bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of HPV11 E7 in modulating STING-dependent interferon β response in recurrent respiratory papillomatosis
Authors: Chen Lijuan , Hu Huiying , Pan Yufei , Lu Yuanyuan , Zhao Mengyuan , Zhao Yun , Wang Lixin , Liu Kai , Yu Zhenkun
Published: April 2024

Recurrent respiratory papillomatosis (RRP) is a rare benign tumor caused mainly by the infection of the respiratory tract epithelial cells by the human papillomavirus (HPV) type 6/11. However, the specific mechanisms underlying the inhibition of the host’s innate immune response by HPV remain unclear. For this purpose, we employed single-cell RNA sequencing to analyze the states of various immune cells in RRP samples post-HPV infection and utilized a cellular model of HPV infection to elucidate the mechanisms by which HPV evades the innate immune system in RRP. The results revealed distinct immune cell heterogeneity in RRP and demonstrated that HPV11 E7 can inhibit the phosphorylation of the stimulator of interferon genes protein, thereby circumventing the body’s antiviral response.
In vitro
co-culture experiments demonstrated that stimulation of macrophages to produce interferon-beta induced the death of HPV-infected epithelial cells, also reducing HPV viral levels. In summary, our study preliminarily identifies the potential mechanisms by which HPV evades the host’s antiviral immune response, as well as the latent antiviral functions exhibited by activated macrophages. This research serves as an initial exploration of antiviral immune evasion in RRP, laying a solid foundation for investigating immunotherapeutic approaches for the disease.

IMPORTANCE

Surgical tumor reduction is the most common treatment for recurrent respiratory papillomatosis (RRP). One of the characteristics of RRP is its persistent recurrence, and multiple surgeries are usually required to control the symptoms. Recently, some adjuvant therapies have shown effectiveness, but none of them can completely clear human papillomavirus (HPV) infection, and thus, a localized antiviral immune response is significant for disease control; after all, HPV infection is limited to the epithelium. Inhibition of interferon-beta (IFN-β) secretion by HPV11 E7 viral proteins in epithelial cells by affecting stimulator of interferon genes phosphorylation may account for the persistence of low-risk HPV replication in the RRP. Moreover, suppression of the IFN-I pathway in RRP cell types might provide clues regarding the hyporeactive function of local immune cells. However, activation of macrophage groups to produce IFN-β can still destroy HPV-infected cells.
Complete genome sequence of
Microbacterium paraoxydans
phage Damascus
Authors: Bearhart Julisa M. , Bethke Jenna L. , Christian Cassie S. , Cour Faith N. , Creasey Karleigh R. , Crowe Emily J. , Dahl Julia G. , Hanson Lindsey A. , Jaecks Abby L. , Lamantia Vincent A. , Madison Mercedes , Roskowiak Autumn L. , Scheberl Justin D. , VanEperen Bekkah M. , Wurst Morgan E. , Klyczek Karen K.
Published: April 2024

Phage Damascus was isolated from soil in northwestern Wisconsin using
Microbacterium paraoxydans
as the host. The Damascus genome is 56,477 bp with 3′ single-stranded overhangs and 56.5% G+C content. Damascus was assigned to cluster EL and shares 42.6%–91.7% gene content with the three other phages in this cluster.
Sputtering Yields of Beryllium and Tungsten by Various Atoms from Hydrogen to Tungsten
Authors: Mikhailov V. S. , Babenko P. Yu. , Shergin A. P. , Zinoviev A. N.
Published: April 2024

Sputtering yields of targets made of Be and W, promising materials for the first wall and the divertor of the ITER tokamak, are calculated in a wide range of projectile energies from 10 to 100 000 eV by computer simulation. The following atoms were chosen as bombarding particles: H, D, T, He, Be, C, N, O, Ne, Ar, and W. It is demonstrated that the shape of the surface strongly impacts the obtained results. The limiting cases of a planar potential barrier (a smooth surface) and a spherical potential barrier (a rough surface) are analyzed. The data on the average energy and angular distribution of sputtered atoms needed for calculation of the impurity influx into tokamak plasma are obtained. The influx of atoms of the wall material into the ITER tokamak plasma upon wall sputtering by fluxes of fast deuterium and tritium atoms leaving plasma is estimated.
Pleisiomonas shigelloidesbacteremia after catfish injury
Authors: Glatz Catherine , Arastu Asad , Train Meghan K
Published: April 2024

