bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in the placental pharmacokinetics of vedolizumab and ustekinumab during pregnancy in women with inflammatory bowel disease: a prospective multicentre study
Authors: Mitrova Katarina , Pipek Barbora , Bortlik Martin , Bouchner Ludek , Brezina Jan , Douda Tomas , Drasar Tomas , Drastich Pavel , Falt Premysl , Klvana Pavel , Leksa Vaclav , Novotny Ales , Svoboda Pavel , Skorpik Jan , Ulbrych Jan , Veinfurt Marek , Zborilova Blanka , Lukas Milan , Duricova Dana
Published: August 2021

Background:

Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease.

Methods:

Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery.

Results:

Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p = 0.001).

Conclusion:

Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor (TNF) agents.
Plasma ADAMTS13 and von Willebrand factor in diagnosis and prediction of prognosis in pulmonary arterial hypertension
Authors: Ahmed Abdulla , Ahmed Salaheldin , Rådegran Göran
Published: August 2021

To improve outcome in pulmonary arterial hypertension, earlier diagnosis and better prognostic assessments are required. We aimed to investigate the diagnostic and prognostic potential of plasma proteins related to pathways recognized in pulmonary arterial hypertension including coagulation, inflammation, and metabolism. Forty‐two proteins were analysed with proximity extension assay from plasma of 20 healthy controls and 150 patients, including (pulmonary arterial hypertension, n = 48, whereof 33 also during early treatment follow‐ups); chronic thromboembolic pulmonary hypertension (CTEPH, n = 20); pulmonary hypertension (PH) due to heart failure (HF) with preserved ejection fraction (HFpEF‐PH, n = 31); PH due to HF with reduced ejection fraction (HFrEF‐PH, n = 36); and HF without PH (Dyspnoea/HF‐non‐PH, n = 15). Patients’ haemodynamics were assessed by right heart catheterization. Plasma ADAMTS13 in incident pulmonary arterial hypertension was lower compared to the healthy controls (p = 0.055), as well as CTEPH (p < 0.0001), HFrEF‐PH (p < 0.0001), HFrEF‐PH (p < 0.0001), and Dyspnoea/HF‐non‐PH (p < 0.0001). Adjusted for age and sex, ADAMTS13 discriminated pulmonary arterial hypertension from the other disease groups with an AUC of 0.91 (sensitivity = 87.5%, and specificity = 78.4%). Higher plasma von Willebrand factor was associated with worse survival (log‐rank p = 0.0029), and a higher mortality rate (adjusted hazard ratio 1.002, 95% confidence interval 1–1.004; p = 0.041). Adjusted for age, sex, and combined with the ESC/ERS risk score, von Willebrand factor predicted mortality (median follow‐up 3.6 years) in pulmonary arterial hypertension with an AUC of 0.94 (sensitivity = 81.3%, and specificity=93.8%). ADAMTS13 may be a promising biomarker for early detection of PAH and von Willebrand factor as a candidate prognostic biomarker. The putative additional value of von Willebrand factor to the European multiparametric risk assessment strategy remains to be elucidated.
The Impact of Presence on Learning Transfer Intention in Virtual Reality Simulation Game
Authors: Choi Doo-Hun , Noh Ghee-Young
Published: August 2021

The three-dimensional (3D) virtual reality content is widely used for educational and training purposes, and there has been interest in how virtual reality environments influence users’ learning effect. Analyzing survey data collected from a game play, this study examined how presence in a 3D virtual reality car driving simulation game impacts players’ learning transfer intention through flow, arousal, and enjoyment. Using structural equation modeling, the results showed that presence was positively associated with flow and arousal, which in turn contributed to an increase in enjoyment of the game. The enjoyment played a significant role in elevating the players’ learning transfer intention. These results provide an understanding of the psychological mechanisms behind the impact of presence on learning transfer intention in a 3D virtual reality driving simulation game. Limitations and implications of the study are discussed in greater detail.
An Unusual Case of Severe Persistent Neonatal Thrombocytopenia in an Extremely Low Birth Weight, Extreme Preterm Neonate
Authors: Paul Mobin , Killikulangara Sadanandan Ananthen , Abraham Latha , Madany Pathrose Sophy , Varghese Dasary
Published: August 2021

