bluuebunny/crossref_metadata_2025 huggingface dataset:
The authenticity of music culture of Kampung Naga and Cikondang Indigenous people, West Java, Indonesia
Authors: Gunara Sandie , Setiawan Susanto Toni , Cipta Febbry
Published: March 2022

The Indigenous knowledge of the Kampung Naga and Cikondang holds cultural understanding that has evolved as a result of interactions with their environment. This study aims to explain this awareness in terms of preserving the quality of traditional music —terebang sejak and beluk. Ethnography study, observations, documentation, audio-visual recordings, and in-depth interviews with terebang sejak and beluk musicians were conducted. The study reveals that their music authenticity is preserved through the influence of elders producing and transmitting Indigenous knowledge. This knowledge is in the form of traditional rules and local wisdom values passed down by their ancestors through their way of life. The findings also show that by maintaining their music authenticity, the Indigenous people of Kampung Naga and Cikondang earn more about their local culture which helps them preserve and perpetuate their cultural authenticity and Indigenous heritage.
Mask mandates for children during the COVID-19 pandemic: an international human rights perspective
Authors: Thomson Stephen
Published: March 2022

Epidemiological and physical safety issues form the core of the debate on whether children should be mandated to wear face masks during the COVID-19 pandemic. Largely absent from this debate are the crucial implications of international human rights law. Although the World Health Organization and the United Nations Children’s Fund have different mask-wearing recommendations for children aged 0–5 years, 6–11 years, and 12+ years, the UN Convention on the Rights of the Child applies to children of all ages. Children’s human rights under the UN Convention on the Rights of the Child and other treaties require decision makers to tread particularly carefully when deciding whether to mandate mask-wearing for children. Special consideration must be given to the potential for any detrimental impact of mask-wearing on children’s physical, psychological and psychosocial health and wellbeing. Other non-pharmaceutical interventions for children, such as physical distancing, good hand hygiene and improved indoor ventilation do not engage the legal complexities of mask-wearing and are a safer policy option for reducing SARS-CoV-2 transmission.
In a hub-and-spoke network, spoke-administered thrombolysis reduces mechanical thrombectomy procedure time and number of passes
Authors: Kraft Andrew W , Awad Amine , Rosenthal Joseph A , Dmytriw Adam A , Vranic Justin E , Bonkhoff Anna K , Bretzner Martin , Hirsch Joshua A , Rabinov James D , Stapleton Christopher J , Schwamm Lee H , Rost Natalia S , Leslie-Mazwi Thabele M , Patel Aman B , Regenhardt Robert W
Published: March 2022

Background

The utility of intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) in large vessel occlusion stroke (LVO) is controversial. Some data suggest IVT increases MT technical difficulty. Within our hub-and-spoke telestroke network, we examined how spoke-administered IVT affected hub MT procedure time and pass number.

Methods

Patients presenting to 25 spoke hospitals who were transferred to the hub and underwent MT from 2018 to 2020 were identified from a prospectively maintained database. MT procedure time, fluoroscopy time, and pass number were obtained from operative reports.

Results

Of 107 patients, 48 received IVT at spokes. Baseline characteristics and NIHSS were similar. The last known well (LKW)-to-puncture time was shorter among IVT patients (4.3 ± 1.9 h vs. 10.5 ± 6.5 h, p < 0.0001). In patients that received IVT, mean MT procedure time was decreased by 18.8 min (50.5 ± 29.4 vs. 69.3 ± 46.7 min, p = 0.02) and mean fluoroscopy time was decreased by 11.3 min (21.7 ± 15.8 vs. 33.0 ± 30.9 min, p = 0.03). Furthermore, IVT-treated patients required fewer MT passes (median 1 pass [IQR 1.0, 1.80] vs. 2 passes [1.0, 2.3], p = 0.0002) and were more likely to achieve reperfusion in ≤2 passes (81.3% vs. 59.3%, p = 0.01). An increased proportion of IVT-treated patients achieved TICI 2b-3 reperfusion after MT (93.9% vs. 83.8%, p = 0.045). There were no associations between MT procedural characteristics and LKW-to-puncture time.

Conclusion

Within our network, hub MT following spoke-administered IVT was faster, required fewer passes, and achieved improved reperfusion. This suggests spoke-administered IVT does not impair MT, but instead may enhance it.
False-positive detection of IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies in patients with rheumatoid arthritis: Possible effects of IgM or IgG rheumatoid factors on immunochromatographic assay results
Authors: Oka Shomi , Higuchi Takashi , Furukawa Hiroshi , Shimada Kota , Hashimoto Atsushi , Matsui Toshihiro , Tohma Shigeto
Published: March 2022

Objectives:

The severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019. A serological test is conducted to determine prior infection by severe acute respiratory syndrome coronavirus 2. We investigated whether the results of anti-severe acute respiratory syndrome coronavirus 2 antibody tests are modified in patients with rheumatoid arthritis.

