bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory assays of VWF activity and use of desmopressin trials in the diagnosis of VWD: a systematic review and meta-analysis
Authors: Kalot Mohamad A. , Husainat Nedaa , Abughanimeh Omar , Diab Osama , El Alayli Abdallah , Tayiem Sammy , Madoukh Bader , Dimassi Ahmad , Qureini Aref , Ameer Barbara , Eikenboom Jeroen , Giraud Nicolas , Haberichter Sandra , Jacobs-Pratt Vicky , Konkle Barbara A. , McRae Simon , Montgomery Robert , O’Donnell James S. , Brignardello-Petersen Romina , Flood Veronica , Connell Nathan T. , James Paula , Mustafa Reem A.
Published: February 2022

von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment are important to prevent and treat these symptoms. We systematically reviewed the accuracy of any von Willebrand factor (VWF) activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and the certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR, VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio, and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appear to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with suspected VWD type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD.
Cholangiocarcinoma presenting as dysphagia and misdiagnosed as gastritis: a case report
Authors: Wang Chao , Zhang Baoyue , Peng Runmei , Zuo Zan , Cheng Hongzhong , Zhu Jun , Chen Tianxing , Song Zhengji
Published: February 2022

Background

Heterotopic tumor is a rare disease. Thus far, no cases of heterotopic cholangiocarcinoma have been reported in the world. Cholangiocarcinoma mainly metastasizes by direct invasion, and it can lead to liver metastasis in its advanced stage. There were few clinical cases of gastric metastasis in advanced tumors, mainly seen in breast cancer, lung cancer, liver cancer, malignant melanoma, choriocarcinoma, and hematological tumors. Metastases of cholangiocarcinoma to the stomach also are exceptionally rare.

Case presentation

A 58-year-old man was admitted to the hospital because of difficulty swallowing for one year. Upon gastroscopy, we found the tumor at the region of the cardia and gastric fundus. Macroscopical appearance of the tumor suggested its malignant nature. Computed tomography (CT) findings showed that the wall of the cardia, fundus, and stomach body were thickened, suggesting a tumor. Because the patient had obvious difficulty swallowing, we invited cardiothoracic surgeons for consultation. They considered that the patient had definite mechanical obstruction in the lower esophagus; hence, they performed an operation. Immunohistochemical staining revealed low-to-medium differentiated adenocarcinoma (containing mucinous adenocarcinoma components) of biliary origin.

Conclusions

We highlight the importance of the endoscopic biopsy of gastric tumor. However, when its results are inconsistent with the clinician’s judgment, further examination is required. Endoscopic ultrasonography and enhanced CT may be a good choice. If necessary, on the premise of patient acceptance, the diagnosis could be confirmed after surgical excision. Here we report a case of a patient with heterotopic cholangiocarcinoma in the gastric fundus. The most common tissue ectopias in the digestive tract include esophagogastric gastric mucosal ectopia, duodenal gastric mucosal ectopia, and gastric mucosal small intestinal ectopia. Thus far, there have been no reports of ectopic cholangiocarcinoma and associated cancer in the stomach. In addition, metastases of cholangiocarcinoma to the stomach are also exceptionally rare, and most of them are due to a direct invasion. The discovery of the primary lesion is an important clue for the reliable diagnosis in such cases.
Seasonal COVID-19 surge related hospital volumes and case fatality rates
Authors: Ebinger Joseph E. , Lan Roy , Driver Matthew , Sun Nancy , Botting Patrick , Park Eunice , Davis Tod , Minissian Margo B. , Coleman Bernice , Riggs Richard , Roberts Pamela , Cheng Susan
Published: February 2022

Background

Seasonal and regional surges in COVID-19 have imposed substantial strain on healthcare systems. Whereas sharp inclines in hospital volume were accompanied by overt increases in case fatality rates during the very early phases of the pandemic, the relative impact during later phases of the pandemic are less clear. We sought to characterize how the 2020 winter surge in COVID-19 volumes impacted case fatality in an adequately-resourced health system.

Methods

We performed a retrospective cohort study of all adult diagnosed with COVID-19 in a large academic healthcare system between August 25, 2020 to May 8, 2021, using multivariable logistic regression to examine case fatality rates across 3 sequential time periods around the 2020 winter surge: pre-surge, surge, and post-surge. Subgroup analyses of patients admitted to the hospital and those receiving ICU-level care were also performed. Additionally, we used multivariable logistic regression to examine risk factors for mortality during the surge period.

Results

We studied 7388 patients (aged 52.8 ± 19.6 years, 48% male) who received outpatient or inpatient care for COVID-19 during the study period. Patients treated during surge (N = 6372) compared to the pre-surge (N = 536) period had 2.64 greater odds (95% CI 1.46–5.27) of mortality after adjusting for sociodemographic and clinical factors. Adjusted mortality risk returned to pre-surge levels during the post-surge period. Notably, first-encounter patient-level measures of illness severity appeared higher during surge compared to non-surge periods.