This case ofPleisimonas shigelloidesbacteremia resulting after a catfish barb injury highlights an unusual presentation of a common condition that requires alternative therapy for successful treatment. An otherwise healthy male in his early 40s presented to the emergency department with sepsis and rapidly spreading cellulitis shortly after a catfish injury at a freshwater lake. His broad-spectrum antibiotics were narrowed to ciprofloxacin whenP. shigelloidesgrew from his blood culture. The case presents a unique mode of bacteremia, as usuallyP. shigelloidesbacteremia develops in immunocompromised hosts after bowel wall translocation. The venomous nature of catfish barbs also contributed to the severity and rapidity of his presentation secondary to the local tissue effects of envenomation. With proper antibiotics and supportive care, he made a full recovery.
Chronic disease prevention and screening outcomes for patients with and without financial difficulty: a secondary analysis of the BETTER WISE cluster randomised controlled trial
Authors: Aubrey-Bassler Kris , Patel Dhruvesh , Fernandes Carolina , Lofters Aisha K , Campbell-Scherer Denise , Meaney Christopher , Moineddin Rahim , Wong Tracy , Pinto Andrew David , Shea-Budgell Melissa , McBrien Kerry , Grunfeld Eva , Manca Donna P
Published: April 2024

Objective

Building on Existing Tools To improvE chronic disease pRevention and screening in primary care Wellness of cancer survIvorS and patiEnts (BETTER WISE) was designed to assess the effectiveness of a cancer and chronic disease prevention and screening (CCDPS) programme. Here, we compare outcomes in participants living with and without financial difficulty.

Design

Secondary analysis of a cluster-randomised controlled trial.

Setting

Patients of 59 physicians from 13 clinics enrolled between September 2018 and August 2019.

Participants

596 of 1005 trial participants who responded to a financial difficulty screening question at enrolment.

Intervention

1-hour CCDPS visit versus usual care.

Outcome measures

Eligibility for a possible 24 CCDPS actions was assessed at baseline and the primary outcome was the percentage of eligible items that were completed at 12-month follow-up. We also compared the change in response to the financial difficulty screening question between baseline and follow-up.

Results

55 of 265 participants (20.7%) in the control group and 69 of 331 participants (20.8%) in the intervention group reported living with financial difficulty. The primary outcome was 29% (95% CI 26% to 33%) for intervention and 23% (95% CI 21% to 26%) for control participants without financial difficulty (p=0.01). Intervention and control participants with financial difficulty scored 28% (95% CI 24% to 32%) and 32% (95% CI 27% to 38%), respectively (p=0.14). In participants who responded to the financial difficulty question at both time points (n=302), there was a net decrease in the percentage of participants who reported financial difficulty between baseline (21%) and follow-up (12%, p<0.001) which was similar in the control and intervention groups. The response rate to this question was only 51% at follow-up.

Conclusion

The BETTER intervention improved uptake of CCDPS manoeuvres in participants without financial difficulty, but not in those living with financial difficulty. Improving CCDPS for people living with financial difficulty may require a different clinical approach or that social determinants be addressed concurrently with clinical and lifestyle needs or both.

Trial registration number

ISRCTN21333761.
Impact of supplementation with iron–folic acid (IFA) and vitamin D3compared with IFA alone on haemoglobin levels in elderly people with mild-to-moderate anaemia: protocol for the double-blind, randomised, placebo-controlled Iron and vitamin D trial in Elderly Anemia (IDEA)
Authors: Ahamed Farhad , Jaiswal Abhishek , Sahoo Sibasish , Ghosh Tandra , Kaur Amandeep , Rehman Tanveer , Goswami Kalyan
Published: April 2024

Introduction

Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron–folic acid (IFA) with vitamin D3on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels.

Methods and analysis

This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3levels will be randomised into the intervention (IFA and vitamin D3supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks.

Ethics and dissemination

Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities.

Trial registration number

CTRI/2022/05/042775.

Protocol version

Version 1.0.
Missed nursing care and its associated factors in public hospitals of Bahir Dar City, Northwest Ethiopia: a cross-sectional study
Authors: Abere Yirgalem , Biresaw Henok , Misganaw Mekides , Netsere Biniyam , Adal Ousman
Published: April 2024

Objectives

The aim of this study was to investigate the prevalence of missed nursing care and its associated factors among public hospitals in Bahir Dar City, Northwest Ethiopia.

Design

An institution-based cross-sectional study was conducted among 369 randomly selected nurses.

Setting

The study was conducted in primary and secondary-level public hospitals in Bahir Dar City.

Participants

Nurses who had worked in hospitals in Bahir Dar City were included.

Intervention

No intervention was needed in this study.

Primary and secondary outcome measures

A binary logistic regression model was used for statistical analysis. Statistical significance of the association between outcome variables and independent variables was declared at a p value of <0.05 with a 95% CI.