Methods:

Patients in Japan with rheumatoid arthritis were recruited at Sagamihara Hospital from July 2014 to October 2015 ( n = 38; 2014 cohort) and at Tokyo Hospital from June to October 2020 ( n = 93; 2020 cohort). Anti-severe acute respiratory syndrome coronavirus 2 antibodies were measured by electrochemiluminescence immunoassay or immunochromatographic assay.

Results:

Anti-severe acute respiratory syndrome coronavirus 2 antibodies were not detected in any of the samples from rheumatoid arthritis patients tested by electrochemiluminescence immunoassay. Anti-severe acute respiratory syndrome coronavirus 2 antibodies were detected by immunochromatographic assay in the 3 (7.9%) serum samples in the 2014 cohort and 15 (16.1%) serum samples in the 2020 cohort. The IgM rheumatoid factor levels were increased in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (mean ± standard deviation (IU/ml), 1223.0 ± 1308.7 versus 503.6 ± 1947.2; P = 0.0101). The levels of IgG rheumatoid factor were also upregulated in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (4.0 ± 0.7 versus 2.4 ± 0.9; P = 0.0013).

Conclusion:

The results of IgM anti-severe acute respiratory syndrome coronavirus 2 antibody testing by immunochromatographic assay are modified by IgM or IgG rheumatoid factors in rheumatoid arthritis patients.
The Games People Play: A Psychological Analysis of Dalit Victimization in Ozhivudivasathe Kali
Authors: Miranda Mary Sapna Peter
Published: March 2022

Ozhivudivasathe Kali is a 2003 Malayalam short story written by Unni R. which shot into limelight with the release of the Kerala State Award winning film with the same title by Sanal K. Sasidharan. As the title suggests, the story recounts an ‘off-day game’ played by four middle-aged men in a dingy lodge. The drunken revelry soon turns into a cruel game exposing the fissures that exist under the guise of equality and acceptance. It echoes Golding’s Lord of the Flies and is a scathing and unsettling expose of the Kerala mindscape where Dalits still continue to be considered less human. A deadly game where the victim is ruthlessly hounded and finally killed for his ‘fault’ of being different, the story is arresting for its foreboding tone, given the way reality is shaping out all over the world these days where being the ‘other’ is an invitation to harassment and even decimation.
State-of-the-art review of lung imaging in cystic fibrosis with recommendations for pulmonologists and radiologists from the “iMAging managEment of cySTic fibROsis” (MAESTRO) consortium
Authors: Ciet Pierluigi , Bertolo Silvia , Ros Mirco , Casciaro Rosaria , Cipolli Marco , Colagrande Stefano , Costa Stefano , Galici Valeria , Gramegna Andrea , Lanza Cecilia , Lucca Francesca , Macconi Letizia , Majo Fabio , Paciaroni Antonella , Parisi Giuseppe Fabio , Rizzo Francesca , Salamone Ignazio , Santangelo Teresa , Scudeller Luigia , Saba Luca , Tomà Paolo , Morana Giovanni
Published: March 2022

Objective

Imaging represents an important noninvasive means to assess cystic fibrosis (CF) lung disease, which remains the main cause of morbidity and mortality in CF patients. While the development of new imaging techniques has revolutionised clinical practice, advances have posed diagnostic and monitoring challenges. The authors aim to summarise these challenges and make evidence-based recommendations regarding imaging assessment for both clinicians and radiologists.

Study design

A committee of 21 experts in CF from the 10 largest specialist centres in Italy was convened, including a radiologist and a pulmonologist from each centre, with the overall aim of developing clear and actionable recommendations for lung imaging in CF. Ana priorithreshold of at least 80% of the votes was required for acceptance of each statement of recommendation.

Results

After a systematic review of the relevant literature, the committee convened to evaluate 167 articles. Following five RAND conferences, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 28 main statements.

Conclusions

There is a need for international guidelines regarding the appropriate timing and selection of imaging modality for patients with CF lung disease; timing and selection depends upon the clinical scenario, the patient's age, lung function and type of treatment. Despite its ubiquity, the use of the chest radiograph remains controversial. Both computed tomography and magnetic resonance imaging should be routinely used to monitor CF lung disease. Future studies should focus on imaging protocol harmonisation both for computed tomography and for magnetic resonance imaging. The introduction of artificial intelligence imaging analysis may further revolutionise clinical practice by providing fast and reliable quantitative outcomes to assess disease status. To date, there is no evidence supporting the use of lung ultrasound to monitor CF lung disease.
E-cigarettes and nicotine abstinence: a meta-analysis of randomised controlled trials
Authors: Hanewinkel Reiner , Niederberger Kathrin , Pedersen Anya , Unger Jennifer B. , Galimov Artur
Published: March 2022

Objectives

To determine the effects of electronic cigarettes (e-cigarettes) as a therapeutic intervention compared to nicotine replacement therapy (NRT) on nicotine abstinence.