Conclusions

We observed excess mortality risk during a recent winter COVID-19 surge that was not explained by conventional risk factors or easily measurable variables, although recovered rapidly in the setting of targeted facility resources. These findings point to how complex interrelations of population- and patient-level pandemic factors can profoundly augment health system strain and drive dynamic, if short-lived, changes in outcomes.
Effectiveness of emergency obstetric care training at the regional level in Ukraine: a non-randomized controlled trial
Authors: Mogilevkina Iryna , Gurianov Vitaliy , Lindmark Gunilla
Published: February 2022

Background

Emergency obstetric care training, using Advances in Labour and Risk Management (ALARM) International Program (AIP) was implemented in Ukraine, a country with universal access to skilled perinatal and obstetric care but restricted resources. A total of 577 providers (65.5% of total) from 28 maternal clinics attended a 5-day training session focused on the five main causes of maternal mortality, with hands-on skill workshops, pre- and post- tests, and an objective structured clinical examination. The effects of this emergency obstetric care training on maternal outcomes is the subject of this paper.

Methods

A non-randomized controlled trial was conducted. The pilot areas where the training was implemented consisted of 64 maternity clinics of which 28 were considered as cases and 36 non-participating clinics were the referents. Data on maternal outcomes were collected for a 2-year span (2004-2005) prior to the trainings, which took place 2006-2007 and again after implementation of the trainings, from 2008 to 2009. Information was collected from 189,852 deliveries. Outcomes for the study were incidences of operative delivery and postpartum hemorrhage. Non-parametric statistics, meta-analyses, and difference in difference (DID) estimation were used to assess the effect of the AIP on maternal indices.

Results

DID analysis showed that after the training, compared to the referents, the cases had significant reduction of blood transfusions (OR: 0.56; 95%CI: 0.48-0.65), plasma transfusions (OR: 0.70; 95%CI: 0.63-0.78), and uterus explorations (OR: 0.64; 95%CI: 0.59-0.69). We observed a non-significant reduction of postpartum hemorrhage ≥1000 ml (OR: 0.92; 95%CI: 0.81-1.04; P = 0.103). Utilization of vacuum extraction for vaginal delivery increased (OR: 2.86; 95%CI: 1.80-4.57), as well as forceps assisted delivery (OR: 1.80; 95%CI: 1.00-3.25) and cesarean section (OR: 1.11; 95%CI: 1.06-1.17). There was no change in the occurrence of postpartum hysterectomy and maternal mortality.

Conclusions

After one week of Emergency Obstetrics Care training of the obstetric staff in a setting with universal access to perinatal and obstetric care but restricted resources, an association with the reduction of postpartum hemorrhage related interventions was observed. The effects on the use of vacuum extraction and cesarean section were minimal.

Trial registration

Retrospectively registered 071212007807 from 07/12/2012.
Chemotherapy versus chemoradiotherapy for FIGO stages IB1 and IIA1 cervical squamous cancer patients with lymphovascular space invasion: a retrospective study
Authors: Zhang Hao , Yu Rao , Zhang Lan , Wang Rong , Xiao Lin
Published: February 2022

Purpose

To evaluate the impact of different adjuvant therapy on IB1 and IIA1 stage cervical squamous cell cancer patients with lymphovascular space invasion. It also aimed to analyze the relationship between lymphovascular space invasion and other clinical pathological characteristics on IB1 and IIA1 stage cervical squamous cell cancer patients.

Methods

This retrospective observational study collected data of FIGO stages IB1 and IIA1 squamous cervical cancer patients at the First Affiliated Hospital of Chongqing Medical University between 2014 and 2018. A correlation analysis between lymphovascular space invasion and other clinical or pathological factors was conducted. Prognosis analysis of patients with lymphovascular space invasion were performed to assess associations between clinical-pathological characteristics and survival.

Results

A total of 357 women were identified including 110 (30.8%) with lymphovascular space invasion, 247 (69.2%) without lymphovascular space invasion. Both middle 1/3 cervical stromal invasion (p = 0.000) and deep 1/3 cervical stromal invasion (p = 0.000) were independently associated with lymphovascular space invasion. Among lymphovascular space involved women, tumor differentiation (P = 0.001) and postoperative therapy (P = 0.036) had a significant influence on disease recurrence. Multivariate analysis showed that lymph node metastasis (P = 0.017), poorer tumor differentiation (P = 0.036) and postoperative chemotherapy alone (P = 0.021) can increase the risk of tumor relapse.