Neonatal thrombocytopenia is a common hematological problem but refractory thrombocytopenia is very rare in neonates. A systematic and diligent workup will result in arriving at the proper diagnosis and providing accurate management in rare causes of neonatal thrombocytopenia. We report a case of severe refractory thrombocytopenia in an extremely low birth weight (ELBW)/extreme preterm baby who presented with early onset severe thrombocytopenia associated with anemia and required multiple platelet transfusions. After ruling out COVID-19 infection, sepsis and neonatal alloimmune thrombocytopenia (NAIT), the cause for severe refractory thrombocytopenia was diagnosed as Type II congenital amegakaryocytic thrombocytopenia (CAMT) by bone marrow examination and MPL gene mutation studies.
Synthesizing the Literature on Stress Velopharyngeal Insufficiency in Musicians: Recommendations for Music Educators
Authors: Behel Kensley , Evans Alison , Rennie-Salonen Bridget
Published: August 2021

Many musicians experience performance-related health problems (PRHPs), most of which are preventable. Music educators play a primary role in the prevention of PRHPs in the music classroom. Stress velopharyngeal insufficiency (SVPI) in wind musicians is a condition affecting soft palate closure, causing air to escape through the nose while blowing through the mouth into the instrument. Although SVPI is serious and potentially career ending for wind instrumentalists, there are limited resources for music educators on SVPI prevalence, causes, management, and prevention. Therefore, this synthesis of existing literature on SVPI in musicians provides music educators with awareness and understanding of SVPI. Information on SVPI symptoms, treatment pathways, prevention, and recommendations for practical solutions to manage SVPI in the music studio are given. A comprehensive understanding of terminology, symptoms, prevalence, and solutions may equip music educators to intervene more effectively in identifying SVPI in their classroom or studio.
Physiological and transcriptomic analyses to reveal underlying phenolic acid action in consecutive monoculture problem of Polygonatum odoratum
Authors: Ni Xianzhi , Jin Chenzhong , Liu Aiyu , Chen Yong , Hu Yihong
Published: August 2021

Background

The root rot of fragrant solomonseal (Polygonatum odoratum) has occurred frequently in the traditional P. odoratum cultivating areas in recent years, causing a heavy loss in yield and quality. The phenolic acids in soil, which are the exudates from the P. odoratum root, act as allelochemicals that contribute to the consecutive monoculture problem (CMP) of the medicinal plant. The aim of this study was to get a better understanding of P. odoratum CMP.

Results

The phenolic acid contents, the nutrient chemical contents, and the enzyme activities related to the soil nutrient metabolism in the first cropping (FC) soil and continuous cropping (CC) soil were determined, and the differentially expressed genes (DEGs) related to the regulation of the phenolic acids in roots were analyzed. The results showed that five low-molecule-weight phenolic acids were detected both in the CC soil and FC soil, but the phenolic acid contents in the CC soil were significantly higher than those in the FC soil except vanillic acid. The contents of the available nitrogen, available phosphorus, and available potassium in the CC soil were significantly decreased, and the activities of urease and sucrase in the CC soil were significantly decreased. The genomic analysis showed that the phenolic acid anabolism in P. odoratum in the CC soil was promoted. These results indicated that the phenolic acids were accumulated in the CC soil, the nutrient condition in the CC soil deteriorated, and the nitrogen metabolism and sugar catabolism of the CC soil were lowered. Meantime, the anabolism of phenolic acids was increased in the CC plant.

Conclusions

The CC system promoted the phenolic acid anabolism in P. odoratum and made phenolic acids accumulate in the soil.
Improving patient self-reporting of antihypertensive adverse drug events in primary care: a stepped wedge cluster randomised trial
Authors: Buchet-Poyau Karine , Occelli Pauline , Touzet Sandrine , Langlois-Jacques Carole , Figon Sophie , Dubois Jean-Pierre , Duclos Antoine , Chanelière Marc , Colin Cyrille , Rabilloud Muriel , Keriel-Gascou Maud
Published: August 2021

Background

About 25% of patients experience adverse drug events (ADE) in primary care, but few events are reported by the patients themselves. One solution to improve the detection and management of ADEs in primary care is for patients to report them to their general practitioner. The study aimed to assess the effect of a booklet designed to improve communication and interaction between patients treated with anti-hypertensive drugs and general practitioners on the reporting of ADEs.

