bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Accuracy, Quality, and Readability of Online Patient Resources on Tarsal Coalition
Authors: Zhang Hui , Foster Brian , Graham Jove , Seeley Mark
Published: January 2022

Category:

Other; Hindfoot

Introduction/Purpose:

The internet is an inexpensive and convenient source for health information. However, without regulation, the quality and accuracy of the information is unknown. Tarsal coalition is a common cause of pediatric foot pain and disability. We hypothesized that the online patient information on tarsal coalition is of low accuracy, low quality, and of poor readability. Additionally, we hypothesized that sources found on the first search page were of higher quality, greater accuracy, and more readable.

Methods:

A cross-sectional review of the internet was performed using the term 'tarsal coalition' on the 3 most popular search engines. Unique sites were categorized based on authorship and search result order. Websites were evaluated using a novel content score based on the AAOS OrthoInfo site on tarsal coalition (max score: 20), JAMA Benchmark and DISCERN scores for quality, and Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE) for readability.

Results:

A total of 47 unique websites were evaluated. They ranged from professional organization/society websites to websites for individual practices and professional blogs. The average content score was 13.1 (range: 4-20). The average DISCRN score was 34.2 (range: 19-57.5). We did find a positive correlation between the content score and DISCERN scores of the included resources (p=0.04). The average 11.4 (range 8.5-15.5). Only 2 of the websites (4%) were written at or below an 8th grade reading level, which has been documented as the average reading level of the general population in the United States. Websites that were authored by physicians had greater DISCRN and readability scores compared to academic and private practice websites (DISCERN 40.4 vs 32.3 (p=0.001) and 31.7 (p=0.01), respectively, FKGL 13.0 vs 10.4 (p=0.002) and 11.1 (p=0.03), respectively, FRE 31.5 vs 48.7 (p=0.0001) and 45.2 (p=0.025), respectively).

Conclusion:

Online patient resources on tarsal coalition are of low quality, inaccurate, and too complex for the average reader. Physician authored websites may serve as better resources compared to academic or private practice sites. Physicians should caution patients using the internet for information on tarsal coalition.
The effect of select systemic medications on outcomes in diabetics with central retinal vein occlusion
Authors: Simmons Kirsten , Singh Pali , Borkar Durga S. , Birnbaum Faith , Thomas Akshay S. , Fekrat Sharon
Published: January 2022

Background:

Diabetes mellitus is a risk factor for central retinal vein occlusion (CRVO); however, it is unclear whether certain commonly used medications among diabetics or glycemic control impact visual outcomes in diabetic eyes with CRVO.

Purpose:

To evaluate the effect of select systemic medications and glycemic control on presenting features, treatment burden, and outcomes in patients with diabetes who develop a central retinal vein occlusion (CRVO).

Methods:

Retrospective longitudinal cohort study at a single tertiary academic referral center from 2009–2017 investigating eyes of patients being treated for diabetes mellitus at CRVO onset. Eyes with a prior history of anti-vascular endothelial growth factor (anti-VEGF) therapy or laser treatment within the year prior to CRVO onset were excluded. Main outcomes and measures were visual acuity (VA), central subfield thickness (CST), cystoid macular edema (CME), and number of intravitreal injections and laser treatment throughout follow-up.

Results:

We identified 138 eyes of 138 participants who were diabetic at CRVO onset. Of these, 49% had an ischemic CRVO. Median follow-up time was 25.5 months. Fifty-five eyes (40%) had a HbA1c within 6 months of CRVO presentation. HbA1c was positively correlated with both presenting CST ( p = 0.04) and presence of CME ( p < 0.01). In all 138 eyes, mean presenting VA was 20/246, and mean final VA was 20/364. Better-presenting VA was significantly associated with aspirin 325 mg use ( p = 0.04). Lower CST at presentation was significantly associated with metformin use ( p = 0.02). Sitagliptin use at CRVO onset was associated with a lower prevalence of CME at final follow-up ( p < 0.01). Lower final CST was significantly associated with glipizide use at CRVO onset ( p = 0.01). There were no significant associations between systemic medications or HbA1c and treatment burden or final VA ( p > 0.05).

Conclusion:

Although aspirin 325 mg, metformin, sitagliptin, and glipizide were associated with better-presenting VA, lower-presenting CST, lower prevalence of macular edema at final visit, and lower final CST, respectively, none of these systemic agents or glycemic control were associated with decreased treatment burden or improved visual outcomes in diabetics with CRVO.
Comprehensive overview of IRVAN syndrome: a structured review of Case Reports and Case Series
Authors: Khan Hashim Ali , Khan Qaim Ali , Shahzad Muhammad Aamir , Awan Muhammad Amer , Khan Naeemullah , Jahangir Smaha , Shaheen Fiza , Wali Kamran , Rodman Julie , Pizzimenti Jozeph , Saatci Ali Osman
Published: January 2022