Methods

Two authors independently searched the PubMed, Embase, PsycInfo and Cochrane Central Register of Controlled Trials databases for articles published up to and including 10 July 2021. We included randomised controlled trials (RCTs) in which nicotine e-cigarettes were compared to NRT among current cigarette users. The primary outcome was abstaining from all nicotine-delivery devices. Secondary outcomes were 1) allocated product use (e-cigarettes or NRT) among successful cigarette quitters and 2) quitting cigarettes at the end of the trial using fixed-effect Mantel–Haenszel models.

Results

We included four RCTs representing 1598 adult participants (51.0% females). The mean age of participants in these studies ranged from 41 to 54 years, while average baseline smoking ranged from 14 to 21 cigarettes per day. Compared to NRT, e-cigarette use was associated with lower nicotine abstinence rates at the longest follow-up (risk ratio 0.50 (95% CI 0.32–0.77)). Among successful cigarette quitters, the risk of allocated product use by the end of the observational time was higher for e-cigarette users compared to NRT (risk ratio 8.94 (95% CI 3.98–20.07)). E-cigarette users had higher cigarette smoking cessation rates compared to NRT users (risk ratio 1.58 (95% CI 1.20–2.08)).

Conclusions

The use of e-cigarettes as a therapeutic intervention for smoking cessation may lead to permanent nicotine dependence.
Facilitators and barriers of preconception care in women with inflammatory bowel disease and rheumatic diseases: an explorative survey study in a secondary and tertiary hospital
Authors: Admiraal L. A. C. , Rosman A. N. , Dolhain R. J. E. M. , West R. L. , Mulders A. G. M. G. J.
Published: March 2022

Background

Preconception care (PCC) is care prior to conception to optimize parental health, and health of the future child, through biomedical and behavioral changes. Providing PCC to all women with a wish to conceive will improve perinatal health. PCC is especially important for women with a chronic disease, such as inflammatory bowel disease (IBD) and rheumatic diseases (RD). At present PCC is not part of routine care for these women. The aim of this study is to identify facilitators and barriers on a patient and professional level regarding the provision of PCC in women with IBD and RD.

Methods

An explorative survey study among women with IBD and RD, their treating physicians and obstetric professionals was performed. Patients with a wish to conceive, pregnant women or those with a recent pregnancy (< 1 year ago) visiting the outpatient clinic of a secondary and tertiary hospital and involved physicians and obstetric professionals were eligible.

Results

A total of 71% of the IBD patients (n = 22/31) and 35% of the RD patients (n = 20/58) received a PCC consultation. PCC consultation was considered easy to enter, short in time and patients felt comfortable. Patients (71% IBD; 62% RD) preferred a personal PCC consultation with their disease specific specialist together with an obstetrician. Patients specifically wanted to receive information about the safety of medication use and disease activity following delivery. Of the included healthcare professionals 67% (n = 31) agreed PCC was applicable to their patients. Main barrier to providing PCC was lack of time and unavailability of professionals. In total 41% (n = 16) of obstetric professionals felt they had the knowledge and skills to provide PCC compared to 33% (n = 1) and 75% (n = 3) of gastroenterologists and rheumatologists, respectively.

Conclusion

Lack of awareness and urgency for the effectuation can be seen as important barriers for implementation of PCC. Due to the explorative nature generalisation of the results is not allowed. In the future, adaptation of the curricula of healthcare professionals by implementing interventions for pregnancy planning and preparation will generate awareness. Modelling of the impact of PCC might prove useful in resolving the lack of urgency for PCC realization.
Effects of adding a neurokinin-1 receptor antagonist to 5 mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis
Authors: Yamamoto Senri , Iihara Hirotoshi , Uozumi Ryuji , Kawazoe Hitoshi , Tanaka Kazuki , Fujita Yukiyoshi , Abe Masakazu , Imai Hisao , Karayama Masato , Hayasaki Yoh , Hirose Chiemi , Suda Takafumi , Nakamura Kazuto , Suzuki Akio , Ohno Yasushi , Morishige Ken-ichirou , Inui Naoki
Published: March 2022

Background

Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy.

Methods

Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching.

Results

The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0–120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine.

Conclusions

The findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based chemotherapy.
A simple CD4+ T cells to FIB-4 ratio for evaluating prognosis of BCLC-B hepatocellular carcinoma: a retrospective cohort study
Authors: Zhao Yong , Kong Ling Xiang , Feng Feng Shi , Yang Jiayin , Wei Guo
Published: March 2022

Introduction

Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + .

Methods

This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival.

Results

The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P < 0.05). Compared with that in other indices, in logistic and ANN multivariate analysis, CD4 + -to-FIB-4 ratio (CD4+/FIB-4) had the highest importance with 0.716 C-statistic and 145.93 cut-off value. In terms of overall survival rate, HIV infection was not a risk factor (P = 0.589); however, CD4+/FIB-4 ≤ 145.93 significantly affected patient prognosis (P = 0.002).