Conclusion

Our study suggested that the presence of deep stromal invasion independently increases the risk of lymphovascular space invasion. Compared with chemotherapy, chemoradiotherapy seems to improve progression-free survival in squamous cervical cancer patients with lymphovascular space invasion.
Assessing the role of adolescent hormonal contraceptive use on risk for depression: a 3-year longitudinal study protocol
Authors: Zareian Bita , Anderl Christine , LeMoult Joelle , Galea Liisa A. M. , Prior Jerilynn C. , Rights Jason D. , Ross Colin J. , Ge Sabrina , Hayward Annie C. , Chen Frances S.
Published: February 2022

Background

The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females’ risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning.

Methods

Using a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels.

Discussion

In this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.
Trends in total fertility rate in Ghana by different inequality dimensions from 1993 to 2014
Authors: Agbaglo Ebenezer , Agbadi Pascal , Tetteh Justice Kanor , Ameyaw Edward Kwabena , Adu Collins , Nutor Jerry John
Published: February 2022

Background

The past few decades witnessed a considerable decline in total fertility rates globally. However in Ghana, there has been a slight increase in the fertility rate with little understanding of the reason for the increment. To understand this change, it is important to first examine the trend over a considerable period of time while taking into consideration some important inequality dimensions. This informed the need for this present study as we examined the trends in total fertility rate in Ghana by different inequality dimensions from 1993 to 2014.

Methods

Data from the 1993–2014 Ghana Demographic and Health Surveys were used for the study, and we relied on the World Health Organization’s (WHO) Health Equity Assessment Toolkit (HEAT) software for the analysis. The analysis involved disaggregation of TFR by wealth index, education, place of residence and region. This was followed by the estimation of inequality by Difference, Population Attributable Risk, Ratio and Population Attributable Fraction. In the analysis, we set the statistical significance at a 95% confidence interval.

Results

For all surveys, the total fertility rate was consistently highest among the poorest women (7.00, 6.28, 6.77, 6.61 and 6.29 in 1993, 1998, 2003, 2008 and 2014, respectively). The highest total fertility rate was recorded among women with no formal education in all the survey years. For instance, in the 2014 survey, the total fertility rate for women with no formal education was 5.98 and those with secondary/higher had a total fertility rate of 3.40. Women in rural areas had a higher total fertility rate compared to those in urban areas (4.90 vs. 3.40 in 2014). In terms of sub-national regions, the Northern region was the region where women consistently had the highest total fertility rate.

Conclusion

There is a need for a collective effort to design interventions and policies to create awareness among the people of Ghana especially girls and women on the implications of high fertility.
Hygiene management for long-term ventilated persons in the home health care setting: a scoping review
Authors: Hoeppchen Isabel , Walter Carola , Berger Stefanie , Brandauer Anna , Freywald Nicole , Kutschar Patrick , Lex Katharina Maria , Strobl Annemarie , Gnass Irmela
Published: February 2022

Background

Evidence and recommendations for hygiene management in home mechanical ventilation (HMV) are rare. In Germany, few regionally limited studies show poor hygiene management or a lack of its implementation. This scoping review of international literature identified the evidence in hygiene management for ventilated patients in the home care setting which has to be implemented for infection prevention and control.

Methods

A review of international literature was conducted in CINAHL, PubMed and Web of Science. The search focused on four key domains: HMV, hygiene management, home care setting, and methicillin-resistant Staphylococcus aureus (MRSA). Data of included studies were extracted using a data charting sheet. Extracted data were assigned to the categories (1) study description, (2) setting and participants, and (3) hygiene management.

Results

From 1,718 reviewed articles, n = 8 studies met inclusion criteria. All included studies had a quantitative study design. The approaches were heterogeneous due to different settings, study populations and types of ventilation performed. Regarding aspects of hygiene management, most evidence was found for infectious critical activities (n = 5), quality management for hygiene (n = 4), and training and education (n = 4). This review identified research gaps concerning kitchen hygiene, relatives and visitors of HMV patients, and waste management (n = 0).

Discussion

Overall evidence was rather scarce. Consequently, this review could not answer all underlying research questions. No evidence was found for measures in hygiene management relating to ventilated patients’ relatives. Evidence for kitchen hygiene, waste management and interaction with relatives is available for inpatient care settings. However, this may not be transferable to outpatient care. Binding legal requirements and audits may help regulate the implementation of HMV hygiene measures.

Conclusion

Infection control programmes included qualified personnel, hygiene plans, and standards for MRSA and multidrug-resistant organisms (MDRO). The appropriateness of hygiene management measures for outpatient care is the basis for their application in practice.
Long COVID 12 months after discharge: persistent symptoms in patients hospitalised due to COVID-19 and patients hospitalised due to other causes—a multicentre cohort study
Authors: Rivera-Izquierdo Mario , Láinez-Ramos-Bossini Antonio Jesús , de Alba Inmaculada Guerrero-Fernández , Ortiz-González-Serna Rocío , Serrano-Ortiz Álvaro , Fernández-Martínez Nicolás Francisco , Ruiz-Montero Rafael , Cervilla Jorge A.
Published: February 2022

Background

Long-term-specific sequelae or persistent symptoms (SPS) after hospitalisation due to COVID-19 are not known. The aim of this study was to explore the presence of SPS 12 months after discharge in survivors hospitalised due to COVID-19 and compare it with survivors hospitalised due to other causes.