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare spectrum of retinal vasculitis, aneurysms, and neuroretinitis affecting young individuals in their third decade. Most of our current knowledge is based on case reports, case series, and a handful of collaborative studies. There is much diversity in treatment approaches and outcomes in the reported literature. We have aggregated published case reports and case series into quantitative and narrative synthesis to draw evidence-based conclusions toward clinical features, atypical and rare findings, systemic associations, disease course, and treatment outcomes. The analysis suggested the disease mostly affects young individuals with a female predilection. Anterior chamber and vitreous inflammation are common than previously believed. The most prevalent pattern of retinal vasculitis in IRVAN eyes is mixed vasculitis, followed by arteritis and phlebitis. Most eyes at the time of presentation have capillary nonperfusion and require treatment. Most eyes retain good visual acuity; however, treatment is required to maintain visual function. Intravitreal antivascular endothelial growth factors administered as an adjunct to retinal laser photocoagulation are more likely to improve visual outcomes. Besides, we have discussed the different hypotheses on the etiopathogenesis of the disease and stronger evidence suggests an inflammatory origin of the disease.
Factors Associated with Interest in Complementary and Alternative Medicine Among Young Adult Survivors of Childhood Cancer
Authors: Baron Nelson Mary , Kim Yoonji , Hamilton Lauren , Dekker Anneke , Miller Kimberly , Hamilton Ann S. , Milam Joel
Published: January 2022

Background: Use of complementary and alternative medicine (CAM) by those undergoing cancer treatment is common. While some childhood cancer survivors (CCS) may use CAM to treat late effects, others may lack information about available alternative therapies. We sought to determine characteristics associated with seeking more information about CAM among an ethnically diverse sample of young adult CCS. Methods: Young adult CCS were selected from the population-based Los Angeles SEER cancer registry and surveyed at ages 18 to 39 as part of the Project Forward Cohort. Associations between demographic, clinical, and other factors with seeking information on CAM were examined with t-tests, Chi Square analyses, and logistic regression. Results: Among 1106 participants surveyed, 182 (18%) reported interest in obtaining more information on CAM. Interest in CAM was highest among males, older (vs. younger) participants, those born outside the U.S., those with a history of relapsed/recurrent or second cancers, those with greater depressive symptoms, and those with poorer self-rated health. Among Hispanic/Latino/Latinx respondents, depressive symptoms, birth outside the U.S., and higher Latino culture orientation was positively associated with CAM interest. Discussion: Depressive symptoms and unresolved health problems are associated with a need for information about alternative forms of therapy, particularly in those with born outside the U.S. Healthcare providers caring for CCS can incorporate appropriate CAM information to help address unmet physical and mental health needs.
Does Creative Arts Therapy Improve Distressing Symptoms in Children with Cancer? A Synthesis of Extant Literature
Authors: Raybin Jennifer L. , Harnke Ben , Hendricks-Ferguson Verna
Published: January 2022

Introduction: Children with cancer experience symptom distress which has been correlated with decreased quality of life (QOL). Creative arts therapy (CAT) encompasses the therapeutic use of creative arts which may improve QOL among children with cancer by affecting symptoms. Therefore, the research question was asked: Does CAT affect symptoms of pain, nausea, fatigue, anxiety, and mood in children with cancer? Methods: Based on the study question, a comprehensive literature search of PubMed, CINAHL, PsycINFO, and Embase was completed. Inclusion criteria limited articles to specific symptom outcomes in two-group intervention studies in the English language. Selected articles were confirmed for inclusion by the study team, followed by group discussion to develop matrices with levels of evidence based on the Grading of Recommendations Assessment, Development, and Evaluation (Grade) guidelines. Results: Initial searches revealed 1,391 articles, screened to 44 for systematic review. Based on the inclusion criteria, 11 articles remained. Four studies had evidence levels graded as low, three were low to moderate, and four were moderate. Outcomes of mood and anxiety were measured in five studies, pain in four, fatigue in two, and nausea in one study. Discussion: Psychological outcomes were measured more commonly than physical outcomes. Evidence reached a moderate grade in four studies. Summary: Through this synthesis of intervention studies with CAT in children with cancer, improvement in distressing symptoms has potential, but the state of the science for symptom management with CAT could be strengthened for nurses to promote CAT to improve QOL among children with cancer.
SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia
Authors: Brown Lauren M. , Hediyeh-zadeh Soroor , Sadras Teresa , Huckstep Hannah , Sandow Jarrod J. , Bartolo Ray C. , Kosasih Hansen J. , Davidson Nadia M. , Schmidt Breon , Bjelosevic Stefan , Johnstone Ricky , Webb Andrew I. , Khaw Seong L. , Oshlack Alicia , Davis Melissa J. , Ekert Paul G.
Published: January 2022

Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile resembling Philadelphia chromosome–positive ALL (Ph+ ALL) in the absence of BCR-ABL1. Tyrosine kinase–activating fusions, some involving ABL1, are recurrent drivers of Ph-like ALL and are targetable with tyrosine kinase inhibitors (TKIs). We identified a rare instance of SFPQ-ABL1 in a child with Ph-like ALL. SFPQ-ABL1 expressed in cytokine-dependent cell lines was sufficient to transform cells and these cells were sensitive to ABL1-targeting TKIs. In contrast to BCR-ABL1, SFPQ-ABL1 localized to the nuclear compartment and was a weaker driver of cellular proliferation. Phosphoproteomics analysis showed upregulation of cell cycle, DNA replication, and spliceosome pathways, and downregulation of signal transduction pathways, including ErbB, NF-κB, vascular endothelial growth factor (VEGF), and MAPK signaling in SFPQ-ABL1–expressing cells compared with BCR-ABL1–expressing cells. SFPQ-ABL1 expression did not activate phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling and was associated with phosphorylation of G2/M cell cycle proteins. SFPQ-ABL1 was sensitive to navitoclax and S-63845 and promotes cell survival by maintaining expression of Mcl-1 and Bcl-xL. SFPQ-ABL1 has functionally distinct mechanisms by which it drives ALL, including subcellular localization, proliferative capacity, and activation of cellular pathways. These findings highlight the role that fusion partners have in mediating the function of ABL1 fusions.
Inhibition of β-catenin signaling attenuates arteriovenous fistula thickening in mice by suppressing myofibroblasts
Authors: Liu Chung-Te , Hsu Shih-Chang , Hsieh Hui-Ling , Chen Cheng-Hsien , Chen Chun-You , Sue Yuh-Mou , Chen Tso-Hsiao , Hsu Yung-Ho , Lin Feng-Yen , Shih Chun-Ming , Shiu Yan-Ting , Huang Po-Hsun
Published: January 2022