Conclusion

HIV infection does not affect the prognosis of BCLC-B HCC, but CD4+ have a significant predictive value. CD4+ played a vital role in HCC and this deserves the attention from physicians. Further, the CD4+/FIB-4 is a clinically valuable effective prognostic indicator for these patients.
Survival status and predictors of mortality among preterm neonates admitted to neonatal intensive care unit of Addis Ababa public hospitals, Ethiopia, 2021. A prospective cohort study
Authors: Birhanu Dires , Gebremichael Bereket , Tesfaye Tewodros , Tadesse Misrak , Belege Fekadeselassie , Godie Yohannes , Wodaje Markos , Tamiru Eyerusalem
Published: March 2022

Background

Preterm related complications are the single largest direct cause of neonatal deaths throughout the world, responsible for 35% of the world’s neonatal death (1.1 million deaths/year). In Ethiopia preterm related complications are still the leading cause of neonatal mortality. Identifying the hazard time to death and predictors of mortality play an important role to decrease preterm mortality. Therefore, this study aimed to determine the survival and predictors of mortality among preterm neonates admitted to neonatal intensive care unit of Addis Ababa public hospitals, Ethiopia, 2021.

Method

An institutional based prospective follow up study was conducted among 358 preterm neonates admitted to selected public hospitals of Addis Ababa, Ethiopia from February 12 to May 12, 2021. Systematic random sampling was used to recruit each sample and data was collected prospectively using structured questioner. Epi-data version 4.6 and STATA version 16 was used to data entry and analysis respectively. Kaplan Meier failure curve, Log rank tests were computed. Schoenfeld residual test was used to check overall model fitness. Cox proportional hazards models were fitted to identify independent predictors of preterm mortality.

Result

At the end of this cohort, 125(34.9%) of the neonates died, with incidence rate of 36.4/1000 (CI: 0.031–0.044) person-day with the median time to death of 6 days. Born from antepartum hemorrhage mother (AHR: 3.1, CI; 1.4–6.6), lack of Kangaroo mother care (AHR: 5.8, CI; 2.37–14.33), unable to start feeding with in 24 h of admission (AHR: 6.4, CI: 3.33–12.28), apnea (AHR: 2.4, CI: 1.3–4.7) and dehydration (AHR: 2.33, CI: 1.3–4.3) were the identified predictors of time to death.

Conclusion and recommendation

The first 7 days of admission was the hazard time to death with median time of 6 days. Being born to antepartum hemorrhage mother, lack of Kangaroo mother care, unable to start feeding with 24-h, Apnea and dehydration were the predictors of time to death. Therefore, intervention that focuses on the identified predictors could have a paramount effect to prolong time to death and reduce preterm mortality.
Patients with isolated posterior cruciate ligament rupture had a higher posterior intercondylar eminence
Authors: Weili Shi , Qingyang Meng , Nayun Chen , Yong Ma , Yuping Yang , Ping Liu , Yingfang Ao , Xi Gong
Published: March 2022

Background

To evaluate the anatomic geometry of the posterior intercondylar eminence and its association with PCL injury risk.

Methods

Patients who underwent primary PCL reconstruction from 2015 to 2018 were retrospectively analyzed. The control group included inpatients diagnosed with ACL rupture because of a sports-related accident during the same period, matched by age, gender, height, weight, and side of injury. Measurements of the height of the apex of the posterior intercondylar eminence (HPIE), the slope length (SLPIE) and the slope angle (SAPIE) of the posterior intercondylar eminence were performed using conventional MRI scans assessed by 2 blinded, independent raters. Intraclass correlation coefficients (ICCs) was used to evaluate the consistency of measurement results. Independent sample t tests, Chi-square tests, and logistic analyses were used to compare the two group, with P < 0.05 considered statistically significant.

Results

Fifty-five patients with PCL rupture met the inclusion criteria and 55 PCL-intact matched controls were included. There were no significant differences between the groups in gender (P = 1.000), limb side (P = 0.848), age (P = 0.291), BMI (P = 0.444) or height (P = 0.290). Inter-observer reproducibility was excellent agreement in HPIE, SLPIE and SAPIE of case and control groups (ICC: HPIE = 0.81, SLPIE = 0.77, SAPIE = 0.85). Patients with PCL rupture had significantly greater HPIE, SAPIE (both P < 0.001), and SLPIE (P < 0.05) than PCL-intact patients. The multivariable analysis showed that HPIE (OR, 1.62 [95% CI, 1.24–2.11], P < 0.001) and SAPIE (OR, 1.17 [95% CI, 1.05–1.31], P < 0.001) were independent factors associated with PCL rupture.

Conclusion

Through this retrospective observational study, we found that patients with PCL rupture may have a higher posterior intercondylar eminence compared to PCL-intact patients.

Level of evidence

III.
Unicentric castleman disease located in the left popliteal fossa: a case report
Authors: Lv Haijuan , Zhao Hongwei
Published: March 2022

Background

Castleman disease (CD) is a lymphoproliferative disease of unknown etiology, it can affect any lymph nodes of the body but rarely affects the popliteal fossa.