Methods

Prospective cohort study, the Andalusian Cohort of Hospitalised patients for COVID-19 (ANCOHVID study), conducted in 4 hospitals and 29 primary care centres in Andalusia, Spain. The sample was composed of 906 adult patients; 453 patients hospitalised due to COVID-19 (exposed) and 453 hospitalised due to other causes (non-exposed) from March 1 to April 15, 2020, and discharged alive. The main outcomes were (1) the prevalence of SPS at 12 months after discharge and (2) the incidence of SPS after discharge. Outcome data at 12 months were compared between the exposed and non-exposed cohorts. Risk ratios were calculated, and bivariate analyses were performed.

Results

A total of 163 (36.1%) and 160 (35.3%) patients of the exposed and non-exposed cohorts, respectively, showed at least one SPS at 12 months after discharge. The SPS with higher prevalence in the subgroup of patients hospitalised due to COVID-19 12 months after discharge were persistent pharyngeal symptoms (p<0.001), neurological SPS (p=0.049), confusion or memory loss (p=0.043), thrombotic events (p=0.025) and anxiety (p=0.046). The incidence of SPS was higher for the exposed cohort regarding pharyngeal symptoms (risk ratio, 8.00; 95% CI, 1.85 to 36.12), confusion or memory loss (risk ratio, 3.50; 95% CI, 1.16 to 10.55) and anxiety symptoms (risk ratio, 2.36; 95% CI, 1.28 to 4.34).

Conclusions

There was a similar frequency of long-term SPS after discharge at 12 months, regardless of the cause of admission (COVID-19 or other causes). Nevertheless, some symptoms that were found to be more associated with COVID-19, such as memory loss or anxiety, merit further investigation. These results should guide future follow-up of COVID-19 patients after hospital discharge.
Derivation and validation of urinary TIMP-1 for the prediction of acute kidney injury and mortality in critically ill children
Authors: Huang Hui , Lin Qiang , Dai Xiaomei , Chen Jiao , Bai Zhenjiang , Li Xiaozhong , Fang Fang , Li Yanhong
Published: February 2022

Background

Acute kidney injury (AKI) is associated with high morbidity and mortality. Multiple urinary biomarkers have been identified to be associated with the prediction of AKI and outcomes. However, the accuracy of these urinary biomarkers for AKI and associated outcomes has not been clearly defined, especially in heterogeneous populations. The aims of the study were to compare the ability of 10 existing or potential urinary biomarkers to predict AKI and pediatric intensive care unit (PICU) mortality and validate urinary tissue inhibitor of metalloproteinases-1 (uTIMP-1) as a better biomarker for early prediction in heterogeneous critically ill children.

Methods

A derivation-validation approach with separate critically ill cohorts was designed. We first conducted a prospective cohort study to determine the ability of 10 urinary biomarkers serially measured in 123 children during the first 7 days of PICU stay to predict AKI and PICU mortality (derivation study) and further validated the better biomarker of uTIMP-1 in a separate cohort of 357 critically ill children (validation study). AKI diagnosis was based on KDIGO classification with serum creatinine and urine output. PICU mortality was defined as all-cause mortality.

Results

In the derivation cohort, 17 of 123 (13.8%) children developed AKI stage 3 or died during the PICU stay, and both the initial and peak uTIMP-1 displayed the highest AUCs of 0.87 (0.79–0.94) and 0.90 (0.84–0.96), respectively, for predicting AKI stage 3 or death. In the validation cohort, 78 of 357 (21.8%) developed AKI during the first week after admission, and 38 (10.6%) died during the PICU stay. The initial uTIMP-1 level was validated to be independently associated with AKI (AOR = 2.88, 95% CI 1.97–4.21), severe AKI (AOR = 2.62, 95% CI 1.78–3.88), AKI stage 3 (AOR = 2.94, 95% CI 1.84–4.68) and PICU mortality (AOR = 1.92, 95% CI 1.11–3.30) after adjustment for potential confounders. The predictive values of uTIMP-1 for AKI, severe AKI, AKI stage 3 and PICU mortality were 0.80 (0.74–0.86), 0.83 (0.77–0.89), 0.84 (0.77–0.92) and 0.83 (0.76–0.89), respectively.