Background

Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, β-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate β-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis.

Methods

Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF.

Results

Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell–cell adhesions, and the expression of the myofibroblast marker, integrin subunit β6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of β-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated β-catenin signaling. To confirm that β-catenin signaling contributes to AVF lesions, β-catenin signaling was inhibited with pyrvinium pamoate; β-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of β-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with β-catenin inhibition.

Conclusions

The results of this study indicate that mechanical disturbance in AVF activates β-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.
Prolonged migraine aura resembling ischemic stroke following CoronaVac vaccination: an extended case series
Authors: Suwanwela Nijasri C. , Kijpaisalratana Naruchorn , Tepmongkol Supatporn , Rattanawong Wanakorn , Vorasayan Pongpat , Charnnarong Chutibhorn , Tantivattana Jarturon , Roongruang Sirigunya , Ongphichetmetha Tatchaporn , Panjasriprakarn Poonnakarn , Chutinet Aurauma , Akarathanawat Wasan , Saver Jeffrey L.
Published: January 2022

Background

After the initiation of the COVID-19 vaccination program in Thailand, thousands of patients have experienced unusual focal neurological symptoms. We report 8 patients with focal neurological symptoms after receiving inactivated virus vaccine, CoronaVac.

Case series

Patients were aged 24–48 years and 75% were female. Acute onset of focal neurological symptoms occurred within the first 24 h after vaccination in 75% and between 1-7d in 25%. All presented with lateralized sensory deficits, motor deficits, or both, of 2–14 day duration. Migraine headache occurred in half of the patients. Magnetic resonance imaging of the brain during and after the attacks did not demonstrate any abnormalities suggesting ischemic stroke. All patients showed moderately large regions of hypoperfusion and concurrent smaller regions of hyperperfusion on SPECT imaging while symptomatic. None developed permanent deficits or structural brain injury.

Discussions

Here, we present a case series of transient focal neurological syndrome following Coronavac vaccination. The characteristic sensory symptoms, history of migraine, female predominant, and abnormal functional brain imaging without structural changes suggest migraine aura as pathophysiology. We propose that pain related to vaccine injection, component of vaccine, such as aluminum, or inflammation related to vaccination might trigger migraine aura in susceptible patients.
Effects of Random Nanosized TiN Grain on Characteristic of Gate-All-Around FinFETs with Ferroelectric HZO Layer
Authors: Li Yiming , Chuang Min-Hui , Tsai Yu-Chin
Published: January 2022

In this paper, we computationally study electrical characteristics for gate-all-around fin field effect transistors (GAA FinFETs) and negative capacitance GAA FinFETs (NC-GAA FinFETs) for sub-3-nm technological nodes. For the devices with the fin height of 55 nm, the on-state current increases (about 33% improvement) and the off-state current decreases (about 73% suppression) due to the NC effect. NC-GAA FinFETs have larger standard deviation of threshold voltage induced by the workfunction fluctuation (WKF) for both N-/P-type devices than those of GAA FinFETs. It is attributed to the variation of polarization in the different position of the ferroelectric layer. Notably, the inverter of NC-GAA FinFETs has larger noise margin and shorter delay time, compared with the inverter of GAA FinFETs; however, the characteristics of inverter of NC-GAA FinFETs suffer larger variability induced by the WKF.
Genome-scale analysis of genetic regulatory elements in Streptomyces avermitilis MA-4680 using transcript boundary information
Authors: Lee Yongjae , Lee Namil , Hwang Soonkyu , Kim Woori , Cho Suhyung , Palsson Bernhard O. , Cho Byung-Kwan
Published: January 2022

Background

The gram-positive bacterium, Streptomyces avermitilis, holds industrial importance as the producer of avermectin, a widely used anthelmintic agent, and a heterologous expression host of secondary metabolite-biosynthetic gene clusters. Despite its industrial importance, S. avermitilis’ genome organization and regulation of gene expression remain poorly understood. In this study, four different types of Next-Generation Sequencing techniques, including dRNA-Seq, Term-Seq, RNA-Seq and ribosome profiling, were applied to S. avermitilis to determine transcription units of S. avermitilis at a genome-wide level and elucidate regulatory elements for transcriptional and translational control of individual transcription units.