Case presentation

We present a 67-year-old woman with touching solitary painless mass in the left popliteal fossa for one week. Imaging showed multiple soft-tissue masses of different sizes in the left popliteal muscle space, the T1 weighted image showed hypointense to isointense, the fat-suppressed T2 weighted images showed subtle hypersignal intermingled with linear of hypointense,and displayed homogeneous contrast enhancement after administration of gadolinium. Complete surgical resection was performed. Pathologically demonstrated plasma cell type CD.

Conclusion

We described a rare case plasma cell type of UCD located in the popliteal fossa which might help to enrich the clinical spectrum of this rare site and unique subtype of UCD. This case illustrates that CD should be considered in the differential diagnosis of every hypervascularity soft tissue tumor in any anatomic location, especially when they occur in the region of lymph node distribution.
Geographic access to federally qualified health centers before and after the affordable care act
Authors: Behr Caroline L , Hull Peter , Hsu John , Newhouse Joseph P , Fung Vicki
Published: March 2022

Background

The Affordable Care Act (ACA) increased funding for Federally Qualified Health Centers (FQHCs). We defined FQHC service areas based on patient use and examined the characteristics of areas that gained FQHC access post-ACA.

Methods

We defined FQHC service areas using total patient counts by ZIP code from the Uniform Data System (UDS) and compared this approach with existing methods. We then compared the characteristics of ZIP codes included in Medically Underserved Areas/Populations (MUA/Ps) that gained access vs. MUA/P ZIP codes that did not gain access to FQHCs between 2011–15.

Results

FQHC service areas based on UDS data vs. Primary Care Service Areas or counties included a higher percentage of each FQHC’s patients (86% vs. 49% and 71%) and ZIP codes with greater use of FQHCs among low-income residents (29% vs. 22% and 22%), on average. MUA/Ps that gained FQHC access 2011–2015 included more poor, uninsured, publicly insured, and foreign-born residents than underserved areas that did not gain access, but were less likely to be rural (p < .05).

Conclusions

Measures of actual patient use provide a promising method of assessing FQHC service areas and access. Post-ACA funding, the FQHC program expanded access into areas that were more likely to have higher rates of poverty and uninsurance, which could help address disparities in access to care. Rural areas were less likely to gain access to FQHCs, underscoring the persistent challenges of providing care in these areas.
A comparative methylome analysis reveals conservation and divergence of DNA methylation patterns and functions in vertebrates
Authors: Al Adhami Hala , Bardet Anaïs Flore , Dumas Michael , Cleroux Elouan , Guibert Sylvain , Fauque Patricia , Acloque Hervé , Weber Michael
Published: March 2022

Background

Cytosine DNA methylation is a heritable epigenetic mark present in most eukaryotic groups. While the patterns and functions of DNA methylation have been extensively studied in mouse and human, their conservation in other vertebrates remains poorly explored. In this study, we interrogated the distribution and function of DNA methylation in primary fibroblasts of seven vertebrate species including bio-medical models and livestock species (human, mouse, rabbit, dog, cow, pig, and chicken).

Results

Our data highlight both divergence and conservation of DNA methylation patterns and functions. We show that the chicken genome is hypomethylated compared to other vertebrates. Furthermore, compared to mouse, other species show a higher frequency of methylation of CpG-rich DNA. We reveal the conservation of large unmethylated valleys and patterns of DNA methylation associated with X-chromosome inactivation through vertebrate evolution and make predictions of conserved sets of imprinted genes across mammals. Finally, using chemical inhibition of DNA methylation, we show that the silencing of germline genes and endogenous retroviruses (ERVs) are conserved functions of DNA methylation in vertebrates.

Conclusions

Our data highlight conserved properties of DNA methylation in vertebrate genomes but at the same time point to differences between mouse and other vertebrate species.
An international consensus on the essential and desirable criteria for an ‘organized’ cancer screening programme
Authors: Zhang Li , Carvalho André L. , Mosquera Isabel , Wen Tianmeng , Lucas Eric , Sauvaget Catherine , Muwonge Richard , Arbyn Marc , Weiderpass Elisabete , Basu Partha
Published: March 2022

Background

High variability in the definition and interpretation of organized cancer screening needs to be addressed systematically. Moreover, the relevance of the current practice of categorizing screening programmes dichotomously into organized or non-organized needs to be revisited in the context of considerable heterogeneity that exists in the delivery of cancer screening in the real world. We aimed to identify the essential and desirable criteria for organized cancer screening that serve as a charter of best practices in cancer screening.

Methods

We first did a systematic review of literature to arrive at an exhaustive list of criteria used by various publications to describe or define organized cancer screening, based on which, a consolidated list of criteria was generated. Next, we used a Delphi process comprising of two rounds of online surveys to seek agreement of experts to categorize each criterion into essential, desirable, or neither. Consensus was considered to have been achieved based on a predetermined criterion of agreement from at least 80% of the experts. The outcomes were presented before the experts in a virtual meeting for feedbacks and clarifications.

