bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of serum creatinine with aortic arch calcification in middle-aged and elderly adults: an observational cross-sectional study from China
Authors: Zhang Feifei , Hao Nannan , Wang Lei , Sun Guoming , Feng Xiaoke , Li Chunjian , Tan Wenfeng , Wang Fang
Published: April 2022

Background and aims

Vascular calcification (VC) is a strong predictor of cardiovascular events and all-cause mortality in cardiovascular diseases (CVD). Renal dysfunction is closely related to VC. Serum creatinine, as an important indicator of renal function in chronic kidney disease (CKD), is closely associated with increased VC. Here, to explore the potential role of serum creatinine in CVD, we examined the association between serum creatinine level and aortic arch calcification (AAC) presence in a larger general population.

Methods

A total of 9067 participants aged > 45 years were included in this study. All participants underwent postero-anterior chest X-ray examination to diagnose AAC. According to the distribution characteristics, serum creatinine levels in male and female were divided into tertiles respectively. Univariate and multivariate logistic regression analysis were used to analyze the association between aortic calcification and serum creatinine.

Results

Participants included 3776 men and 5291 women, and 611 and 990 AAC were detected, respectively. Serum creatinine level in the female AAC group was significantly higher than that in the non-AAC group (p < 0.001), while there was no significant difference in male serum creatinine between the two groups (p = 0.241). After logistic regression analysis excluded confounding factors, with the first tertile of serum creatinine as the reference, multivariable-adjusted ORs and 95% CIs of the second and the highest tertile of female and male were 1.045 (0.856–1.276), 1.263 (1.036–1.539); 0.953 (0.761–1.193), 0.948 (0.741–1.198), respectively.

Conclusion

Elevated serum creatinine levels are independently associated with higher AAC incidence in female aged > 45 years old. Measuring serum creatinine levels may assist the early screening individuals at high risk of developing CVD. And higher attention should be given to female's serum creatinine levels in daily clinical practice.
Clinical factors associated with recent medical care visits in nursing homes: a multi-site cross-sectional study
Authors: Correia Rebecca H. , Mowbray Fabrice I. , Dash Darly , Katz Paul R. , Moser Andrea , Strum Ryan P. , Jones Aaron , von Schlegell Ahmad , Costa Andrew P.
Published: April 2022

Objectives

We examined which resident-level clinical factors influence the provision of a recent medical care visit in nursing homes (NHs).

Design

Multi-site cross-sectional.

Setting and participants

We extracted data on 3,556 NH residents from 18 NH facilities in Ontario, Canada, who received at minimum, an admission and first-quarterly assessment with the Resident Assessment Instrument Minimum Data Set (MDS) 2.0 between November 1, 2009, and October 31, 2017.

Methods

We conducted a secondary analysis of routinely collected MDS 2.0 data. The provision of a recent medical care visit by a physician (or authorized clinician) was assessed in the 14-day period preceding a resident’s first-quarterly MDS 2.0 assessment. We utilized best-subset multivariable logistic regression to model the adjusted associations between resident-level clinical factors and a recent medical care visit.

Results

Two thousand eight hundred fifty nine (80.4%) NH residents had one or more medical care visits prior to their first-quarterly MDS 2.0 assessment. Six clinically relevant factors were identified to be associated with recent medical care visits in the final model: exhibiting wandering behaviours (OR = 1.34, 95% CI 1.09 – 1.63), presence of a pressure ulcer (OR = 1.37, 95% CI 1.05 – 1.78), a urinary tract infection (UTI) (OR = 1.52, 95% CI 1.06 – 2.18), end-stage disease (OR = 9.70, 95% CI 1.32 – 71.02), new medication use (OR = 1.31, 95% CI 1.09 – 1.57), and analgesic use (OR = 1.24, 95% CI 1.03 – 1.49).

Conclusions and implications

Our findings suggest that resident-level clinical factors drive the provision of medical care visits following NH admission. Clinical factors associated with medical care visits align with the minimum competencies expected of physicians in NH practice, including managing safety risks, infections, medications, and death. Ensuring that NH physicians have opportunities to acquire and strengthen these competencies may be transformative to meet the ongoing needs of NH residents.
A novel technique using ultrasonography in upper airway management after anterior cervical decompression and fusion
Authors: Murata Shizumasa , Iwasaki Hiroshi , Oka Hiroyuki , Hashizume Hiroshi , Yukawa Yasutsugu , Minamide Akihito , Tsutsui Shunji , Takami Masanari , Nagata Keiji , Taiji Ryo , Kozaki Takuhei , Yamada Hiroshi
Published: April 2022

Background

Airway complications are the most serious complications after anterior cervical decompression and fusion (ACDF) and can have devastating consequences if their detection and intervention are delayed. Plain radiography is useful for predicting the risk of dyspnea by permitting the comparison of the prevertebral soft tissue (PST) thickness before and after surgery. However, it entails frequent radiation exposure and is inconvenient. Therefore, we aimed to overcome these problems by using ultrasonography to evaluate the PST and upper airway after ACDF and investigate the compatibility between X-ray and ultrasonography for PST evaluation.