Result

By applying dRNA-Seq and Term-Seq to S. avermitilis MA-4680, a total of 2361 transcription start sites and 2017 transcript 3′-end positions were identified, respectively, leading to determination of 1601 transcription units encoded in S. avermitilis’ genome. Cataloguing the transcription units and integrated analysis of multiple high-throughput data types revealed the presence of diverse regulatory elements for gene expression, such as promoters, 5′-UTRs, terminators, 3′-UTRs and riboswitches. The conserved promoter motifs were identified from 2361 transcription start sites as 5′-TANNNT and 5′-BTGACN for the − 10 and − 35 elements, respectively. The − 35 element and spacer lengths between − 10 and − 35 elements were critical for transcriptional regulation of functionally distinct genes, suggesting the involvement of unique sigma factors. In addition, regulatory sequences recognized by antibiotic regulatory proteins were identified from the transcription start site information. Analysis of the 3′-end of RNA transcript revealed that stem structure formation is a major determinant for transcription termination of most transcription units.

Conclusions

The transcription unit architecture elucidated from the transcripts’ boundary information provides insights for unique genetic regulatory mechanisms of S. avermitilis. Our findings will elevate S. avermitilis’ potential as a production host for a diverse set of secondary metabolites.
Complete opioid transition to sublingual Buprenorphine after abdominal surgery is associated with significant reductions in opioid requirements, but not reduction in hospital length of stay: a retrospective cohort study
Authors: Heldreich Charlotte , Ganatra Sameer , Lim Zheng , Meyer Ilonka , Hu Raymond , Weinberg Laurence , Tan Chong O.
Published: January 2022

Background

The use of sublingual buprenorphine (SLBup) for acute pain after major abdominal surgery may offer the potential advantages of unique analgesic properties and more reliable absorption during resolving ileus. We hypothesized that complete opioid transition to SLBup rather than oral oxycodone (OOxy) in the early postoperative period after major abdominal surgery would reduce hospital length of stay, and acute pain and total OMEDD (Oral Morphine Equivalent Daily Dose) requirements in the first 24 h from post-parenteral opioid transition.

Methods

We reviewed 146 patients who had undergone elective and emergency abdominal surgery under our quaternary referral centre’s Upper Gastro-Intestinal and Colo-Rectal Surgical Units 6 months before and after the introduction of complete postoperative transition to sublingual buprenorphine, rather than oral oxycodone, in July 2017. Our primary endpoint was 24-hourly post-transition OMEDDs; secondary endpoints were 24-hourly post-transition Mean NRS-11 pain scores on movement (POM) and length of hospital stay (LOS). Univariate analysis and linear multivariate regression analyses were used to quantify effect size and identify surgical, patient & other analgesic factors associated with these outcome measures.

Results

Patients transitioning to SLBup had reduced 24-hourly post-transition OMEDD requirements on postoperative day 2 (POD) (26 mg less, p = 0.04) and NRS-11 POM at POD1 (0.7 NRS-11 units less, p = 0.01). When adjusting for patient, surgical and special analgesic factors, SLBup was associated with a similar reduction in OMEDDs (Unstandardised beta-coefficient -26 mg, p = 0.0001), but not NRS-11 POM (p = 0.47) or hospital LOS (p = 0.16).

Conclusions

Our change of practice from use of OOxy to SLBup as primary transition opioid from patient-controlled analgesia delivered full opioid agonists was associated with a clinically significant decrease in 24-hourly post-parenteral opioid transition OMEDDs and improved NRS-11 POM, but without an association with hospital LOS after major abdominal surgery. Further prospective randomized work is required to confirm these observed associations and impact on other important patient-centred outcomes.
Unfractionated heparin improves the clinical efficacy in adult sepsis patients: a systematic review and meta-analysis
Authors: Fu Sifeng , Yu Sihan , Wang Liang , Ma Xiaochun , Li Xu
Published: January 2022

Background

The anticoagulant treatment and clinical efficacy of heparin in sepsis remains controversial. We conducted a meta-analysis to estimate the clinical efficacy of unfractionated heparin (UFH) in adult septic patients.

Method

A systematic review of Medline, Cochrane Library, PubMed, Embase, WEIPU database, CNKI database, WANFANG database was performed from inception to January 2021. We included Randomized controlled trials (RCTs) and the main outcome was 28 d mortality. Data analysis was performed with Review Manager (RevMan) version 5.3 software. The meta-analysis included 2617 patients from 15 RCTs.

Results

Comparing to control group, UFH could reduce 28 d mortality (RR: 0.82; 95% CI: 0.72 to 0.94) especially for patient with Acute Physiology and Chronic Health Evaluation II (APACHE II) > 15, (RR: 0.83; 95% CI: 0.72 to 0.96). In UFH group, the platelet (PLT) (MD: 9.18; 95% CI: 0.68 to 17.68) was higher, the activated partial thromboplastin time (APTT) was shorter (MD: -8.01; 95% CI: − 13.84 to − 2.18) and the prothrombin time (PT) results (P > 0.05) failed to reach statistical significance. UFH decreased multiple organ dysfunction syndrome (MODS) incidence (RR: 0.61; 95% CI: 0.45 to 0.84), length of stay (LOS) in ICU (MD: -4.94; 95% CI: − 6.89 to − 2.99) and ventilation time (MD: -3.01; 95% CI: − 4.0 to − 2.02). And UFH had no adverse impact on bleeding (RR: 1.10; 95% CI: 0.54 to 2.23).