Results

A total of 32 consolidated criteria for an organized screening programme were identified and presented to 24 experts from 20 countries to select the essential criteria in the Delphi first round. Total 16 criteria were selected as essential with the topmost criteria (based on the agreement of 96% of experts) being the availability of a protocol/guideline describing at least the target population, screening intervals, screening tests, referral pathway, management of positive cases and a system being in place to identify the eligible populations. In the second round of Delphi, the experts selected eight desirable criteria out of the rest 16. The most agreed upon desirable criterion was existence of a specified organization or a team responsible for programme implementation and/or coordination.

Conclusions

We established an international consensus on essential and desirable criteria, which screening programmes would aspire to fulfil to be better-organized. The harmonized criteria are a ready-to-use guide for programme managers and policymakers to prioritize interventions and resources rather than supporting the dichotomous and simplistic approach of categorizing programmes as organized or non-organized.
Telomerase deficiency reflects age-associated changes in CD4+ T cells
Authors: Matthe Diana M. , Thoma Oana-Maria , Sperka Tobias , Neurath Markus F. , Waldner Maximilian J.
Published: March 2022

Background

Amongst other systemic changes, aging leads to an immune dysfunction. On the molecular level, a hallmark of aging is telomere shortening. The functional relevance of telomerase, an enzyme capable of elongating telomeres in T cells upon antigen stimulation, is not fully understood. Studying the impact of telomere shortening on CD4+ T cells and especially Th1 effector function can provide a better understanding on immune dysfunctions in elderly.

Results

We investigated T cell numbers and differentiation in telomerase-deficient (mTerc−/−) mice under steady-state conditions and the functional role of telomerase in CD4+ T cells using in vitro stimulation and Th1 polarization protocols by comparing T cells from mTerc−/− and control mice. We report reduced relative CD4+ T cell numbers in blood and secondary lymphoid organs and a relative decline in the naïve T cell population in thymus, blood and spleen of mTerc−/− mice compared to control mice. Importantly, after in vitro polarization, mTerc−/− G3 CD4+ T cells showed higher numbers of IFNγ-producing cells and reduced expression of CD28. Notably, telomerase-deficient T cells were more susceptible to inhibition of Th1 polarization by IL-6 in vitro. These results demonstrate that telomerase deficiency recapitulates several changes of CD4+ T cells seen in aged humans regarding the naïve T cell population, expression of CD28 and cytokine production.

Conclusion

Our data suggest that telomere shortening could play a key role in the aging of T cell immunity, with clinical implications for immune diseases and tumor development and that mTerc−/− mice are a suitable model to study aging-related defects of adaptive immunity.
Association of Keap1 (rs11085735) polymorphism and lncRNA MEG3 hypermethylation status with the risk of preeclampsia
Authors: Zangeneh Maryam , Heydarian Sara , Seifi Zahra , Kohsari Maryam , Rahimi Zohreh
Published: March 2022

Background

Preeclampsia (PE) is one of the complications of pregnancy. The pathogenesis of PE has not been completely understood. The aims of the present study were to investigate the role of Keap1 (rs11085735) variants and the methylation status of long non-coding RNA (lncRNA) MEG3 in the risk of PE.

Methods

In a case–control study, 150 pregnant women, including 75 PE patients and 75 healthy pregnant women recruited from Western Iran with Kurdish ethnic background, were studied for Keap1 variants using polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP). The methylation status of lncRNA MEG3 was investigated using methylation-specific PCR (MSP) among 50 preeclamptic patients and 50 controls.

Results

The frequency of Keap1 A allele was significantly lower (5.3%) in preeclamptic patients compared to controls (12.7%, p = 0.024). The frequencies of hemimethylated (UM) and full methylated (MM) lncRNA MEG3 were 94 and 6% (p = 0.04), respectively, in all patients, 86.4, and 13.6% (p = 0.04), respectively, in patients with severe preeclampsia and 98 and 0% in controls. The frequency of full methylated lncRNA MEG3 was 14.3% in early-onset preeclampsia and 2.8% in late-onset preeclampsia (p = 0.12). Patients with PE had significantly higher levels of liver biomarkers (including ALT, AST, ALP, and total bilirubin) and lower PLT counts compared to healthy pregnant women.

Conclusion

The present study suggests the presence of hypermethylation status of lncRNA MEG3 in preeclampsia that might contribute to the pathogenesis and development of preeclampsia. Also, Keap1 rs11085735 polymorphism might be involved in the risk of preeclampsia.
Combined effect of orthotic intervention and conventional exercise training on balance and gait performance in cerebral palsy: a randomized controlled trial
Authors: El-Shamy Shamekh Mohamed , El-Kafy Ehab Mohamed Abd
Published: March 2022

Background

This study aimed to examine the combined effect of orthotic intervention and conventional therapeutic exercise training on balance and gait performance in children with cerebral palsy. This study was a randomized control trial. Forty children with dyskinetic cerebral palsy of both genders with ages ranged from 12 to 16 years were included. Participants in the control and study groups received a conventional therapeutic exercise training program for two 2 h ours per session. The treatment program was conducted three sessions per week, for twelve 12 successive weeks. Children in the study group additionally wore TheraTogs orthotic undergarment with the strapping system. Pediatric Balance Scale score and postural stability indices (overall, anteroposterior , and mediolateral) evaluated by the Biodex Balance System were assessed (in both groups) at baseline and after 12 weeks of treatment. The changes of step length, gait cycle time, cadence, and velocity were also measured by an electronic walkway.