Methods

A cluster randomized controlled cross-sectional stepped wedge open trial (five periods of 3 months) was conducted. A cluster was a group of general practitioners working in ambulatory offices in France. Adults consulting their general practitioner to initiate, modify, or renew an antihypertensive prescription were included. A booklet including information on cardiovascular risks, antihypertensive treatments, and ADE report forms was delivered by the general practitioner to the patient in the intervention group. The primary outcome was the reporting of at least one ADE by the patient to his general practitioner during the three-month period after enrolment. Two clusters were randomised by sequence for a total of 8 to receive the intervention. An intention-to-treat analysis was conducted. A logistic mixed model with random intercept was used.

Results

Sixty general practitioners included 1095 patients (median: 14 per general practitioner; range: 1–103). More patients reported at least one ADE to their general practitioner in the intervention condition compared to the control condition (aOR = 3.5, IC95 [1.2–10.1], p = 0.02). The modification and initiation of an antihypertensive treatment were also significantly associated with the reporting of ADEs (aOR = 4.4, CI95 [1.9–10.0], p <  0.001 and aOR = 11.0, CI95 [4.6–26.4], p <  0.001, respectively). The booklet delivery also improved patient satisfaction on general practitioner communication and high blood pressure management.

Conclusion

A booklet can improve patient self-reporting of ADEs to their general practitioners. Future research should assess whether it can improve general practitioner management of ADEs and patient’s health status.

Trial registration

Trial registry identifier NCT01610817 (2012/05/30).
Maternal psychological distress, education, household income, and congenital heart defects: a prospective cohort study from the Japan environment and children’s study
Authors: Saijo Yasuaki , Yoshioka Eiji , Sato Yukihiro , Azuma Hiroshi , Tanahashi Yusuke , Ito Yoshiya , Kobayashi Sumitaka , Minatoya Machiko , Ait Bamai Yu , Yamazaki Keiko , Itoh Sachiko , Miyashita Chihiro , Ikeda-Araki Atsuko , Kishi Reiko ,   the Japan Environment and Children’s Study (JECS) Group
Published: August 2021

Background

The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD.

Methods

We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD.

Results

A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050).

Conclusions

The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.
Identification of prognostic immune-related gene signature associated with tumor microenvironment of colorectal cancer
Authors: Wang Yuanyuan , Li Wei , Jin Xiaojing , Jiang Xia , Guo Shang , Xu Fei , Su Xingkai , Wang Guiqi , Zhao Zengren , Gu Xiaosong
Published: August 2021

Background

The tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC).

Methods

Transcriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database.

Results

Gene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717–0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates.

Conclusions

In this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.
Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma
Authors: Powles Thomas , Choueiri Toni K. , Motzer Robert J. , Jonasch Eric , Pal Sumanta , Tannir Nizar M. , Signoretti Sabina , Kaldate Rajesh , Scheffold Christian , Wang Evelyn , Aftab Dana T. , Escudier Bernard , George Daniel J.
Published: August 2021

Background

In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS) and overall survival (OS) versus everolimus in patients with advanced RCC after prior antiangiogenic therapy.

Methods

In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods. For on-treatment changes, PFS and OS were analyzed using fold change in biomarker levels at week 4. Biomarkers were considered prognostic if p < 0.05 and predictive if pinteraction < 0.05 for the interaction between treatment and biomarker.

Results

Hazard ratios for PFS and OS favored cabozantinib versus everolimus for both low and high baseline levels of all biomarkers (hazard ratios ≤0.78). In univariate analyses, low baseline HGF, AXL, and VEGF were prognostic for improvements in both PFS and OS with cabozantinib, and low HGF was prognostic for improvements in both PFS and OS with everolimus. Low AXL was predictive of relative improvement in PFS for cabozantinib versus everolimus. Results were generally consistent when baseline biomarkers were expressed as continuous variables, although none were predictive of benefit with treatment. In multivariable analysis, low baseline HGF was independently prognostic for improved PFS for both cabozantinib and everolimus; low HGF, GAS6, and VEGF were independently prognostic for improved OS with cabozantinib. No biomarkers were independently prognostic for OS with everolimus. On-treatment increases in some biomarkers appeared prognostic for PFS or OS with cabozantinib in univariate analyses; however, none were independently prognostic in multivariable analysis.