Methods

We included 11 radiculopathy/myelopathy patients who underwent ACDF involving C5/6, C6/7, or both segments. The condition of the PST and upper airway was evaluated over 14 days. The Bland–Altman method was used to evaluate the degree of agreement between the PST values obtained using radiography versus ultrasonography. The Pearson correlation coefficient was used to determine the relationship between the PST measurement methods. Single-level and double-level ACDF were performed in 8 and 3 cases, respectively.

Results

PST and upper airway thickness peaked on postoperative day 3, with no airway complications. The Bland–Altman bias was within the prespecified clinically nonsignificant range: 0.13 ± 0.36 mm (95% confidence interval 0.04–0.22 mm). Ultrasonography effectively captured post-ACDF changes in the PST and upper airway thickness and detected airway edema.

Conclusions

Ultrasonography can help in the continuous assessment of the PST and the upper airway as it is simple and has no risk of radiation exposure risk. Therefore, ultrasonography is more clinically useful to evaluate the PST than radiography from the viewpoint of invasiveness and convenience.
Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer
Authors: ten Hoorn Sanne , Waasdorp Cynthia , van Oijen Martijn G. H. , Damhofer Helene , Trinh Anne , Zhao Lan , Smits Lisanne J. H. , Bootsma Sanne , van Pelt Gabi W. , Mesker Wilma E. , Mol Linda , Goey Kaitlyn K. H. , Koopman Miriam , Medema Jan Paul , Tuynman Jurriaan B. , Zlobec Inti , Punt Cornelis J. A. , Vermeulen Louis , Bijlsma Maarten F.
Published: April 2022

Background

Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC).

Methods

Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20).

Results

ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11–1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06–3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25–3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers.

Conclusions

Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum.
Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review
Authors: Lunardi Mattia , Al-Habbaa Ahmed , Abdelshafy Mahmoud , Davey Matthew G. , Elkoumy Ahmed , Ganly Sandra , Elzomor Hesham , Cawley Christian , Sharif Faisal , Crowley James , Kerin Michael , Wijns William , Lowery Aoife , Soliman Osama
Published: April 2022

Cancer-therapy related cardiotoxicity (CTRCT) is a significant and frequent complication of monoclonal antibody directed therapy, especially Trastuzumab, for human epidermal growth factor receptor 2 (HER2) overexpressing breast cancers. Reliable, clinically available molecular predictive markers of CTRCT have not yet been developed. Identifying specific genetic variants and their molecular markers, which make the host susceptible to this complication is key to personalised risk stratification. A systematic review was conducted until April 2021, using the Medline, Embase databases and Google Scholar, to identify studies genetic and RNA-related markers associated with CTRCT in HER2 positive breast cancer patients. So far, researchers have mainly focused on HER2 related polymorphisms, revealing codons 655 and 1170 variants as the most likely SNPs associated with cardiotoxicity, despite some contradictory results. More recently, new potential genetic markers unrelated to the HER2 gene, and linked to known cardiomyopathy genes or to genes regulating cardiomyocytes apoptosis and metabolism, have been detected. Moreover, microRNAs are gaining increasing recognition as additional potential molecular markers in the cardio-oncology field, supported by encouraging preliminary data about their relationship with cardiotoxicity in breast cancers. In this review, we sought to synthesize evidence for genetic variants and RNA-related molecular markers associated with cardiotoxicity in HER2-positive breast cancer.
Risk factors for cut-outs in geriatric intertrochanteric fractures with cephalomedullary nailing after obtaining acceptable reduction: a case–control study
Authors: Huang Jian-wen , Gao Xiao-sheng , Yang Yun-fa
Published: April 2022

Background

It is irresponsible if we disregard reduction quality to talk about cut-outs in intertrochanteric fractures (ITF) with internal fixation. The aim of this study is to analyze the risk-factors for cut-outs in geriatric ITF with cephalomedullary nailing after obtaining acceptable reduction.

Methods

In order to investigate the risk-factors for cut-outs in geriatric ITF after obtaining acceptable reduction, we retrospectively reviewed 367 patients who underwent cephalomedullary nail for ITF in our department between September 2016 and December 2021. Potential variables including demographic data and radiological parameters (namely the fracture type, Singh index, lateral wall fracture, cephalic nail position, Parker’s ratio index, tip-apex-distance (TAD), and calcar-referenced TAD (CalTAD)) were collected. Logistic regression analysis was performed to identify the significant risk factors for cut-outs.

Results

One hundred twenty-one patients were suitable for this study. Of the 121 cases, nine cases (7.4%) were observed with cut-out or pending cut-out. We found that Age (adjusted odds ratio (OR) 1.158, 95% confidence interval (CI) 1.016 to 1.318, p = 0.028), lateral wall fracture (adjusted OR 11.07, 95%CI 1.790 to 68.380, p = 0.01), and CalTAD (adjusted OR 1.277, 95%CI 1.005 to 1.622, p = 0.045) were independent risk-factors for cut-outs.