Results

Children in the study group showed significant improvements in the scores of all the measured variables post-treatment compared to the control group (P < 0.05). The P -values for overall, anteroposterior and mediolateral postural stability indices were 0.011, 0.014, and 0.021, respectively. The P -values for Pediatric Balance Scale score, step length, gait cycle time, cadence, and velocity were 0.001, 0.023, 0.041, 0.011, and 0.013 respectively.

Conclusions

Conventional therapeutic exercise training combined with orthotic intervention were more effective in improving balance and gait performance in children with dyskinetic cerebral palsy.

Trial registration

The ClinicalTrial.gov PRS (NCT04990193).

Registered 4 August 2021 - Retrospectively registered.
Effective medium theory of random regular networks
Authors: Damavandi O. K. , Manning M. L. , Schwarz J. M.
Published: March 2022

Disordered spring networks can exhibit rigidity transitions, due to either the removal of material in over-constrained networks or the application of strain in under-constrained ones. While an effective medium theory (EMT) exists for the former, there is none for the latter. We, therefore, formulate an EMT for random regular, under-constrained spring networks with purely geometrical disorder to predict their stiffness via the distribution of tensions. We find a linear dependence of stiffness on strain in the rigid phase and a nontrivial dependence on both the mean and standard deviation of the tension distribution. While EMT does not yield highly accurate predictions of shear modulus due to spatial heterogeneities, it requires only the distribution of tensions for an intact system, therefore making it an ideal starting point for experimentalists quantifying the mechanics of such networks.
Safety and Efficacy of the Off-Label Use of Pipeline Embolization Device Based on the 2018 Food and Drug Administration-Approved Indications for Intracranial Aneurysms: A Single-Center Retrospective Cohort Study
Authors: Enriquez-Marulanda Alejandro , Penumaka Anirudh , Ogilvy Christopher S. , Thomas Ajith J. , Moore Justin M.
Published: March 2022

BACKGROUND:

The pipeline embolization device (PED; ev3/Covidien) has proven safe and effective for treating selected intracranial aneurysms. This device's versatility and popularity have driven increased interest in expanding the latest 2018 Food and Drug Administration–approved indications.

OBJECTIVE:

To compare “off-label” and “on-label” PED treatment.

METHODS:

Retrospective analysis of aneurysms treated with PED at a single center from 2013 to 2019. Comparisons were made based on the 2018 Food and Drug Administration–approved indications.

RESULTS:

A total of 492 treated aneurysms were included (65.2% on-label and 34.8% off-label). Aneurysm complete and near-complete occlusion rate was nonsignificantly lower in the off-label group (80.9% vs 85.7%; P = .19). Off-label treatment had higher rate of poor functional outcomes (modified Rankin Scale [mRS] >2: 10.3% vs 3.5%; P = .002). Although pretreatment mRS was already higher in the off-label group (5.3% vs 0.3%; P < .001) and there were no differences in mRS worsening during follow-up (5.5% vs 2.9%; P = .15). We also found a trend to a higher rate of intracranial hemorrhagic complications in the off-label group (4.7% vs 1.6%; P = .05), but there were no differences in hemorrhages requiring surgical intervention (1.8% vs 1.3%; P = .65). There were no differences in retreatment, thromboembolic complications, and mortality rates.

CONCLUSION:

Off-label PED treatment may be considered for select aneurysms, which are challenging to treat with other techniques. These cases have similar complete and near-complete occlusion rates compared with on-label cases. There are, however, higher risks of poor functional outcomes despite similar rates of thromboembolic and hemorrhagic complications. This is partly explained by the significantly higher pretreatment mRS score in the off-label group.
Stereotactic Radiosurgery Compared With Active Surveillance for Asymptomatic, Parafalcine, and Parasagittal Meningiomas: A Matched Cohort Analysis From the IMPASSE Study
Authors: Pikis Stylianos , Mantziaris Georgios , Bunevicius Adomas , Islim Abdurrahman I. , Peker Selcuk , Samanci Yavuz , Nabeel Ahmed M. , Reda Wael A. , Tawadros Sameh R. , El-Shehaby Amr M. N. , Abdelkarim Khaled , Emad Reem M. , Delabar Violaine , Mathieu David , Lee Cheng-chia , Yang Huai-che , Liscak Roman , May Jaromir , Alvarez Roberto Martinez , Patel Dev N. , Kondziolka Douglas , Bernstein Kenneth , Moreno Nuria Martinez , Tripathi Manjul , Speckter Herwin , Albert Camilo , Bowden Greg N. , Benveniste Ronald J. , Lunsford L. Dade , Jenkinson Michael D. , Sheehan Jason
Published: March 2022

BACKGROUND:

The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial.