Conclusion

This meta-analysis suggests that UFH may reduce 28 d mortality and improve the clinical efficacy in sepsis patients without bleeding adverse effect.
A non-interventional cross-sectional re-contact study investigating the relationship between overactive bladder and frailty in older adults in Japan
Authors: Yoshida Masaki , Satake Shosuke , Ishida Kota , Tanaka Yusuke , Ukai Masashi
Published: January 2022

Background

Increasing age is associated with frailty and a higher prevalence of overactive bladder (OAB). Given the rapidly increasing proportion of older adults in Japan, a better understanding of the relationship between frailty and OAB is needed to inform future healthcare planning. This study assessed the association between frailty and OAB in older adults in Japan and evaluated the impact on their health-related quality of life (HRQoL).

Methods

This was a cross-sectional re-contact study of respondents who previously completed the National Health and Wellness Survey 2018 in Japan. Participants were aged ≥65 years and Japanese speakers and readers. As part of a customized online survey, participants were screened for frailty using the Kihon Checklist (frail = scores ≥8 points) and OAB using the overactive bladder symptom score (OAB = total score ≥ 3 points and ≥ 2 points on question 3). The primary endpoint was the odds ratio of frailty in older adults with and without OAB assessed using a multivariable logistic regression model. Secondary endpoints were the prevalence rates of OAB and frailty. Exploratory endpoints assessed HRQoL using the Medical Outcomes Study 12-Item Short Form Survey Instrument version 2 (SF-12v2).

Results

Overall, 2953 participants were included: 150 (5.1%) were frail OAB, 416 (14.1%) non-frail OAB, 287 (9.7%) frail non-OAB, and 2100 (71.1%) non-frail non-OAB. There was a statistically significant correlation between frailty and OAB demonstrated by an adjusted odds ratio (95% CI) of 2.78 (2.18–3.54; p <  0.001). The prevalence (95% CI) of OAB was 34.3% (29.9–38.8) in frail and 16.5% (15.1–18.0) in non-frail older adults; the prevalence of frailty was 26.5% (22.9–30.1) and 12.0% (10.7–13.3) in older adults with and without OAB. HRQoL was assessed in 150 participants per group. The adjusted HRQoL analyses showed significantly lower scores in participants who were frail OAB vs. frail non-OAB for most of the SF-12v2 scores/sub-component scores.

Conclusions

These data highlight the statistically significant positive correlation between frailty and OAB among older adults in Japan and may provide valuable information on the burden of OAB and frailty on older adults to healthcare professionals when considering future healthcare planning.
Nomogram predicting cesarean delivery undergoing induction of labor among high-risk nulliparous women at term: a retrospective study
Authors: Zhou Hang , Gu Ning , Yang Yan , Wang Zhiqun , Hu Yali , Dai Yimin
Published: January 2022

Background

Our aim was to create and validate a nomogram predicting cesarean delivery after induction of labor among nulliparous women at term.

Methods

Data were obtained from medical records from Nanjing Drum Tower Hospital. Nulliparous women with singleton pregnancies undergoing induction of labor at term were involved. A total of 2950 patients from Jan. 2014 to Dec. 2015 were served as derivation cohort. A nomogram was constructed by multivariate logistic regression using maternal, fetal and pregnancy characteristics. The predictive accuracy and discriminative ability of the nomogram were internal validated by 1000-bootstrap resampling, followed by external validation of a new dataset from Jan. 2016 to Dec. 2016.

Results

Logistic regression revealed nine predictors of cesarean delivery, including maternal height, age, uterine height, abdominal circumference, estimated fetal weight, indications for induction of labor, initial cervical consistency, cervical effacement and station. Nomogram was well calibrated and had an AUC of 0.73 (95% confidence interval [CI], 0.70-0.75) after bootstrap resampling for internal validation. The AUC in external validation reached 0.67, which was significantly higher than that of three models published previously (P<0.05).

Conclusions

This validated nomogram, constructed by variables that were obtained form medical records, can help estimate risk of cesarean delivery before induction of labor.
Variant analysis of 92 Chinese Han families with hearing loss
Authors: Jin Xiaohua , Huang Shasha , An Lisha , Zhang Chuan , Dai Pu , Gao Huafang , Ma Xu
Published: January 2022

Background

Hearing loss (HL) is the most frequent sensory deficit in humans, HL has strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counseling for the patient’s family.

Methods

We undertook pedigree analysis in 92 Chinese non-syndromic HL patients by targeted next-generation sequencing and Sanger sequencing.

Results

Among the 92 HL patients, 18 were assigned a molecular diagnosis with 33 different variants in 14 deafness genes. Eighteen of the variants in 12 deafness genes were novel. Variants in TMC1, CDH23, LOXHD1 and USH2A were each detected in two probands, and variants in POU3F4, OTOA, GPR98, GJB6, TRIOBP, SLC26A4, MYO15A, TNC, STRC and TMPRSS3 were each detected in one proband.