Conclusions

Age, lateral wall fracture and CalTAD are independent risk-factors for cut-outs in geriatric ITF with cephalomedullary nailing after obtaining acceptable reduction. In order to avoid cut-outs, an optimal CalTAD is necessary even obtaining acceptable reduction, especially in the over-aged patients with lateral wall fracture.
Human albumin and 6% hydroxyethyl starches (130/0.4) in cardiac surgery: a meta-analysis revisited
Authors: Wiedermann Christian J.
Published: April 2022

Background

A meta-analysis of randomized controlled trials was recently published in BMC Surgery that compared the use of human albumin with 6% hydroxyethyl starches 130/0.4 for cardiopulmonary bypass prime and perioperative fluid management in pediatric and adult cardiac surgery patients. The two plasma expanding solutions are described as equivalent for efficacy and safety outcomes, and, on that basis, the preferential use of hydroxyethyl starches 130/0.4 was recommended for economic reasons because of the higher unit costs of human albumin solutions.

Results

In addition to the fact that trials were mostly small, single-center studies and the number of total participants was low, making the meta-analysis underpowered for several outcomes, selective reporting of data for ICU length of stay was identified. Re-calculation of statistics at higher precision showed that ICU length of stay of patients in the human albumin group was significantly shorter than that of patients in the 6% hydroxyethyl starches 130/0.4 group (standard mean difference − 0.181, 95% confidence interval − 0.361 to − 0.001, P = 0.049), which may offset any proposed economic advantage of using 6% hydroxyethyl starches 130/0.4. At the same time, the renal safety of 6% hydroxyethyl starches 130/0.4 in surgical patients is under regulatory review.

Conclusions

Underpowered trials and selective reporting may impair the validity of the meta-analysis. A more cautious conclusion about the interchangeability between human albumin and 6% hydroxyethyl starches 130/0.4 in cardiac surgery should have been reached.
A clinical observational study of effectiveness of a solid coupling medium in extracorporeal shock wave lithotripsy
Authors: Chang Hao-Han , Lin Yu-Chih , Li Ching-Chia , Wu Wen-Jeng , Liou Wen-Chin , Lin Yusen Eason , Huang Kuo-Kuang , Chen Wei-Chuan
Published: April 2022

This study aimed to investigate clinical effectiveness of stone disintegration by using isolation coupling pad (“icPad”) as coupling medium to reduce trapped air pockets during extracorporeal shock wave lithotripsy (ESWL). Patients underwent ESWL between Oct. 2017 and May 2018 were enrolled in this clinical observational study. An electromagnetic lithotripter (Dornier MedTech Europe GmbH Co., Germany) was used in this study. Patients were divided into icPad group P1, P2 and semi-gel group C by different coupling medium. The energy level and total number of shock wave (SW) for group P1 and C was set at level 2 and 3000 and group P2 at level 3 and 2500. The successful stone disintegration rate (SSDR) was determined to evaluate the treatment outcome. All patients were evaluated by KUB film and ultrasonography after 90 days. Complications during ESWL were recorded. A total of 300 patients satisfied the inclusion criteria. There were no significant differences in characteristics of patients and stone among three groups. The corresponding SSDRs for patients in group P1, P2 and C was 73.0%, 73.2% and 55.3%, respectively. The SSDR in group P1 was statistically higher than Group C. Comparing to semi-liquid gel, coupling medium using by icPad could achieve better treatment outcome of stone disintegration in ESWL.
Different expression patterns of inflammatory cytokines induced by lipopolysaccharides from Escherichia coli or Porphyromonas gingivalis in human dental pulp stem cells
Authors: Lan Chunhua , Chen Shuai , Jiang Shan , Lei Huaxiang , Cai Zhiyu , Huang Xiaojing
Published: April 2022

Background

Lipopolysaccharide (LPS) is one of the leading causes of pulpitis. The differences in establishing an in vitro pulpitis model by using different lipopolysaccharides (LPSs) are unknown. This study aimed to determine the discrepancy in the ability to induce the expression of inflammatory cytokines and the underlying mechanism betweenEscherichia coli(E. coli) andPorphyromonas gingivalis(P. gingivalis) LPSs in human dental pulp stem cells (hDPSCs).

Material and methods

Quantitative real-time polymerase chain reaction (QRT-PCR) was used to evaluate the mRNA levels of inflammatory cytokines including IL-6, IL-8, COX-2, IL-1β, and TNF-α expressed by hDPSCs at each time point. ELISA was used to assess the interleukin-6 (IL-6) protein level. The role of toll-like receptors (TLR)2 and TLR4 in the inflammatory response in hDPSCs initiated by LPSs was assessed by QRT-PCR and flow cytometry.

Results

TheE. coliLPS significantly enhanced the mRNA expression of inflammatory cytokines and the production of the IL-6 protein (p < 0.05) in hDPSCs. The peaks of all observed inflammation mediators’ expression in hDPSCs were reached 3–12 h after stimulation by 1 μg/mLE. coliLPS.E. coliLPS enhanced the TLR4 expression (p < 0.05) but not TLR2 in hDPSCs, whereasP. gingivalisLPS did not affect TLR2 or TLR4 expression in hDPSCs. The TLR4 inhibitor pretreatment significantly inhibited the gene expression of inflammatory cytokines upregulated byE. coliLPS (p < 0.05).