Conclusions

PFS and OS were improved with cabozantinib versus everolimus at high and low baseline levels of all biomarkers. Low baseline HGF was consistently identified as a prognostic biomarker for improved PFS or OS with cabozantinib or everolimus, supporting further prospective evaluation of the prognostic significance of HGF in advanced RCC.

Trial registration

ClinicalTrials.gov NCT01865747 (registered on 05/31/2013).
TACR2 is associated with the immune microenvironment and inhibits migration and proliferation via the Wnt/β-catenin signaling pathway in prostate cancer
Authors: Jianfeng Wang , Yutao Wang , Jianbin Bi
Published: August 2021

Background

The tachykinin receptor 2 (TACR2) is encoded by the tachykinin receptor correlation gene. Recent microarray analysis for prostate cancer suggests that TACR2 expression is associated with clinical phenotype and disease-free survival among patients with prostate cancer.

Results

TACR2 protein levels were lower in prostate cancer tissues than in adjacent normal prostate tissue. TACR2 expression significantly correlated with clinical stage, Gleason scores, and survival outcomes. TACR2 expression positively correlated with mast cells and negatively correlated with M2 macrophages. Overexpression of TACR2 promoted the migration and proliferation of prostate cancer cells by regulating the Wnt signaling pathway.

Conclusions

The TACR2-Wnt/β-catenin signaling pathway is critical in prostate cancer. TACR2 may affect tumor cells’ occurrence and development by changing the content of immune cells in the tumor microenvironment. These findings suggest that TACR2 may be a candidate molecular biomarker for prostate cancer therapy.
Development and validation of prognostic nomograms for patients with colon neuroendocrine neoplasms
Authors: Xu Ruitong , Zhou Bingrong , Hu Ping , Xue Bingyan , Gu Danyang , Li Xiaolin , Tang Qiyun
Published: August 2021

Background

Colon neuroendocrine neoplasms (NENs) have one of the poorest median overall survival (OS) rates among all NENs. The American Joint Committee on Cancer (AJCC) tumor–node–metastasis (TNM) staging system—currently the most commonly used prediction model—has limited prediction accuracy because it does not include parameters such as age, sex, and treatment. The aim of this study was to construct nomograms containing various clinically important parameters to predict the prognosis of patients with colon NENs more accurately.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a retrospective analysis of colon NENs diagnosed from 1975 to 2016. Data were collected from 1196 patients; almost half were female (617/1196, 51.6%), and the average age was 61.94 ± 13.05 years. Based on the age triple cut-off values, there were 396 (33.1%), 408 (34.1%), and 392 (32.8%) patients in age groups 0–55 years, 55–67 years, and ≥ 68 years, respectively. Patients were randomized into training and validation cohorts (3:1). Independent prognostic factors were used for construction of nomograms to precisely predict OS and cancer-specific survival (CSS) in patients with colon NENs.

Results

Multivariate analysis showed that age ≥ 68 years, sex, tumor size, grade, chemotherapy, N stage, and M stage were independent predictors of OS. In the validation cohort, the Concordance index (C-index) values of the OS and CSS nomograms were 0.8345 (95% confidence interval [CI], 0.8044–0.8646) and 0.8209 (95% CI, 0.7808–0.861), respectively. C-index also indicated superior performance of both nomograms (C-index 0.8347 for OS and 0.8668 for CSS) compared with the AJCC TNM classification (C-index 0.7159 for OS and 0.7366 for CSS).

Conclusions

We established and validated new nomograms for more precise prediction of OS and CSS in patients with colon NENs to facilitate individualized clinical decisions.
Role of open cerclage wiring in patients with comminuted fractures of the femoral shaft treated with intramedullary nails
Authors: Wang Tzu-Hao , Chuang Hao-Chun , Kuan Fa-Chuan , Hong Chih-Kai , Yeh Ming-Long , Su Wei-Ren , Hsu Kai-Lan
Published: August 2021

Introduction

The role of open cerclage wiring in comminuted femoral shaft fracture treatment with intramedullary nails remains unclear. Here, we analyzed the effect of open cerclage wiring and the risk factors for nonunion after interlocking nailing in comminuted femoral shaft fracture treatment. We hypothesized that open cerclage wiring can be applied in patients with severe comminuted femoral shaft fractures without affecting bone healing.