OBJECTIVE:

To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas.

METHODS:

Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts.

RESULTS:

There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P < .001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%).

CONCLUSION:

Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death.
In vitro culture of ovine embryos up to early gastrulating stages
Authors: Ramos-Ibeas Priscila , González-Brusi Leopoldo , Used María Torres , Cocero María Jesús , Marigorta Pilar , Alberio Ramiro , Bermejo-Álvarez Pablo
Published: March 2022

Developmental failures occurring shortly after blastocyst hatching from the zona pellucida constitute a major cause of pregnancy losses in both humans and farm ungulates. The developmental events occurring following hatching in ungulates include the proliferation and maturation of extra-embryonic membranes – trophoblast and hypoblast – and the formation of a flat embryonic disc, similar to that found in humans, which initiates gastrulation prior to implantation. Unfortunately, our understanding of these key processes for embryo survival is limited because current culture systems cannot sustain ungulate embryo development beyond hatching. Here, we report a culture system that recapitulates most developmental landmarks of gastrulating ovine embryos: trophoblast maturation, hypoblast migration, embryonic disc formation, disappearance of the Rauber's layer, epiblast polarization and mesoderm differentiation. Our system represents a highly valuable platform for exploring the cell differentiation, proliferation and migration processes governing gastrulation in a flat embryonic disc and for understanding pregnancy failures during the second week of gestation.

This article has an associated ‘The people behind the papers’ interview.
Naphthoquinone-induced arylation inhibits Sirtuin 7 activity
Authors: Sirri Valentina , Berthelet Jérémy , Brookes Oliver , Roussel Pascal
Published: March 2022

Natural or synthetic naphthoquinones have been identified to interfere with biological systems and, in particular, exhibit anticancer properties. As redox cyclers, they generate reactive oxygen species in cells and, as electrophiles, they react with nucleophiles, mainly thiols, and form covalent adducts. To further decipher the molecular mechanism of action of naphthoquinones in human cells, we analyzed their effects in HeLa cells. First, we demonstrated that the naphthoquinones menadione and plumbagin inhibited the nucleolar NAD+-dependent deacetylase Sirtuin 7 in vitro. As assessed by their inhibition of rDNA transcription, pre-rRNA processing and formation of etoposide-induced 53BP1 foci, menadione and plumbagin also inhibited Sirtuin 7 catalytic activity in vivo. Second, we established that when sulfhydryl arylation by menadione or plumbagin was prevented by the thiol reducing agent N-acetyl-L-cysteine, the inhibition of Sirtuin 7 catalytic activity was also blocked. Finally, we discuss how inhibition of Sirtuin 7 might be crucial in defining menadione or plumbagin as anti-tumor agents that can be used in combination with other anti-tumor strategies.
Vertical Loading Rate Is Not Associated with Running Injury, Regardless of Calculation Method
Authors: SCHMIDA ELIZABETH A. , WILLE CHRISTA M. , STIFFLER-JOACHIM MIKEL R. , KLIETHERMES STEPHANIE A. , HEIDERSCHEIT BRYAN C.
Published: March 2022

Introduction

Loading rate (LR), the slope of the vertical ground reaction force (vGRF), is commonly used to assess running-related injury risk. However, the relationship between LR and running-related injuries, including bone stress injuries (BSI), is unclear. Inconsistent findings may result from the numerous LR calculation methods that exist and their application across different running speeds.

Purpose

This study aimed to assess the influence of calculation method and running speed on LR values and to determine the association of LR during healthy running with subsequent injury.

Methods

Healthy preseason running data and subsequent injury records from Division I cross-country athletes (n = 79) over four seasons (2015–2019) at 2.68 m·s−1, preferred training pace, and 4.47 m·s−1 were collected. LR at each speed was calculated four ways: 1) maximum and 2) average slope from 20% to 80% of vGRF magnitude at impact peak (IP), 3) average slope from initial contact to IP, and 4) average slope from 3% to 12% of stance time. Linear mixed effects models and generalized estimation equations were used to assess LR associations.

Results

LR values differed depending on speed and calculation method (P value <0.001). The maximum slope from 20% to 80% of the vGRF at 4.47 m·s−1 produced the highest LR estimate and the average slope from initial contact to IP at 2.68 m·s−1 produced the lowest. Sixty-four injuries (20 BSI) were observed. No significant association was found between LR and all injuries or BSI across any calculation method (P values ≥0.13).

Conclusions

Calculation method and running speed result in significantly different LR values. Regardless of calculation method, no association between LR and subsequent injury was identified. Thus, healthy baseline LR may not be useful to prospectively assess running-related injury risk.