Conclusion

Under the condition of this study,E. coliLPS but notP. gingivalisLPS is effective in promoting the expression of inflammatory cytokines by hDPSCs.E. coliLPS increases the TLR4 expression in hDPSCs.P. gingivalisLPS has no effect on TLR2 or TLR4 expression in hDPSCs.
Palliative radiotherapy for gastric cancer bleeding: a multi-institutional retrospective study
Authors: Takeda Kazuya , Sakayauchi Toru , Kubozono Masaki , Katagiri Yu , Umezawa Rei , Yamamoto Takaya , Ishikawa Yojiro , Takahashi Noriyoshi , Suzuki Yu , Kishida Keita , Jingu Keiichi
Published: April 2022

Background

Palliative radiotherapy for gastric cancer bleeding has been reported to be a safe and effective treatment, but predictive factors for achievement of hemostasis and overall survival have not been established.

Methods

In this retrospective study, 120 courses of palliative radiotherapy for gastric cancer bleeding in 117 patients in 4 institutes in Japan were reviewed with approval of the ethical committee in each institute. The rate of achieving hemostasis was evaluated by 50% or more reduction of red blood cell transfusion before and after the start of radiotherapy, elevation of blood hemoglobin concentration in a period of 4 weeks from the start of radiotherapy or improvement of subjective or objective clinical symptoms in a period of 4 weeks from the start of radiotherapy. Predictive factors for overall survival and achieving hemostasis were investigated with the Cox hazards model.

Results

The median overall survival period was 3.7 months. Multivariate analysis showed that absence of metastatic disease, higher biological effective dose, higher serum albumin level, lower blood urea nitrogen level and lower neutrophil-to-lymphocyte ratio (NLR) were associated with longer overall survival. Elevation of hemoglobin concentration in a period of 4 weeks from the start of radiotherapy (mean concentration: 8.2 g/dL vs. 8.9 g/dL, p = 0.006) and decrease in the amount of red cell transfusion from a 4-week period before to a 4-week period after the start of radiotherapy (mean amount: 716 mL vs. 230 mL, p < 0.0001) were observed. The overall rate of achievement of hemostasis was 59.6%. In multivariate analysis, higher biological effective dose was associated with achievement of hemostasis. Grade 2 or higher acute adverse effects related to radiotherapy were observed in 17.5% of cases in 120 treatment courses. Six cases (5.0%) had grade 3 or 4 adverse effects including gastric penetration in 1 patient and anorexia requiring total parental nutrition in 3 patients. No grade 5 adverse effects were observed.

Conclusions

Palliative radiotherapy for gastric cancer bleeding seems to be an effective and safe treatment strategy. Higher treatment dose was associated with longer overall survival and a hemostatic effect. Some hematological parameters may predict overall survival, and they would be helpful for deciding the treatment strategy.
Multimorbidity among midlife women in India: well-being beyond reproductive age
Authors: Puri Parul , Sinha Abhinav , Mahapatra Pranab , Pati Sanghamitra
Published: April 2022

Background

Currently, inequality in life expectancy across gender makes women outlive men. Adult women transit towards menopause around midlife accompanied by a series of natural physiological changes leading to several conditions such as osteoporosis, depression, and urinary incontinence, which puts them at a higher risk of having multimorbidity. Multimorbidity is often associated with poorer quality of life, leading to deteriorated work productivity and associated economic loss in midlife. Hence, this study aimed to determine the magnitude and correlates of early onset of multimorbidity and explore its linkages with health-related quality of life (HRQoL) among middle-aged women in India.

Methods

We have utilized data from the first round of the Longitudinal Ageing Study in India, 2017–19. We included women aged 45–65 years (n = 23,951) for analysis. Descriptive data were presented. An ordered logistic regression was conducted and proportional odds were reported to identify the correlates of multimorbidity. To explore the linkages between multimorbidity and selected indicators of HRQoL, an array of regression models were executed.

Results

Multimorbidity was reported amongst 29.8% of women in midlife. Chandigarh (PR-54.8 PER 100 women) and Punjab (PR-52.8 per 100 women) reported the highest prevalence of multimorbidity. Women with multimorbidity reported compromised HRQoL indicators such as self-rated health, work-limiting health conditions, mobility, and activities of daily living.