Patients and methods

This retrospective cohort study used data from consecutive patients who underwent interlocking nail fixation of a comminuted femoral shaft fracture between January 1, 2009, and December 31, 2016. First, eligible patients were divided into the wire and no wire groups according to the surgical technique used, and their union rate was recorded. The patients were then divided into the union and nonunion groups, and their perioperative data were analyzed.

Results

In total, 71 comminuted femoral shaft fractures treated with interlocking nail fixation were included: 38 fractures (53.5%) augmented with the open wiring technique and 33 reduced with closed or mini-open techniques without wiring. The wire group demonstrated significant improvements in fracture reduction compared with the no wire group, whereas no significant difference was observed in the union rate between the wire and no wire groups (p= 0.180). Moreover, 46 (65%) of 71 fractures achieved union smoothly, and no significant difference was observed in any perioperative data between the union and nonunion groups.

Discussion

Augmentation with open cerclage wiring is indicated for comminuted femoral shaft fractures treated with intramedullary nails, even when the fragments are large or greatly displaced. Thus, open cerclage wiring can be used for fracture treatment without decreasing the union rate.
Septic shock complicated by disseminated herpes simplex virus-1 infection: a case report
Authors: Boquet Amélie , Boulay Guillaume , Hautin Etienne , Mottard Nicolas
Published: August 2021

Background

Herpes virus remains dormant in human cells and could reactivate under immunosuppressed conditions, such as prolonged critical illnesses. The phenomenon of viral replication during intensive care is well known, even in patients without a history of immunosuppression, but it usually does not have a clinical impact. Systemic reactivation leads to viral DNA in blood. It remains unclear whether this replication is a marker of morbimortality or a true pathogenic process. Therefore, it is unclear what medical treatment is most appropriate for simple replication. In organ damage suspected to be induced by herpes virus, there is no consensus on the most appropriate treatment duration. Here, we report a rarely described case of multiorgan failure implicating herpes simplex virus and discuss its treatment.

Case report

A 53-year-old Caucasian immunosuppressed woman was admitted to the intensive care unit for septic shock. She presented pneumonia due to Klebsiella pneumoniae. Two weeks after admission, she showed multiorgan failure with acute respiratory distress syndrome and circulation failure. She had digestive and cutaneous lesions typical of herpes simplex virus 1. Blood and respiratory polymerase chain reaction was strongly herpes simplex virus-1 positive. No other bacteria, fungi, or viruses were found. The evolution was rapidly favorable after the initiation of antiviral treatment. Treatment was stopped after 3 weeks of well-conducted antiviral therapy. Curative-dose treatment was interrupted despite continuous strongly positive blood polymerase chain reaction results. In this context, prophylactic treatment was continued.

Conclusion

We report an exceptional presentation of multiorgan failure in the intensive care unit due to herpes simplex virus-1. The diagnosis was made based on typical herpes simplex virus-1 visceral lesions and the absence of other responsible microorganisms. Intense viral replication is a key diagnostic element. There is no consensus regarding the most appropriate treatment duration, but such decisions should not be based on blood polymerase chain reaction.
Mask decontamination methods (model N95) for respiratory protection: a rapid review
Authors: Probst Livia Fernandes , Guerrero Ana Tereza Gomes , Cardoso Andréia Insabralde de Queiroz , Grande Antonio Jose , Croda Mariana Garcia , Venturini James , Fonseca Maria Cristina de Camargo , Paniago Anamaria Mello Miranda , Barreto Jorge Otávio Maia , de Oliveira Sandra Maria do Vale Leone
Published: August 2021

Background

N95 respiratory protection masks are used by healthcare professionals to prevent contamination from infectious microorganisms transmitted by droplets or aerosols.

Methods

We conducted a rapid review of the literature analyzing the effectiveness of decontamination methods for mask reuse. The database searches were carried out up to September 2020. The systematic review was conducted in a way which simplified the stages of a complete systematic review, due to the worldwide necessity for reliable fast evidences on this matter.