Conclusions

Urinary TIMP-1 levels have been identified and validated to be independently associated with AKI and PICU mortality in independent prospective cohorts and may be an early potential indicator of AKI and PICU mortality in critically ill children.
Neuronal FcεRIα directly mediates ocular itch via IgE-immune complex in a mouse model of allergic conjunctivitis
Authors: Cui Huan , Liu Fan , Fang Yehong , Wang Tao , Yuan Bo , Ma Chao
Published: February 2022

Background

Classical understanding of allergic conjunctivitis (ACJ) suggests that ocular itch results from a mast cell-dependent inflammatory process. However, treatments that target inflammatory mediators or immune cells are often unsatisfying in relieving the stubborn itch symptom. This suggests that additional mechanisms are responsible for ocular itch in ACJ. In this study, we aim to determine the role of neuronal FcεRIa in allergic ocular itch.

Methods

Calcium imaging was applied to observe the effect of IgE-immune complex in trigeminal neurons. GenomicFcεRIaknockout mice and adeno-associated virus (AAV) mediated sensory neuronFcεRIaknockdown mice were used in conjunction with behavioral tests to determine ocular itch. In addition, immunohistochemistry, Western blot and quantitative RT-PCR were used for in vitro experiments.

Results

We found that FcεRIα was expressed in a subpopulation of conjunctiva sensory neurons. IgE-IC directly activated trigeminal neurons and evoked acute ocular itch without detectible conjunctival inflammation. These effects were attenuated in both a globalFcεRIa-knockout mice and after sensory neuronal-specificFcεRIa-knockdown in the mouse trigeminal ganglion. In an ovalbumin (OVA) induced murine ACJ model, FcεRIα was found upregulated in conjunctiva-innervating CGRP+ sensory neurons. Sensory neuronal-specific knockdown ofFcεRIasignificantly alleviated ocular itch in the ACJ mice without affecting the immune cell infiltration and mast cell activation in conjunctiva. Although FcεRIα mRNA expression was not increased by IgE in dissociated trigeminal ganglion neurons, FcεRIα protein level was enhanced by IgE in a cycloheximide-resistance manner, with concordant enhancement of neuronal responses to IgE-IC. In addition, incremental sensitization gradually enhanced the expression of FcεRIα in small-sized trigeminal neurons and aggravated OVA induced ocular itch.

Conclusions

Our study demonstrates that FcεRIα in pruriceptive neurons directly mediates IgE-IC evoked itch and plays an important role in ocular itch in a mouse model of ACJ. These findings reveal another axis of neuroimmune interaction in allergic itch condition independent to the classical IgE-mast cell pathway, and might suggest novel therapeutic strategies for the treatment of pruritus in ACJ and other immune-related disorders.
Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter
Authors: Garcia-Bonilla Maria , Castaneyra-Ruiz Leandro , Zwick Sarah , Talcott Michael , Otun Ayodamola , Isaacs Albert M. , Morales Diego M. , Limbrick David D. , McAllister James P.
Published: February 2022

Background

Hydrocephalus is a neurological disease with an incidence of 80–125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants.

Methods

Hydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19–40 days, MRI scanning was performed to measure the ventricular volume. Stem cell proliferation was studied in the Subventricular Zone (SVZ), and cell death and oligodendrocytes were examined in the PVWM. The neuroinflammatory reaction was studied by quantifying astrocytes and microglial cells in the PVWM, and inflammatory cytokines in the CSF.

Results

The expansion of the ventricles was especially pronounced in the body of the lateral ventricle, where ependymal disruption occurred. PVWM showed a 44% increase in cell death and a 67% reduction of oligodendrocytes. In the SVZ, the number of proliferative cells and oligodendrocyte decreased by 75% and 57% respectively. The decrease of the SVZ area correlated significantly with ventricular volume increase. Neuroinflammation occurred in the hydrocephalic pigs with a significant increase of astrocytes and microglia in the PVWM, and high levels of inflammatory interleukins IL-6 and IL-8 in the CSF.

Conclusion

The induction of acquired hydrocephalus produced alterations in the PVWM, reduced cell proliferation in the SVZ, and neuroinflammation.
A multiple technology-based physical activity intervention for Latina adolescents in the USA: randomized controlled trial study protocol for Chicas Fuertes
Authors: Larsen Britta , Greenstadt Emily , Olesen Brittany , Osuna Lilliana , Godino Job , Marcus Bess , Dunsiger Shira , Meyer Dawn , Zive Michelle
Published: February 2022

Background

Latina adolescents in the USA report some of the lowest rates of physical activity of any demographic subgroup; this is paralleled by a markedly higher lifetime risk of obesity, type 2 diabetes, and other conditions related to inactivity. Despite this, to date, no fully powered clinical trials have tested physical activity interventions specifically for this population. High use of mobile technologies (including text messages, smartphone apps, and social media) suggests this could be an appropriate intervention channel, while also having potential for broad reach. This paper describes the protocol for Chicas Fuertes, a fully powered randomized trial of a mobile technology-based physical activity intervention for Latina adolescents.