Conclusions

Multimorbidity is increasingly prevalent in midlife women associated with inferior quality of life. The reproductive health programs for women should consist of midlife women focusing on multimorbidity and overall well-being.
Operational definition of complementary, alternative, and integrative medicine derived from a systematic search
Authors: Ng Jeremy Y. , Dhawan Tushar , Dogadova Ekaterina , Taghi-Zada Zhala , Vacca Alexandra , Wieland L. Susan , Moher David
Published: April 2022

Background

Identifying what therapies constitute complementary, alternative, and/or integrative medicine (CAIM) is complex for a multitude of reasons. An operational definition is dynamic, and changes based on both historical time period and geographical location whereby many jurisdictions may integrate or consider their traditional system(s) of medicine as conventional care. To date, only one operational definition of “complementary and alternative medicine” has been proposed, by Cochrane researchers in 2011. This definition is not only over a decade old but also did not use systematic methods to compile the therapies. Furthermore, it did not capture the concept “integrative medicine”, which is an increasingly popular aspect of the use of complementary therapies in practice. An updated operational definition reflective of CAIM is warranted given the rapidly increasing body of CAIM research literature published each year.

Methods

Four peer-reviewed or otherwise quality-assessed information resource types were used to inform the development of the operational definition: peer-reviewed articles resulting from searches across seven academic databases (MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, Scopus and Web of Science); the “aims and scope” webpages of peer-reviewed CAIM journals; CAIM entries found in online encyclopedias, and highly-ranked websites identified through searches of CAIM-related terms on HONcode. Screening of eligible resources, and data extraction of CAIM therapies across them, were each conducted independently and in duplicate. CAIM therapies across eligible sources were deduplicated.

Results

A total of 101 eligible resources were identified: peer-reviewed articles (n = 19), journal “aims and scope” webpages (n = 22), encyclopedia entries (n = 11), and HONcode-searched websites (n = 49). Six hundred four unique CAIM terms were included in this operational definition.

Conclusions

This updated operational definition is the first to be informed by systematic methods, and could support the harmonization of CAIM-related research through the provision of a standard of classification, as well as support improved collaboration between different research groups.
Uncovering the potential mechanism of Xue Fu Zhu Yu Decoction in the treatment of intracerebral hemorrhage
Authors: Xue Dao-jin , Zhen Zheng , Wang Ke-xin , Zhao Jia-lin , Gao Yao , Chen Yu-peng , Shen You-bi , Peng Zi-zhuang , Guan Dao-gang , Huang Tao
Published: April 2022

Background

Chinese herbal medicine (CHM) is characterized by “multi- compounds, multi-targets and multi-pathway”, which has advanced benefits for preventing and treating complex diseases, but there still exists unsolved issues, mainly include unclear material basis and underlying mechanism of prescription. Integrated pharmacology is a hot cross research area based on system biology, mathematics and poly-pharmacology. It can systematically and comprehensively investigate the therapeutic reaction of compounds or drugs on pathogenic genes network, and is especially suitable for the study of complex CHM systems. Intracerebral Hemorrhage (ICH) is one of the main causes of death among Chinese residents, which is characterized with high mortality and high disability rate. In recent years, the treatment of ICH by CHM has been deeply researched. Xue Fu Zhu Yu Decoction (XFZYD), one of the commonly used prescriptions in treating ICH at clinic level, has not been clear about its mechanism.

Methods

Here, we established a strategy, which based on compounds-targets, pathogenetic genes, network analysis and node importance calculation. Using this strategy, the core compounds group (CCG) of XFZYD was predicted and validated by in vitro experiments. The molecular mechanism of XFZYD in treating ICH was deduced based on CCG and their targets.

Results

The results show that the CCG with 43 compounds predicted by this model is highly consistent with the corresponding Compound-Target (C-T) network in terms of gene coverage, enriched pathway coverage and accumulated contribution of key nodes at 89.49%, 88.72% and 90.11%, respectively, which confirmed the reliability and accuracy of the effective compound group optimization and mechanism speculation strategy proposed by us.

Conclusions

Our strategy of optimizing the effective compound groups and inferring the mechanism provides a strategic reference for explaining the optimization and inferring the molecular mechanism of prescriptions in treating complex diseases of CHM.
Impact of insecticide-treated nets and indoor residual spraying on self-reported malaria prevalence among women of reproductive age in Ghana: implication for malaria control and elimination
Authors: Alhassan Yakubu , Dwomoh Duah , Amuasi Susan Ama , Nonvignon Justice , Bonful Harriet , Tetteh Mary , Agyabeng Kofi , Kotey Martha , Yawson Alfred E. , Bosomprah Samuel
Published: April 2022

Background

The Global Fund alone contributed 56% of all international financing for malaria and has invested more than US$13.5 billion in malaria treatment, prevention, and control programmes by June 2021. These investments include interventions such as mosquito nets, indoor residual spraying, and preventive treatment for children and pregnant women. However, there is paucity of studies for assessment of such investments to a reduction in malaria prevalence. This study was aimed at quantifying the impact of household access to insecticide-treated nets (ITNs) and the indoor residual spraying (IRS) on self-reported malaria prevalence among women of reproductive age in Ghana.

Methods

The study analysed the 2016 Ghana Malaria Indicator Survey (MIS) data. The MIS is a nationwide survey that included women aged 15–49 years. Poisson regression model with inverse probability to treatment weighting was used to determine average treatment effect estimate of the two malaria interventions on self-reported malaria prevalence among women of reproductive age in Ghana.