Results

A total of 563 articles were retrieved of which 48 laboratory-based studies were selected. Fifteen decontamination methods were included in the studies. A total of 19 laboratory studies used hydrogen peroxide, 21 studies used ultraviolet germicidal irradiation, 4 studies used ethylene oxide, 11 studies used dry heat, 9 studies used moist heat, 5 studies used ethanol, two studies used isopropanol solution, 11 studies used microwave oven, 10 studies used sodium hypochlorite, 7 studies used autoclave, 3 studies used an electric rice cooker, 1 study used cleaning wipes, 1 study used bar soap, 1 study used water, 1 study used multi-purpose high-level disinfection cabinet, and another 1 study used chlorine dioxide. Five methods that are promising are as follows: hydrogen peroxide vapor, ultraviolet irradiation, dry heat, wet heat/pasteurization, and microwave ovens.

Conclusions

We have presented the best available evidence on mask decontamination; nevertheless, its applicability is limited due to few studies on the topic and the lack of studies on real environments.
Prevalence of hypertension in Ghanaian society: a systematic review, meta-analysis, and GRADE assessment
Authors: Atibila Fidelis , Hoor Gill ten , Donkoh Emmanuel Timmy , Wahab Abdul Iddrisu , Kok Gerjo
Published: August 2021

Background

Hypertension has become an important public health concern in the developing world owing to rising prevalence and its adverse impact on ailing health systems. Despite being a modifiable risk factor for cardiovascular disease, hypertension has not received the needed attention in Ghana as a result of various competing interests for scarce health resources. This systematic review and meta-analysis provides a comprehensive and updated summary of the literature on the prevalence of hypertension in Ghana.

Methods

Major databases such as MEDLINE, EMBASE, and Google Scholar and local thesis repositories were accessed to identify population-based studies on hypertension among Ghanaians. Data extracted from retrieved reports were screened independently by two reviewers. The quality of eligible studies was evaluated and reported. A reliable pooled estimate of hypertension prevalence was calculated utilizing a random-effects model and reported according to the GRADE framework. Additionally, a meta-regression analysis was performed to analyze the contribution of study-level variables to variance in hypertension prevalence.

Results

In general, a total of 45,470 subjects (n = 22,866 males and 22,604 females) were enrolled from urban (n = 12), rural (n = 8), and mixed populations (n = 7). Blood pressure (BP) was measured across studies according to a validated and clinically approved protocol by trained field workers or healthcare workers including nurses and physicians. A combined total of 30,033 participants across twenty studies reporting on the population prevalence of hypertension were pooled with 10,625 (35.4%) identified to satisfy study criteria for elevated BP. The pooled prevalence across 24 studies was 30.3% (95% CI 26.1–34.8%) after fitting a random effects model. Prevalence of hypertension was 30.1% (95% CI 25.6–36.0%) among females and 34.0% (95% CI 28.5–40.0%) among males. Significant differences in pooled estimates across regions emerged from subgroup comparisons of regional estimates with an increasing trend in the north-to-south direction and with increasing age. Compared to rural settings, the burden of hypertension in urban populations was significantly higher. Age structure and population type accounted for 65.0% of the observed heterogeneity in hypertension estimates.

Conclusions

The prevalence of hypertension in Ghana is still high. The gap in hypertension prevalence between rural and urban populations is closing especially in elderly populations. These findings must claim the attention of public health authorities in Ghana to explore opportunities to reduce rural hypertension.

Systematic review registration

The protocol for this review has been published previously with PROSPERO (CRD42020215829).
Gluten in pharmaceutical products: a scoping review
Authors: Lizano-Díez Irene , Mariño Eduardo L. , Modamio Pilar
Published: August 2021

Background

Celiac disease (CD) is one of the most common gluten-related disorders. Although the only effective treatment is a strict gluten-free diet, doubts remain as to whether healthcare professionals take this restriction into consideration when prescribing and dispensing medicines to susceptible patients. This scoping review aimed to find out the current evidence for initiatives that either describe the gluten content of medicines or intend to raise awareness about the risk of prescribing and dispensing gluten-containing medicines in patients with CD and other gluten-related disorders.

Methods

A scoping review was conducted using three search strategies in PubMed/MEDLINE, TripDatabase and Web of Science in April 2021, following the PRISMA extension for scoping reviews (PRISMA-ScR). References from included articles were also examined. Two researchers screened the articles and results were classified according to their main characteristics and outcomes, which were grouped according to the PCC (Population, Concept and Context) framework. The initiatives described were classified into three targeted processes related to gluten-containing medicines: prescription, dispensation and both prescription and dispensation.