Methods

We plan to recruit 200 Latina teens (age 13–18) in San Diego, CA, currently engaging in ≤ 150 min/week of moderate-to-vigorous physical activity (MVPA) to be assigned 1:1 to the intervention or control groups. Those randomly assigned to the intervention group receive a one-on-one goal setting session followed by 6 months of mobile technology-based intervention, including a personalized website, Fitbit activity tracker and app, individually tailored text messages based on Fitbit data, and daily intervention content on Instagram. Those randomized to the control group receive only a Fitbit activity tracker. The main outcome is change in weekly minutes of MVPA from baseline to 6 months, measured both objectively (ActiGraph accelerometers and Fitbit Inspire HR) and subjectively (7-Day Physical Activity Recall Interview). Additional outcomes are maintenance of activity change at 12 months and changes in psychosocial constructs, including social support and self-efficacy, engagement with mobile technology channels, and costs of intervention delivery. We are also examining the potential mediators and moderators of the intervention. The efficacy of the intervention is analyzed using a mixed effects regression model, adjusting for any potential confounders not balanced by randomization. All analyses of accelerometer measured MVPA are also adjusted for wear time.

Discussion

The Chicas Fuertes trial uses widely available mobile technologies to target critical health behavior, physical activity, in Latina teens, a population with a high lifetime risk of lifestyle-related diseases. The results will speak to the efficacy and acceptability of the intervention, which has the potential for broad dissemination.

Trial registration

ClinicalTrials.govNCT04190225. Registered on November 20, 2019
Synthesis, in vitro biological evaluation and molecular modelling of new 2-chloro-3-hydrazinopyrazine derivatives as potent acetylcholinesterase inhibitors‏ on PC12 cells
Authors: Taheri Maryam , Aslani Samira , Ghafouri Hossein , Mohammadi Asadollah , Akbary Moghaddam Vaha , Moradi Nastarn , Naeimi Hananeh
Published: February 2022

Background

The loss of cholinergic neurotransmission in Alzheimer's disease (AD) patients' brain is accompanied by a reduced concentration of Acetylcholine (ACh) within synaptic clefts. Thus, the use of acetylcholinesterase inhibitors (AChEIs) to block the cholinergic degradation of ACh is a promising approach for AD treatment. In the present study, a series of 2-chloro-3-hydrazinopyrazine derivatives (CHP1-5) were designed, synthesized, and biologically evaluated as potential multifunctional anti-AD agents.

Methods

In addition, the chemical structures and purity of the synthesized compounds were elucidated through using IR,1H and13C NMR, and elemental analyses. Further, the intended compounds were assessed in vitro for their AChE inhibitory and neuroprotective effects. Furthermore, DPPH, FRAP and ABTS assays were utilized to determine their antioxidant activity. The statistical analysis was performed using one-way ANOVA.

Results

Based on the results, CHP4 and CHP5 exhibited strong AChE inhibitory effects with the IC50 values of 3.76 and 4.2 µM compared to the donepezil (0.53 µM), respectively. The study examined the effect and molecular mechanism of CHP4 on the Ab1–42-induced cytotoxicity in differentiated PC12 cells. At concentrations of 0–100 μM, CHP4 was non-toxic in PC12. Additionally, Ab1–42 significantly stimulated tau hyperphosphorylation and induced differentiated PC12 cell death. Further, CHP4 resulted in diminishing the Ab1–42-induced toxicity in PC12 cell significantly. CHP4 at 30 μM concentration significantly increased the Ab1–42-induced HSP70 expression and decreased tau hyperphosphorylation.

Conclusions

According to the results of our studies CHP4 can be considered as safe and efficient AChEI and employed as a potential multifunctional anti-AD agent.
Liquid biopsy, using a novel DNA methylation signature, distinguishes pancreatic adenocarcinoma from benign pancreatic disease
Authors: Vrba Lukas , Futscher Bernard W. , Oshiro Marc , Watts George S. , Menashi Emmanuel , Hu Charles , Hammad Hytham , Pennington Daniel R. , Golconda Umamaheshwari , Gavini Hemanth , Roe Denise J. , Shroff Rachna T. , Nelson Mark A.
Published: February 2022

We tested the ability of a novel DNA methylation biomarker set to distinguish metastatic pancreatic cancer cases from benign pancreatic cyst patients and to monitor tumor dynamics using quantitative DNA methylation analysis of cell-free DNA (cfDNA) from blood samples. The biomarkers were able to distinguish malignant cases from benign disease with high sensitivity and specificity (AUC = 0.999). Furthermore, the biomarkers detected a consistent decline in tumor-derived cfDNA in samples from patients undergoing chemotherapy. The study indicates that our liquid biopsy assay could be useful for management of pancreatic cancer patients.
Attenuates of NAD+ impair BMSC osteogenesis and fracture repair through OXPHOS
Authors: Li Boer , Shi Yu , Liu Mengyu , Wu Fanzi , Hu Xuchen , Yu Fanyuan , Wang Chenglin , Ye Ling
Published: February 2022