Results

A total sample of 4861 women interviewed from the 2016 Ghana MIS was used for analysis. The prevalence of self-reported malaria in 2016 was 34.4% (95% CI [32.4%, 36.4%]). Approximately 80.0% of women lived in households with access to ITNs [Percentage (Pr) = 79.9%, (95% CI [78.0%, 81.7%])], 12.4% (95% CI [7.5%, 19.8%]) of the households had access to IRS and 11.4% (95% CI [7.0%, 18.0%]) of the households had access to both ITNs and IRS. Household access to only ITN contributed to 7.1 percentage point (pt) reduction in the self-reported malaria among women (95% CI [− 12.0%, − 2.1%], p = 0.005) whilst IRS at the households contributed to 6.8pt reduction in malaria prevalence (95% CI [− 12.0%, − 2.1%], p = 0.005). Households with access to both ITNs and IRS contributed to a 27.1pt reduction in self-reported malaria prevalence among women (95% CI [− 12.0%, − 2.1%], p = 0.005).

Conclusion

Access to both ITNs and application of IRS at the household level contributed to a significant reduction in self-reported malaria prevalence among women of reproductive age in Ghana. This finding confirms the need for integration of malaria control interventions to facilitate attainment of malaria elimination in Ghana.
I-125 seeds with chemotherapy for progressive non-small-cell lung cancer after first-line treatment: a meta-analysis
Authors: Chen Zhong-Ke , Fan Jing , Li Fen-Qiang , Zhou Shi-Yan , Xu Yuan-Shun
Published: April 2022

Background

Continuing therapy for aggressive non-small-cell lung cancer (NSCLC) after first-line treatment (FLT) is challenging. The clinical efficacy of second-line chemotherapy (SLCT) for progressive NSCLC is limited. In this meta-analysis, we aim to evaluate the clinical efficacy of the combination of I-125 seeds brachytherapy (ISB) and SLCT in progressive NSCLC after FLT.

Methods

The PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases were screened for relevant publications until September 2021. Meta-analyses are conducted by RevMan 5.3 and Stata 12.0.

Results

Our meta-analysis encompassed 6 studies (4 retrospective studies and 2 randomized controlled trials), which included 272 patients that underwent ISB with SLCT (combined group) and 257 patients that received SLCT alone (chemotherapy alone group). The complete response (24.7% vs. 7.0%, P < 0.00001), treatment response (65.7% vs. 38.1%, P = 0.0002), and disease control (95.2% vs. 80.4%, P < 0.00001) rates are markedly elevated for patients receiving combined therapy versus those receiving chemotherapy alone. Moreover, pooled progression-free survival (P = 0.0001) and overall survival (P < 0.00001) were remarkably extended for patients that received the combination therapy, while no obvious differences were detected in the pooled myelosuppression (39.0% vs. 30.6%, P = 0.05) and gastrointestinal response (38.5% vs. 35.9%, P = 0.52) rates between 2 groups. Significant heterogeneity was found in the endpoints of the treatment response and progression-free survival.

Conclusions

This meta-analysis demonstrated that ISB could enhance the clinical efficacy of SLCT in patients with progressive NSCLC after FLT without inducing major toxic side effects.
Flap endonuclease 1 and DNA-PKcs synergistically participate in stabilizing replication fork to encounter replication stress in glioma cells
Authors: Zhang Jing , Chen Mu , Pang Ying , Cheng Meng , Huang Bingsong , Xu Siyi , Liu Min , Lian Hao , Zhong Chunlong
Published: April 2022

Background

Selectively utilizing alternative mechanisms to repair damaged DNA in essential factors deficient cancer facilitates tumor genetic evolution and contributes to treatment resistance. Synthetic lethality strategies provide a novel scenario to anticancer therapy with DNA repair protein mutation, such as glioma with DNA-PKcs-deficiency, a core factor crucial for non-homologous end joining (NHEJ) mediated DNA damage repair. Nevertheless, the clinical significance and molecular mechanisms of synthetic lethality function by interfering tumor DNA replication remain largely unexplored.

Methods

Cancer clinic treatment resistance-related replication core factors were identified through bioinformatics analysis and RNA-sequencing and verified in clinical specimens by immunoblotting and in situ Proximity Ligation Analysis (PLA). Then, in vitro and in vivo experiments, including visible single molecular tracking system were performed to determine functional roles, the molecular mechanisms and clinical significance of synthetic lethality on glioma tumors.

Results

Hyperactive DNA replication and regulator Flap endonuclease 1 (FEN1) provides high efficiency DNA double strand breaks (DSB) repair abilities preventing replication forks collapse during DNA replication which facilitate adaptation to selective pressures. DNA-PKcs deficient glioma cells are highly dependent on FEN1/BRCA1/RAD51 to survival and counteract replication stress. FEN1 protects perturbed forks from erroneous over-resection by MRE11 through regulating of BRCA1-RAD51 and WRN helicase, uncovering an essential genetic interaction between FEN1 and DNA-PKcs in mitigating replication-stress induced tumor genomic instability. Therapeutically, genetic depletion or molecular inhibition of FEN1 and DNA-PKcs perturb glioma progression.