Results

We identified a total of 3146 records. After the elimination of duplicates, 3062 articles remained and ultimately 13 full texts were included in the narrative synthesis. Most studies were conducted in the US, followed by Canada and Australia, which each published one article. Most strategies were focused on increasing health professional’s knowledge of gluten-containing/gluten-free medications (n = 8), which were basically based on database development from manufacturer data. A wide variability between countries on provided information and labelling of gluten-containing medicines was found.

Conclusion

Initiatives regarding the presence of gluten in medicines, including, among others, support for prescribers, the definition of the role of pharmacists, and patients’ adherence problems due to incomplete labelling of the medicines, have been continuously developed and adapted to the different needs of patients. However, information is still scarce, and some aspects have not yet been considered, such as effectiveness for the practical use of solutions to support healthcare professionals.
Household food insecurity and coping strategies in Southern Ethiopia
Authors: Melese Mesfin , Tilahun Minyahel , Alemu Mebratu
Published: August 2021

Background

Hunger and undernourishment are the main challenges of today’s world and 960 million people are hungry and undernourished. Food insecurity is an enduring, critical challenge in Ethiopia. Majority of the previous studies overlooked relevant determinant factors which affect the occurrence of food insecurity. This study aims to investigate household level food insecurity determinate factors and coping strategies used in the study area.

Method

Explanatory and descriptive research was designed to assess household food insecurity and coping strategies in Analemmo district of southern Ethiopia. A multi-stage purposive sampling technique was used for the purpose of this study. Two hundred households were selected systematically following list of food insecure households. Econometric models were employed using binary logit model. Household calorie acquisition was calculated to categorize households into food secure and food insecurely status.

Results

The survey result showed that 64% of the respondents were food insecure. Variables such as agro-ecology, age and education status, number of oxen, soil and water conservation, amount of credit, cultivated land size and receiving remittance were negatively but significantly (P < 0.05) affected households' food insecurity level. Female and young groups of the community were more food insecure as compared to others groups. The community was coping food shortage by relying on less preferred and less expensive food followed by participating in off-farm activities and borrowing food. Housesholds in the study area were utilizing less preferred foods to cope up food shortage and starvation.

Conclusion

Efforts of different developmental organizations should give due emphasis to household's wealth level, female-headed household and young and old-aged members of the community. Crop land production supported by modern agricultural technologies and information can reduce agricultural risks, and enhance productivity per unit land.
Counting sea lions and elephants from aerial photography using deep learning with density maps
Authors: Padubidri Chirag , Kamilaris Andreas , Karatsiolis Savvas , Kamminga Jacob
Published: August 2021

Background

The ability to automatically count animals is important to design appropriate environmental policies and to monitor their populations in relation to biodiversity and maintain balance among species. Out of all living mammals on Earth, 60% are livestock, 36% humans, and only 4% are animals that live in the wild. In a relatively short period, development of human civilization caused a loss of 83% of wildlife and 50% of plants. The rate of species extinction is accelerating. Traditional wildlife surveys provide rough population estimates. However, emerging technologies, such as aerial photography, allow to perform large-scale surveys in a short period of time with high accuracy. In this paper, we propose the use of computer vision, through deep learning (DL) architecture, together with aerial photography and density maps, to count the population of Steller sea lions and African elephants with high precision.

Results

We have trained two deep learning models, a basic UNet without any feature extractor (Model-1) and another with the EfficientNet-B5 feature extractor (Model-2). We measured the model’s prediction accuracy, using Root Mean Square Error (RMSE) for the predicted and actual animal count. The results showed an RMSE of 1.88 and 0.60 to count Steller sea lions and African elephants, respectively, regardless of complex background, different illumination conditions, heavy overlapping and occlusion of the animals.

Conclusions

Our proposed solution performed very well in the counting prediction problem, with relatively low training parameters and minimum annotation. The approach adopted, combining DL and density maps, provided better results than state-of-art deep learning models used for counting, indicating that the proposed method has the potential to be used more widely in large-scale wildlife surveying projects and initiatives.
CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/β-catenin pathway
Authors: Shi Qi , Zhou Chuanwen , Xie Rui , Li Miaomiao , Shen Peng , Lu Yining , Ma Shijie
Published: August 2021

Background

Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism.