Conclusion

Our findings expand the spectrum of deafness gene variation, which will inform genetic diagnosis of deafness and add to the theoretical basis for the prevention of deafness.
Stimuli-responsive DNA-based hydrogels for biosensing applications
Authors: Chen Mengmeng , Wang Yu , Zhang Jingyang , Peng Yuan , Li Shuang , Han Dianpeng , Ren Shuyue , Qin Kang , Li Sen , Gao Zhixian
Published: January 2022

The base sequences of DNA are endowed with the rich structural and functional information and are available for the precise construction of the 2D and 3D macro products. The hydrogels formed by DNA are biocompatible, stable, tunable and biologically versatile, thus, these have a wide range of promising applications in bioanalysis and biomedicine. In particular, the stimuli-responsive DNA hydrogels (smart DNA hydrogels), which exhibit a reversible and switchable hydrogel to sol transition under different triggers, have emerged as smart materials for sensing. Thus far, the combination of the stimuli-responsive DNA hydrogels and multiple sensing platforms is considered as biocompatible and is useful as the flexible recognition components. A review of the stimuli-responsive DNA hydrogels and their biosensing applications has been presented in this study. The synthesis methods to prepare the DNA hydrogels have been introduced. Subsequently, the current status of the stimuli-responsive DNA hydrogels in biosensing has been described. The analytical mechanisms are further elaborated by the combination of the stimuli-responsive DNA hydrogels with the optical, electrochemical, point-of-care testing (POCT) and other detection platforms. In addition, the prospects of the application of the stimuli-responsive DNA hydrogels in biosensing are presented.

Graphical abstract
Effectiveness of community health workers on identification and mobilization of persons living with epilepsy in rural Rwanda using a validated screening tool
Authors: Sebera Fidele , Dedeken Peter , Kayirangwa Jeannine , Umwiringirwa Josiane , Kajeneza Delphine , dos Reis Nicole Alves , Leers Tim , Teuwen Dirk E. , Boon Paul A. J. M.
Published: January 2022

Introduction

Engagement and training of community health workers (CHWs) have demonstrated their value in different conditions. Despite repeat epilepsy trainings of CHWs in Northern Rwanda, the treatment gap remained high. We hypothesized that effectiveness of CHWs on mobilization of patients living with epilepsy (PwE) could be improved using a validated tool for epilepsy screening.

Methods

CHWs associated with health centers (HCs) of Gataraga, Kimonyi and Karwasa attended a 1-day training on epilepsy and Limoges epilepsy screening questionnaire (Kinyarwanda version). Thereafter, CHWs screened households in their villages for persons with one or more positive answer. CHWs then accompanied positively screened persons to a consultation for clinical evaluation and diagnosis by neurologists, and demographic data were collected. CHW variables were collected retrospectively.

Results

A total of 1308 persons were screened positive by 281 CHWs. Clinical diagnosis of epilepsy was confirmed in 589 and in 93 additional unscreened PwE, presenting voluntarily at the consultation. Pre-intervention number of 48 PwE increased to 682 after, a 14.2-fold increase. The overall treatment gap amounted to 93.0%. The age distribution of male PwE preponderance at younger age inverted to females at older age.

CHW characteristics showed non-significant differences within and across HCs. Logistic regression did not relate CHW age, gender, and experience to screening results.

Discussion

Equipping CHWs with a validated screening tool was effective in identifying and mobilizing PwE in a short time frame and offers opportunity for future scaling. Nonetheless, barriers to sustainability of care will need to be addressed before.
Perceptions of peer contraceptive use and its influence on contraceptive method use and choice among young women and men in Kenya: a quantitative cross-sectional study
Authors: Calhoun Lisa M. , Mirzoyants Anastasia , Thuku Sylvia , Benova Lenka , Delvaux Therese , van den Akker Thomas , McGuire Courtney , Onyango Bernard , Speizer Ilene S.
Published: January 2022

Background

Prior research has established that an individual’s social environment may influence his or her reproductive behaviors, yet less is known about peer influence on contraceptive use among young people (ages 15–24). In Kenya, the site of this study, 15% of adolescents ages 15–19 have begun childbearing and 45% of sexually active young women report current use of a modern contraceptive method. This highlights the need to better understand what factors influence young people to use contraception. The objective of this study is to explore the relationship between the perception of peers’ use of contraceptives and contraceptive use and method choice among young men and women in Kenya.

Methods

This study utilizes a nationally representative sample of women and men aged 15–24 years from the 2018 and 2019 cross sectional Shujaaz State of the Kenyan Youth annual surveys. Among the sample of sexually experienced young people (59%), multivariable multinomial logistic regression was used to explore the association between the perception of peers’ use of contraceptives and the respondent’s contraceptive method choice: non-user, condom use or use of any other modern method. Results are presented separately for young men and young women.

Results

Our results show that sexually experienced young men and women who perceive that their peers are using contraceptives are more likely to report current use of condoms compared to being a nonuser (RRR = 2.12, p < 0.001, RRR = 2.59, p < 0.001, respectively); they are also more likely to use condoms than another modern method of contraception (RRR = 2.13, p = 0.034, RRR = 1.71, p = 0.014, respectively). Young women are more likely to use another modern method (not including condoms) than be a nonuser when they perceive that their peers’ use contraceptives (RRR = 1.51, p = 0.020).

Conclusions

The results of this study highlight the important role of peer influence on young people’s contraceptive choices. These findings can be used to develop programs that encourage behavior change communication activities in Kenya that focus on normalizing use of a full range of contraceptive methods among peer groups of sexually experienced young people.
Bladder cancer and human papillomavirus association: a systematic review and meta-analysis
Authors: Khatami Alireza , Salavatiha Zahra , Razizadeh Mohammad Hossein
Published: January 2022

Background

The possible association of human papillomavirus (HPV) and bladder cancer has been controversial. Older findings suggest a significant association between the virus and bladder cancer. The aim of this study was to evaluate the data from the last ten years to estimate the prevalence of the virus in bladder cancer patients and to assess the association between the virus and cancer.