Conclusions

Our findings highlight an unanticipated synthetic interaction between FEN1/BRCA1/RAD51 and DNA-PKcs when dysfunction leads to incompatible with cell survival under conditions of interrupted replication progression by disrupting addictive alternative tumor evolution and demonstrate the applicability of combined FEN1 and DNA-PKcs targeting in the treatment of glioma.
Internet-based cognitive behavioral therapy for improving health-related quality of life in patients with endometriosis: study protocol for a randomized controlled trial
Authors: Schubert Kathrin , Lohse Johanna , Kalder Matthias , Ziller Volker , Weise Cornelia
Published: April 2022

Background

The trial investigates the efficacy of internet-based cognitive behavioral therapy (iCBT) in improving health-related QoL in patients with endometriosis, which is a chronic gynecological condition affecting up to 15% of people with female-assigned reproductive organs. Endometriosis is stress-related and comes with various physical symptoms such as pelvic pain and infertility. It has a substantial impact on health-related quality of life (QoL), and mind-body interventions seem promising in reducing the psychological burden.

Methods

This is a monocentric randomized-controlled trial recruiting 120 patients with endometriosis. The intervention consists of eight iCBT modules focusing on psychoeducation, cognitive restructuring, pacing, and emotion regulation. Participants will receive written feedback from a trained therapist weekly. The comparator is a waitlist control group. All participants will be followed up 3 months after the intervention, and the intervention group will additionally be followed up 12 months after the intervention. Trial participants will not be blinded to the allocated trial arm. Primary outcome measures are endometriosis-related QoL, pain, and pain-related disability. Secondary outcomes include coping, illness representations, and psychological flexibility. Statistical analyses will be performed following intention-to-treat principles.

Discussion

This randomized-controlled trial is the first trial to test the efficacy of iCBT for improving endometriosis-related QoL. Potential predictor variables and key mechanisms in treatment will be investigated to enable further progression in medical and psychological care for patients with endometriosis.

Trial registration

ClinicalTrials.gov, NCT05098444 Registered on October 28, 2021
The effect of a loading dose of meropenem on outcomes of patients with sepsis treated by continuous renal replacement: study protocol for a randomized controlled trial
Authors: Ni Sui-Qing , Teng Wen-Bing , Fu Yong-Hong , Su Wei , Yang Zhi , Cai Jie , Xu Jin-Nuo , Deng Xiao-Ying , Liu Xiang-Fang , Fu Sheng-Nan , Zeng Jun , Zhang Chen
Published: April 2022

Background

Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT.

Methods

This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People’s Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety.

Discussion

This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT.

Trial registration

Chinese Clinical Trials Registry,ChiCTR2000032865. Registered on 13 May 2020,http://www.chictr.org.cn/showproj.aspx?proj=53616.
Ad libitum consumption of protein- or peptide-sucrose solutions stimulates egg formation by prolonging the vitellogenic phase of oogenesis in anautogenous mosquitoes
Authors: Harrison Ruby E. , Chen Kangkang , South Lilith , Lorenzi Ange , Brown Mark R. , Strand Michael R.
Published: April 2022

Background

Anautogenous mosquitoes commonly consume nectars and other solutions containing sugar but are thought to only produce eggs in discrete gonadotrophic cycles after blood-feeding on a vertebrate host. However, some anautogenous species are known to produce eggs if amino acids in the form of protein are added to a sugar solution. Unclear is how different sources of amino acids in sugar solutions affect the processes that regulate egg formation and whether responses vary among species. In this study, we addressed these questions by focusing onAedes aegyptiand conducting some comparative assays withAedes albopictus, Anopheles gambiae, Anopheles stephensiandCulex quinquefasciatus.

Methods

Adult female mosquitoes were fed sugar solutions containing amino acids, peptides or protein. Markers for activation of a gonadotrophic cycle including yolk deposition into oocytes, oviposition, ovary ecdysteroidogenesis, expression of juvenile hormone and 20-hydroxyecdysone-responsive genes, and adult blood-feeding behavior were then measured.

Results

The five anautogenous species we studied produced eggs when fed two proteins (bovine serum albumin, hemoglobin) or a mixture of peptides (tryptone) in 10% sucrose but deposited only small amounts of yolk into oocytes when fed amino acids in 10% sucrose. Focusing onAe. aegypti, cultures were maintained for multiple generations by feeding adult females protein- or tryptone-sugar meals. Ad libitum access to protein- or tryptone-sugar solutions protracted production of ecdysteroids by the ovaries, vitellogenin by the fat body and protease activity by the midgut albeit at levels that were lower than in blood-fed females. Females also exhibited semi-continual oogenesis and repressed host-seeking behavior.

Conclusions

Several anautogenous mosquitoes produce eggs when provided ad libitum access to protein- or peptide-sugar meals, but several aspects of oogenesis also differ from females that blood-feed.