Results

The prevalence of missed nursing care in this study was 46.3% (95% CI: 41.7% to 50.9%). The activities most frequently missed were physical examination (56.4%), patient discharge planning and teaching (50.9%), providing emotional support to the patient and family (50.8%), monitoring input and output (50.2%), assisting with patient ambulation (48.5%) and documentation (48%). Factors associated with missed nursing care include: male professionals (adjusted OR (AOR): 2.9, 95% CI: 1.8 to 4.8), those who had not received on-the-job training (AOR: 2.2, 95% CI: 1.4 to 3.6), those who worked full 24-hour shifts (AOR: 3.7, 95% CI: 2.0 to 6.5), those who were dissatisfied with the level of teamwork (AOR: 4.6, 95% CI: 2.8 to 7.6) and those who had an intention to leave the nursing profession (AOR: 1.8, 95% CI: 1.1 to 2.9). These factors were statistically associated with missed nursing care.

Conclusion

A significant proportion of nurses missed essential nursing care activities. Efforts should be made to enhance training, improve teamwork among nurses, provide stability and adjust work shifts to mitigate this issue.
Skin closUre in carPal tunnEl Release (SUPER): protocol for a blinded randomised controlled trial comparing absorbable and non-absorbable sutures in carpal tunnel release
Authors: Savolainen Aukusti , Nietosvaara Yrjänä , Sirola Joonas , Hytönen Mikael , Reito Aleksi , Heikkinen Noora , Räisänen Mikko Petteri
Published: April 2024

Introduction

Carpal tunnel syndrome is a common disorder affecting a substantial portion of the general population. Surgical intervention is often deemed necessary, with the median nerve release being one of the most frequent operations. Optimising all the aspects of this procedure can enhance patient satisfaction with the treatment.

Methods and analysis

We aim to determine the differences in the aesthetic outcome of the scar as well as the pain experienced during the healing process between the use of absorbable and non-absorbable sutures. The primary outcome measure will be the patients’ subjective satisfaction with the aesthetic appearance of the scar 1 year after the operation. Secondary outcomes will include a similar evaluation of the aesthetics performed by a blinded outcome assessor, as well as pain experienced by the patients during the 2 weeks postoperatively. The severity and improvement of the patients’ symptoms will also be measured by a Finnish version of the Boston Carpal Tunnel Questionnaire. Costs will be evaluated for both groups. Safety of the wound closure will be followed and reported.

Ethics and dissemination

This protocol was approved by the Research Ethics Committee of the Northern Savo Hospital District (2319/2021). The trial will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The results will be disseminated through publication in peer-reviewed journals.

Trial registration number

NCT05503719.
The role of extracorporeal life support and timing of repair in infants with congenital diaphragmatic hernia
Authors: Gehle Daniel B , Meyer Logan C , Jancelewicz Tim
Published: April 2024

Extracorporeal life support (ECLS) serves as a rescue therapy for patients with congenital diaphragmatic hernia (CDH) and severe cardiopulmonary failure, and only half of these patients survive to discharge. This costly intervention has a significant complication risk and is reserved for patients with the most severe disease physiology refractory to maximal cardiopulmonary support. Some contraindications to ECLS do exist such as coagulopathy, lethal chromosomal or congenital anomaly, very preterm birth, or very low birth weight, but many of these limits are being evaluated through further research. Consensus guidelines from the past decade vary in recommendations for ECLS use in patients with CDH but this therapy appears to have a survival benefit in the most severe subset of patients. Improved outcomes have been observed for patients treated at high-volume centers. This review details the evolving literature surrounding management paradigms for timing of CDH repair for patients receiving preoperative ECLS. Most recent data support early repair following cannulation to avoid non-repair which is uniformly fatal in this population. Longer ECLS runs are associated with decreased survival, and patient physiology should guide ECLS weaning and eventual decannulation rather than limiting patients to arbitrary run lengths. Standardization of care across centers is a major focus to limit unnecessary costs and improve short-term and long-term outcomes for these complex patients.
Computational simulation of impact perforation of polymeric-foam core sandwiched composites with different skin–face configurations
Authors: Elnasri Ibrahim , Almagableh Ahmed , Gherissi Abderraouf
Published: April 2024