Background

Controlling the adipo-osteogenic lineage commitment of bone marrow mesenchymal stem cell (BMSC) in favor of osteogenesis is considered a promising approach for bone regeneration and repair. Accumulating evidence indicates that oxidative phosphorylation (OXPHOS) is involved in regulating cell fate decisions. As an essential cofactor for OXPHOS, nicotinamide adenine dinucleotide (NAD) has been shown to correlate with the differentiation of stem cells. However, whether NAD manipulates BMSC lineage commitment through OXPHOS remains elusive. Therefore, it is critical to investigate the potential role of NAD on energy metabolism in mediating BMSC lineage commitment.

Methods

In this study, the mitochondrial respiration and intracellular NAD+ level were firstly compared between osteogenic and adipogenic cells. For validating the role of NAD in mitochondrial OXPHOS, the inhibitor of NAD+ salvage pathway FK866 and activator P7C3 were used to manipulate the NAD+ level during osteogenesis. Furthermore, a murine femur fracture model was established to evaluate the effect of FK866 on bone fracture repair.

Results

We elucidated that osteogenic committed BMSCs exhibited increased OXPHOS activity and a decreased glycolysis accompanied by an elevated intracellular NAD+ level. In contrast, adipogenic committed BMSCs showed little change in OXPHOS but an upregulated activity in glycolysis and a decline in intracellular NAD+ level in vitro. Moreover, attenuates of NAD+ via salvage pathway in BMSCs diminished osteogenic commitment due to mitochondria dysfunction and reduced activity of OXPHOS. The cells were rescued by supplementing with nicotinamide mononucleotide. In addition, treatment with NAD+ inhibitor FK866 impaired bone fracture healing in vivo.

Conclusion

Our data reveals NAD+-mediated mitochondrial OXPHOS is indispensable for osteogenic commitment in BMSCs and bone repair, which might provide a potential therapeutic target for bone repair and regeneration.
Transfer language space with similar domain adaptation: a case study with hepatocellular carcinoma
Authors: Tariq Amara , Kallas Omar , Balthazar Patricia , Lee Scott Jeffery , Desser Terry , Rubin Daniel , Gichoya Judy Wawira , Banerjee Imon
Published: February 2022

Background

Transfer learning is a common practice in image classification with deep learning where the available data is often limited for training a complex model with millions of parameters. However, transferring language models requires special attention since cross-domain vocabularies (e.g. between two different modalities MR and US) do not always overlap as the pixel intensity range overlaps mostly for images.

Method

We present a concept of similar domain adaptation where we transfer inter-institutional language models (context-dependent and context-independent) between two different modalities (ultrasound and MRI) to capture liver abnormalities.

Results

We use MR and US screening exam reports for hepatocellular carcinoma as the use-case and apply the transfer language space strategy to automatically label imaging exams with and without structured template with > 0.9 average f1-score.

Conclusion

We conclude that transfer learning along with fine-tuning the discriminative model is often more effective for performing shared targeted tasks than the training for a language space from scratch.
The characteristics of effective technology-enabled dementia education: a systematic review and mixed research synthesis
Authors: Muirhead Kevin , Macaden Leah , Smyth Keith , Chandler Colin , Clarke Charlotte , Polson Rob , O’Malley Chris
Published: February 2022

Background

Dementia education is required to address gaps in dementia-specific knowledge among health and social care practitioners amidst increasing dementia prevalence. Harnessing technology for dementia education may remove obstacles to traditional education and empower large communities of learners. This systematic review aimed to establish the technological and pedagogical characteristics associated with effective technology-enabled dementia education for health and social care practitioners.

Methods

MEDLINE, PubMed, Web of Science, CINAHL, Scopus, PsycINFO, ERIC and OVID Nursing Database were searched from January 2005 until February 2020. Quantitative, qualitative and mixed methods studies were eligible for inclusion. Study quality was assessed with the Mixed Methods Appraisal Tool. Quantitative evidence was categorised based on Kirkpatrick’s Model. Qualitative data was synthesised thematically and integrated with quantitative findings before conclusions were drawn.

Results

Twenty-one published papers were identified. Participants were acute, primary and long-term care practitioners, or were students in higher education. Most training was internet-based; CD-ROMs, simulations and tele-mentoring were also described. Technology-enabled dementia education was predominantly associated with positive effects on learning outcomes. Case-based instruction was the most frequently described instructional strategy and videos were common modes of information delivery. Qualitative themes emerged as existing strengths and experience; knowledge gaps and uncertainty; developing core competence and expertise; involving relevant others; and optimising feasibility.