Graphical Abstract
Loop mediated isothermal amplification of Clostridioides difficile isolates in gastrointestinal patients
Authors: Moosavian Mojtaba , Keshavarzi Razieyeh , Abbasi Montazeri Effat , Hajiani Eskandar
Published: April 2022

This study investigated the prevalence ofClostridioides difficileby culture, multiplex polymerase chain reaction (M-PCR), and loop mediated isothermal amplification (LAMP) in patients with suspectedC. difficileinfections (CDIs). Also, the results of three methods were compared. All stool specimens collected from CDI suspected patients were cultured on selectiveC. difficilecycloserine-cefoxitin fructose agar and incubated in an anaerobic jar up to 7 days. The bacterial isolates were identified using standard tests. Multiplex-PCR (M-PCR) was performed for detection oftcdA,tcdB, andtpigenes. The LAMP assay was performed to detect thetcdBgene ofC. difficile.C. difficilewas isolated from 20.0% (n = 10/50) of samples by culture. M-PCR showed that 34.0% (n = 17/50) of the specimens were positive forC. difficilebased on the presence oftpigene. Out of the 17C. difficile, 13 strains (76.0%) were positive fortcdBgene using M-PCR. However, the LAMP assay showed that 30.0% (15/50) of specimens were positive for the presence oftcdBgene. M-PCR and LAMP methods showed 100.0% sensitivity compared to the culture method. However, the specificity of the LAMP (87.5%) was relatively higher than the M-PCR (82.5%) compared to the culture. Based on the results of this study, the prevalence of toxigenicC. difficilestrains was high in suspected CDI patients. So, the differentiation between toxigenic and non-toxigenic strains is necessary. Our data showed that the LAMP assay is a good method for direct detection of toxigenicC. difficilestrains from stool specimens.
miRNA sequencing analysis of healthy and atretic follicles of chickens revealed that miR-30a-5p inhibits granulosa cell death via targeting Beclin1
Authors: He Haorong , Li Dongmei , Tian Yongtong , Wei Qinyao , Amevor Felix Kwame , Sun Congjiao , Yu Chunlin , Yang Chaowu , Du Huarui , Jiang Xiaosong , Ma Menggen , Cui Can , Zhang Zhichao , Tian Kai , Zhang Yao , Zhu Qing , Yin Huadong
Published: April 2022

Background

The egg production performance of chickens is affected by many factors, including genetics, nutrition and environmental conditions. These factors all play a role in egg production by affecting the development of follicles. MicroRNAs (miRNAs) are important non-coding RNAs that regulate biological processes by targeting genes or other non-coding RNAs after transcription. In the animal reproduction process, miRNA is known to affect the development and atresia of follicles by regulating apoptosis and autophagy of granulosa cells (GCs).

Results

In this study, we identified potential miRNAs in the atretic follicles of broody chickens and unatretic follicles of healthy chickens. We identified gga-miR-30a-5p in 50 differentially expressed miRNAs and found that gga-miR-30a-5p played a regulatory role in the development of chicken follicles. The function of miR-30a-5p was explored through the transfection test of miR-30a-5p inhibitor and miR-30a-5p mimics. In the study, we used qPCR, western blot and flow cytometry to detect granulosa cell apoptosis, autophagy and steroid hormone synthesis. Confocal microscopy and transmission electron microscopy are used for the observation of autophagolysosomes. The levels of estradiol (E2), progesterone (P4), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by ELISA. The results showed that miR-30a-5p showed a negative effect on autophagy and apoptosis of granulosa cells, and also contributed in steroid hormones and reactive oxygen species (ROS) production. In addition, the results obtained from the biosynthesis and dual luciferase experiments showed that Beclin1 was the target gene of miR-30a-5p. The rescue experiment conducted further confirmed that Beclin1 belongs to the miR-30a-5p regulatory pathway.

Conclusions

In summary, after deep miRNA sequencing on healthy and atretic follicles, the results indicated that miR-30a-5p inhibits granulosa cell death by inhibiting Beclin1.
The effect of initial and prior models on phase tensor inversion of distorted magnetotelluric data
Authors: Rung-Arunwan T. , Siripunvaraporn W. , Utada H.
Published: April 2022

Magnetotelluric (MT) data are often distorted by near-surface small-scale lateral heterogeneities. Inverting distorted MT data may produce artifacts or false anomalies, leading to unreliable interpretation. This problem can be avoided by inverting the phase tensor (PT), which is known to be free of galvanic distortion. However, PT inversion is known to strongly depend on the initial or prior model, because the PT itself does not contain absolute resistivity information. To obtain a reliable inversion result from a set of PT data, a proper initial or prior model is crucial. In this study, a one-dimensional mean resistivity profile estimated from the average sum-of-squared-elements impedance was chosen as an initial model, because it was proven to be less sensitive to galvanic distortion. Examples with synthetic data showed that PT inversion using such an initial and prior model is a viable approach for inverting galvanically distorted MT data. In addition, the present paper considers a situation, where the distortion is not purely galvanic. A simple synthetic study indicated that the PT is affected by inductive distortion, and thus, such inversion results should be interpreted with caution.

Graphic Abstract