Method

A search of major databases was conducted to retrieve published English language studies between January 2011 and March 2021. In the present study overall prevalence of the virus in bladder cancer patients was estimated along with the prevalence of subgroups. Also, the possible associations between the prevalence of the virus and bladder cancer and the possible impact of variables in the geographical area and the type of sample were measured by comprehensive meta-analysis software (V2.2, BIOSTAT).

Results

Unlike previous studies, despite the relatively high prevalence of the virus [pooled prevalence: 14.3% (95% CI 8.9–22.2%)] no significant association was found between HPV and bladder cancer (OR 2.077, 95% CI 0.940–4.587). No significant association was found between geographical area (except Asia) and type of sample with bladder cancer.

Conclusions

Given the significant prevalence, despite the insignificance of the association between virus and cancer, it seems that more studies with case–control design are needed to elucidate this association.
Identification of key gene signatures for the overall survival of ovarian cancer
Authors: Pawar Akash , Chowdhury Oindrila Roy , Chauhan Ruby , Talole Sanjay , Bhattacharjee Atanu
Published: January 2022

Background

The five-year overall survival (OS) of advanced-stage ovarian cancer remains nearly 25-35%, although several treatment strategies have evolved to get better outcomes. A considerable amount of heterogeneity and complexity has been seen in ovarian cancer. This study aimed to establish gene signatures that can be used in better prognosis through risk prediction outcome for the survival of ovarian cancer patients. Different studies’ heterogeneity into a single platform is presented to explore the penetrating genes for poor or better survival. The integrative analysis of multiple data sets was done to determine the genes that influence poor or better survival. A total of 6 independent data sets was considered. The Cox Proportional Hazard model was used to obtain significant genes that had an impact on ovarian cancer patients. The gene signatures were prepared by splitting the over-expressed and under-expressed genes parallelly by the variable selection technique. The data visualisation techniques were prepared to predict the overall survival, and it could support the therapeutic regime.

Results

We preferred to select 20 genes in each data set as upregulated and downregulated. Irrespective of the selection of multiple genes, not even a single gene was found common among data sets for the survival of ovarian cancer patients. However, the same analytical approach adopted. The chord plot was presented to make a comprehensive understanding of the outcome.

Conclusions

This study helps us to understand the results obtained from different studies. It shows the impact of the heterogeneity from one study to another. It shows the requirement of integrated studies to make a holistic view of the gene signature for ovarian cancer survival.
Pregnancy after breast cancer in BRCA1/2 mutation carriers
Authors: Maksimenko Jelena , Irmejs Arvīds , Gardovskis Jānis
Published: January 2022

Background

Often young women affected with BRCA1/2 positive breast cancer have not finished or even not started their childbearing before the onset of the disease. The aim of our mini-review is to summarize state of art knowledge on pregnancy after breast cancer in BRCA1/2 carriers.

Methods

A broad review of the literature was conducted using MEDLINE (via PubMed) for relevant articles published.

Main body of the abstract

This review summarizes the impact of different cytotoxic agents on a fertility, fertility preservation, maternal and fetal prognosis after pregnancy in breast cancer survivors with BRCA1/2.

Conclusion

According to the existing literature evidence pregnancy after therapy for breast cancer in BRCA carriers is safe for the mother and offspring, but patients’ needs, oncofertility counseling and fertility-sparing strategy should be carefully planned before starting the cytotoxic treatment.
Effects of paternal exposure to cigarette smoke on sperm DNA methylation and long-term metabolic syndrome in offspring
Authors: Liu Yunyun , Chen Shengzhu , Pang Dejian , Zhou Jiayi , Xu Xiuting , Yang Si , Huang Zhaofeng , Yu Bolan
Published: January 2022

Background

Although paternal exposure to cigarette smoke may contribute to obesity and metabolic syndrome in offspring, the underlying mechanisms remain uncertain.

Methods

In the present study, we analyzed the sperm DNA-methylation profiles in tobacco-smoking normozoospermic (SN) men, non-tobacco-smoking normozoospermic (N) men, and non-smoking oligoasthenozoospermic (OA) men. Using a mouse model, we also analyzed global methylation and differentially methylated regions (DMRs) of the DLK1 gene in paternal spermatozoa and the livers of progeny. In addition, we quantified DLK1 expression, executed an intra-peritoneal glucose tolerance test (IPGTT), measured serum metabolites, and analyzed liver lipid accumulation in the F1 offspring.

Results

Global sperm DNA-methylation levels were significantly elevated (p  < 0.05) in the SN group, and the methylation patterns were different among N, SN, and OA groups. Importantly, the methylation level of the DLK1 locus (cg11193865) was significantly elevated in the SN group compared to both N and OA groups (p  < 0.001). In the mouse model, the group exposed to cigarette smoke extract (CSE) exhibited a significantly higher global methylation DNA level in spermatozoa (p  < 0.001) and on the DMR sites of Dlk1 in 10-week-old male offspring (p  < 0.05), with a significant increase in Dlk1 expression in their livers (p  < 0.001). In addition, IPGTT and LDL levels were significantly altered (p  < 0.001), with elevated liver fat accumulation (p  < 0.05) in F1 offspring.