Methods

The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer.

Results

CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo.

Conclusion

Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.
Case Studies in Pediatric Lipid Disorders and Their Management
Authors: Ashraf Ambika P , Sunil Bhuvana , Bamba Vaneeta , Breidbart Emily , Brar Preneet Cheema , Chung Stephanie , Gupta Anshu , Khokhar Aditi , Kumar Seema , Lightbourne Marissa , Kamboj Manmohan K , Miller Ryan S , Patni Nivedita , Raman Vandana , Shah Amy S , Wilson Don P , Kohn Brenda
Published: August 2021

Context

Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood.

Aim

In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia.

Cases

We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing.

Conclusion

Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.
Effect of Metabolite Levels on Type 2 Diabetes Mellitus and Glycemic Traits: A Mendelian Randomization Study
Authors: Sun Yue , Lu Ya-Ke , Gao Hao-Yu , Yan Yu-Xiang
Published: August 2021

Objective

To assess the causal associations of plasma levels of metabolites with type 2 diabetes mellitus (T2DM) and glycemic traits.

Methods

Two-sample mendelian randomization (MR) was conducted to assess the causal associations. Genetic variants strongly associated with metabolites at genome-wide significance level (P < 5 × 10−8) were selected from public genome-wide association studies, and single-nucleotide polymorphisms of outcomes were obtained from the Diabetes Genetics Replication and Meta-analysis consortium for T2DM and from the Meta-Analyses of Glucose and Insulin-related Traits Consortium for fasting glucose, insulin, and glycated hemoglobin (HbA1c). The Wald ratio and inverse-variance weighted methods were used for analyses, and MR-Egger was used for sensitivity analysis.

Results

The β estimates per 1-SD increase of arachidonic acid (AA) level was 0.16 (95% CI, 0.078-0.242; P < 0.001). Genetic predisposition to higher plasma AA levels were associated with higher fasting glucose levels (β 0.10 [95% CI, 0.064-0.134], P < 0.001), higher HbA1c levels (β 0.04 [95% CI, 0.027-0.061]), and lower fasting insulin levels (β -0.025 [95% CI, -0.047 to -0.002], P = 0.033). Besides, 2-hydroxybutyric acid (2-HBA) might have a positive causal effect on glycemic traits.

Conclusions

Our findings suggest that AA and 2-HBA may have causal associations on T2DM and glycemic traits. This is beneficial for clarifying the pathogenesis of T2DM, which would be valuable for early identification and prevention for T2DM.
Mechanisms of Weight Loss After Obesity Surgery
Authors: Akalestou Elina , Miras Alexander D , Rutter Guy A , le Roux Carel W
Published: August 2021

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota, and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surgery.
Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma
Authors: Lin Andrew L , Tabar Viviane , Young Robert J , Cohen Marc , Cuaron John , Yang T Jonathan , Rosenblum Marc , Rudneva Vasilisa A , Geer Eliza B , Bodei Lisa
Published: August 2021

Context

Aggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors.

Methods

We provide follow-up data on a previously reported patient with a hypermutated recurrent tumor. The patient in this report provided written informed consent for tumor sequencing and review of medical records on an institutional review board–approved research protocol (NCT01775072).

Results

This patient with a corticotroph pituitary carcinoma with alkylator-induced somatic hypermutation has remained on treatment with ipilimumab and nivolumab for 3.5 years and remains clinically well. After an initial partial response to checkpoint inhibitors, she has had several recurrences that have undergone immunoediting of subclonal mutations, which have been effectively treated with continuation of immunotherapy, surgery, external beam radiation, and 177Lu-DOTATATE. Following external beam radiotherapy (RT), she had radiographic evidence of an abscopal response at a distant site of disease suggesting a synergism between checkpoint inhibitors and RT. Following treatment with 177Lu-DOTATATE, the patient had a partial response with a 61% reduction in volume of the target lesion.

Conclusion

In patients with aggressive pituitary tumors, treatment with checkpoint inhibitors may trigger an abscopal response from RT. With appropriate selection, an additional efficacious treatment, 177Lu-DOTATATE, may be available for a limited number of patients with aggressive pituitary tumors, including patients who have progressed on temozolomide and exhibit increased somatostatin receptor expression on 68Ga-DOTATATE positron emission tomography.