes this task alone”. The study was conducted between 11/2020 and 04/2021. Data was analyzed using descriptive statistics.

Results

In total, 114/165 (69.1%) GPs and 166/243 (68.3%) CPs returned a questionnaire. The majority of GPs and CPs reported (i) checking clinical parameters and medication overuse and underuse to be completed by GPs, (ii) checking storage conditions of drugs and initial compilation of the patient’s medication including brown bag review being mostly performed by CPs, and (iii) checking side-effects, non-adherence, and continuous updating of the medication list were carried out jointly. The responses differed most for problems with self-medication and adding and removing over-the-counter medicines from the medication list. In addition, the responses revealed that some MMP tasks were not sufficiently performed by either GPs or CPs.

Conclusions

Both GPs’ and CPs’ expertise are needed to perform MMP as comprehensively as possible. Future studies should explore how GPs and CPs can complement each other in MMP most efficiently.
Downregulated TICAM1 is a prognostic biomarker and associated with immune tolerance of Wilms tumor patients
Authors: Lu Zhiyi , Sun Fengyin
Published: August 2022

Background

TIR domain containing adaptor molecule 1 (TICAM1) is a coding gene participating in immune and inflammation responses to malignant cells. However, the role of TICAM1 in Wilms tumor (WT) is rarely known.

Materials and methods

The expression level of TICAM1 was calculated in the WT TARGET cohort and validated using the GSE66405 cohort. The Kaplan–Meier method was employed to investigate the potential clinical value of TICAM1 and the association between its expression level and clinical features. The influence of TICAM1 on immune infiltration was examined by ESTIMATE, CIBERSORT and MCPcounter algorithms. IC50 of chemotherapeutic drugs was calculated by “pRRophetic” R package.

Results

TICAM1 was downregulated in WT patients with worse prognosis and a more advanced clinical stage. Moreover, a low expression level of TICAM1 contributed to less immune cell infiltration, few protective immune cells and more antitumor immune cells.

Conclusions

TICAM1 exerts a significant impact on the prognosis, progression and immune infiltration condition of WT.
Evolocumab on top of empagliflozin improves endothelial function of individuals with diabetes: randomized active-controlled trial
Authors: Sposito Andrei C. , Breder Ikaro , Barreto Joaquim , Breder Jessica , Bonilha Isabella , Lima Marcus , Oliveira Alessandra , Wolf Vaneza , Luchiari Beatriz , do Carmo Helison R. , Munhoz Daniel , Oliveira Daniela , Coelho-Filho Otavio R. , Coelho Otavio R. , Matos-Souza Jose Roberto , Moura Filipe A. , de Carvalho Luiz Sergio F. , Nadruz Wilson , Quinaglia Thiago , Kimura-Medorima Sheila T. ,   the EXCEED-BHS3 Group
Published: August 2022

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known.

Objectives

To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i.

Methods

Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane.

Results

A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [−1.7 (5.9) vs. −1.1 (5.3); p < 0.001).

Conclusions

In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.