Conclusion

Paternal exposure to cigarette smoke led to increased global methylation of sperm DNA and alterations to the DMR of the DLK1 gene in the F1 generation, which may be inherited parentally and may perturb long-term metabolic function.
Leptin promoter methylation in female patients with painful multisomatoform disorder and chronic widespread pain
Authors: Achenbach Johannes , Rhein Mathias , Glahn Alexander , Frieling Helge , Karst Matthias
Published: January 2022

Background

Different functional somatic syndromes (FSS), fibromyalgia (FMS) and other unexplained painful conditions share many common clinical traits and are characterized by troubling and functionally disabling somatic symptoms. Chronic pain is most frequently reported and at the center of patients’ level of disease burden. The construct of multisomatoform disorder (MSD) allows to subsume severely impaired patients suffering from FSS, FMS and other unexplained painful conditions to be examined for common underlying processes. Altered leptin levels and a pathological response of the HPA-axis as a result of chronic stress and childhood trauma have been suggested as one of the driving factors of disease development and severity. Previous studies have demonstrated that methylation of the leptin promoter can play a regulatory role in addiction. In this study, we hypothesized that methylation of the leptin promoter is influenced by the degree of childhood traumatization and differs between patients with MSD and controls. A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using clinical and psychometric assessment while methylation level analysis of the leptin promoter was performed using DNA isolated from whole blood.

Results

In female controls, we found CpG C-167 to be negatively correlated with leptin levels, whereas in female patients CpG C-289, C-255, C-193, C-167 and methylation cluster (C-291 to C-167) at putative bindings sites for transcription factors Sp1 and c/EBPalpha were negatively correlated with leptin levels. Methylation levels were significantly lower in female patients CpG C-289 compared with controls. When looking at female patients with chronic widespread pain methylation levels were significantly lower at CpG C-289, C-255 and methylation cluster (C-291 to C-167).

Conclusion

Our findings support the hypothesis that epigenetic regulation of leptin plays a role in the regulation of leptin levels in patients with MSD. This effect is more pronounced in patients with chronic widespread pain.
A novel D-amino acid peptide with therapeutic potential (ISAD1) inhibits aggregation of neurotoxic disease-relevant mutant Tau and prevents Tau toxicity in vitro
Authors: Aillaud Isabelle , Kaniyappan Senthilvelrajan , Chandupatla Ram Reddy , Ramirez Lisa Marie , Alkhashrom Sewar , Eichler Jutta , Horn Anselm H. C. , Zweckstetter Markus , Mandelkow Eckhard , Sticht Heinrich , Funke Susanne Aileen
Published: January 2022

Background

Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder that mainly affects older adults. One of the pathological hallmarks of AD is abnormally aggregated Tau protein that forms fibrillar deposits in the brain. In AD, Tau pathology correlates strongly with clinical symptoms, cognitive dysfunction, and neuronal death.

Methods

We aimed to develop novel therapeutic D-amino acid peptides as Tau fibrillization inhibitors. It has been previously demonstrated that D-amino acid peptides are protease stable and less immunogenic than L-peptides, and these characteristics may render them suitable for in vivo applications. Using a phage display procedure against wild type full-length Tau (TauFL), we selected a novel Tau binding L-peptide and synthesized its D-amino acid version ISAD1 and its retro inversed form, ISAD1rev, respectively.

Results

While ISAD1rev inhibited Tau aggregation only moderately, ISAD1 bound to Tau in the aggregation-prone PHF6 region and inhibited fibrillization of TauFL, disease-associated mutant full-length Tau (TauFLΔK, TauFL-A152T, TauFL-P301L), and pro-aggregant repeat domain Tau mutant (TauRDΔK). ISAD1 and ISAD1rev induced the formation of large high molecular weight TauFL and TauRDΔK oligomers that lack proper Thioflavin-positive β-sheet conformation even at lower concentrations. In silico modeling of ISAD1 Tau interaction at the PHF6 site revealed a binding mode similar to those known for other PHF6 binding peptides. Cell culture experiments demonstrated that ISAD1 and its inverse form are taken up by N2a-TauRDΔK cells efficiently and prevent cytotoxicity of externally added Tau fibrils as well as of internally expressed TauRDΔK.

Conclusions

ISAD1 and related peptides may be suitable for therapy development of AD by promoting off-pathway assembly of Tau, thus preventing its toxicity.
Acquired pulmonary arteriovenous malformation associated with bronchiectasis: a case report
Authors: Kawasaki Yasutaka , Nojiri Masafumi , Oikawa Taku , Nishiki Kazuaki , Nakase Keisuke , Takahara Yutaka , Mizuno Shiro
Published: January 2022

Background

Pulmonary arteriovenous malformations are mostly caused by congenitally abnormal shunts between pulmonary arteries and pulmonary veins.

Case presentation

A 74-year-old Japanese woman with a history of bronchiectasis was admitted to our hospital because of dyspnea on exertion. Pulmonary angiography and reconstructed three-dimensional contrast-enhanced computed tomography images showed shunts between pulmonary arteries and pulmonary veins, indicating a diagnosis of pulmonary arteriovenous malformations. Coil embolization of the shunts was successful.

Conclusions

Our findings imply that bronchiectasis can cause pulmonary arteriovenous malformations, and thus patients who present with hypoxemia with bronchiectasis should be carefully evaluated.