Discussion

Technology-enabled dementia education is likely to improve dementia knowledge, skills and attitudes among health and social care practitioners from multiple practice contexts. Confidence in the results from quantitative studies was undermined by multiple confounding factors that may be difficult to control in the educational research context. Convenience and flexibility are key benefits of technology-enabled instructive and simulated pedagogy that can support the application of theory into practice. More research is required to understand the role of online learning networks and provisions for equitable engagement. A future emphasis on organisational and environmental factors may elucidate the role of technology in ameliorating obstacles to traditional dementia education.

Systematic review registration

PROSPERO (CRD42018115378)
Muon-catalyzed fusion and annihilation energy generation will supersede non-sustainable T + D nuclear fusion
Authors: Holmlid Leif
Published: February 2022

Background

Large-scale fusion reactors using hydrogen isotopes as fuel are under development at several places in the world. These types of fusion reactors use tritium as fuel for the T + D reaction. However, tritium is not a sustainable fuel, since it likely will require fission reactors for its production, and since it is a dangerous material due to its radioactivity with main risks of release to the environment during tritium production, transport and refuelling operations. Thus, widespread use of fusion relying on tritium fuel should be avoided. At least two better methods for producing the nuclear energy needed in the world indeed already exist, using deuterium or ordinary hydrogen as fuel, and more methods need to be developed. It should be noted that the first experiments with sustained laser-driven fusion above break-even using deuterium as fuel were published already in 2015. Similar results for T + D fusion do not exist even after 60 years of development, which gives no confidence in this approach.

Main text

The well-known muon-induced fusion (often called muon-catalyzedfusion) can use non-radioactive deuterium as fuel. With the recent development of a high intensity muon source (1013muons per laser shot) (patented), this method is technically and economically feasible today. Due to the low energy cost of producing muons at < 1 MeV with this new source, the length of the so-called catalytic chain is unimportant. This removes the 60-year-old enigma, concerning the so-called alpha sticking process. The recently developed annihilation energy generation uses ordinary hydrogen in the form of ultradense hydrogen H(0) as fuel and is thus sustainable and has very high efficiency.

Conclusions

Muon-induced fusion is able to directly replace most combustion-based power stations in the world, giving sustainable and environmentally harmless power (primarily heat), in this way eliminating most CO2emissions of human energy generation origin. Annihilation-based power generation has the potential to replace almost all other uses of fossil fuels within a few decades, also in mobile applications, including spaceflight, where it is the only method able to give relativistic rocket propulsion.
Prescriptions patterns and appropriateness of usage of antibiotics in non-teaching community hospitals in South Korea: a multicentre retrospective study
Authors: Kim Yong Chan , Park Ji Young , Kim Bongyoung , Kim Eu Suk , Ga Hyuk , Myung Rangmi , Park Se Yoon , Lee Myung Jin , Moon Song Mi , Park Sun Hee , Song Kyoung-Ho , Kim Hong Bin ,   Korea Study Group for Antimicrobial Stewardship (KOSGAP), Yang Jinwoo , Park Hyunok , Kang Ji Hoon , Yun Myoungsuk , Kim Young Taek , Lee Hye Jung , Hwang Woochang
Published: February 2022

Background

Although non-teaching community hospitals form the majority of healthcare providers in South Korea, there is limited data on antibiotic usage in them. To evaluate the pattern of antibiotic usage and its appropriateness in hospitals with < 400 beds in South Korea.

Methods

A multicentre retrospective study was conducted in 10 hospitals (six long-term care hospitals, three acute care hospitals, and one orthopaedic hospital), with < 400 beds in South Korea. We analysed patterns of antibiotic prescription in 2019, and their appropriateness in the participating hospitals. For the evaluation of the appropriateness of the prescription, 25 patients under antibiotic therapy were randomly selected at each hospital, over two separate periods. Due to the heterogeneity of their characteristics, the orthopaedics hospital was excluded from the analysis.

Results

The most commonly prescribed antibiotics in long-term care hospitals was fluoroquinolone, followed by beta-lactam/beta-lactamase inhibitor (anti-pseudomonal). In acute care hospitals, these were third generation cephalosporin, followed by first generation cephalosporin, and second generation cephalosporin. The major antibiotics that were prescribed in the orthopedics hospital was first generation cephalosporin Only 2.3% of the antibiotics were administered inappropriately. In comparison, 15.3% of patients were prescribed an inappropriate dose. The proportion of inappropriate antibiotic prescriptions was 30.6% of the total antibiotic prescriptions.

Conclusions

The antibiotic usage patterns vary between non-teaching community hospitals in South Korea. The proportion of inappropriate prescriptions exceeded 30% of the total antibiotic prescriptions.