The normal and oblique impact perforation responses of composite sandwich panels based on a Rohacell polymeric-foam core are numerically investigated at high impact energies (>60 J). A cylindrical form factor with a diameter of 140 mm and a thickness of 15 mm is selected for the sandwich specimens. Four different stacking sequences of 1 mm carbon/epoxy face sheets are considered (i.e., quasi-isotropic, cross-ply, angle-ply, and unidirectional stacking). A computational model was constructed using LS-DYNA finite element software and an inverse perforation testing scheme adapted with a split Hopkinson bar and confirmed by comparing these results with those obtained using the free shooting projectile-target testing schemes published in the literature. The effects of impact energy, failure modes, impact angles, and damage key parameters are analyzed. The results reveal the contact force versus displacement curves are highly influenced by the impact energy increases. The stacking sequence of the face sheets does not influence the energy absorption capacity. However, the maximum absorbed energy increases with an increasing impact angle up to 20°. Using Hopkinson bars in conjunction with the virtual inverse perforation testing approach is effective for examining the response of sandwich composites at high impact energies.
Thermal performance appraisal of hybrid and nanofluid flow between a cone and a disk with variable thermal conductivity, viscous dissipation, and Joule heating
Authors: Li Shuguang , Gul Hina , Ramzan Muhammad , Kadry Seifedine , Saleel C. Ahamed
Published: April 2024

In many engineering systems, hybrid and nanofluids are influenced by their respective thermophysical characteristics. Lately, several models have been envisaged to foresee the hybrid and nanofluid attributes. The properties of hybrid nanofluids (HNFs) as potential heat transfer fluids are controlled by numerous aspects such as solid part size, volume fraction, and temperature. Considering the interesting facts of the hybrid and nanofluid flows, we in this exploration examined the thermal performance comparison of both types of fluid flows. The nanofluid and HNF are composed of molybdenum disulfide (MoS[Formula: see text]/kerosene oil and silicon dioxide–molybdenum disulfide (SiO2–MoS[Formula: see text]/kerosene oil, respectively. The flows are taken in a canonical gap between the cone and the disk. Both the cone and the disk may be rotating or stationary. The novelty of the computational model is enhanced by discussing the effects of viscous dissipation, Joule heating, and the variable thermal conductivity with convective condition. The Tawari and Das model is designed to analyze the heat transfer performance of the assumed fluid flows. The assumed fluid model is transmuted into the set of differential equations that are dealt numerically with the bvp4c MATLAB approach. The results are displayed in tables and graphical forms. For elevating estimations of the Eckert number, the heat transmission rate is found to be more significant in the disk than cone. It is also learned that hybrid nanoliquid heat transfer performance outperforms nanoliquid. The fluid velocity increases by raising the nanoparticle volume fraction [Formula: see text], and is decreasing for a higher magnetic field parameter. With the elevating estimates of thermal conductivity, it is shown that the cone transmits heat more quickly whereas the disc transmits heat more slowly. The thermal conductivity parameter increases the probability of collision of the liquid particles, that ultimately upsurges fluid heat transmission rate.
Online English Resource Integration Algorithm based on high-dimensional Mixed Attribute Data Mining
Authors: Zhou Zhiyu
Published: April 2024

To improve the scalability of resources and ensure the effective sharing and utilization of online English resources, an online English resource integration algorithm based on high-dimensional mixed-attribute data mining is proposed. First, an integration structure based on high-dimensional mixed-attribute data mining is constructed. According to this structure, the characteristics of online English resources are extracted, and historical data mining is carried out in combination with the spatial distribution characteristics of resources. In this way, the spatial mapping function of features is established, and the optimal clustering center is designed according to the clustering and fusion structure of online English resources. At this node, the clustering and fusion of online English resources are carried out. According to the fusion results, the distribution structure model of online English resources is constructed, and the optimization research of the integration algorithm of online English resources is carried out. The experimental results show that the integration optimization efficiency of the proposed algorithm is 89%, and the packet loss rate is 0.19%. It has good integration performance, and can realize the integration of multi-channel and various forms of online English resources.
Assessing the benefits of an online prematriculation anatomy workshop on knowledge acquisition and anatomy competency in a Doctor of Physical Therapy program
Authors: Bains Mona , Kaliski Debora Z.
Published: April 2024

This paper presents the findings of a retrospective study examining the effectiveness of an online prematriculation anatomy workshop on knowledge acquisition and first-semester anatomy competency following the success of a previously offered peer-led onsite workshop. To our knowledge, this is the first report of an online prematriculation program that successfully introduces graduate-level learning expectations and access to anatomical resources leading to improved anatomy competency in an allied health professional program.
A New Phase for WNK Kinase Signaling Complexes as Biomolecular Condensates
Authors: Boyd-Shiwarski Cary R. , Shiwarski Daniel J. , Subramanya Arohan R.
Published: April 2024

The purpose of this review is to highlight transformative advances that have been made in the field of biomolecular condensates, with special emphasis on condensate material properties, physiology, and kinases, using the With-No-Lysine (WNK) kinases as a prototypical example. To convey how WNK kinases illustrate important concepts for biomolecular condensates, we start with a brief history, focus on defining features of biomolecular condensates, and delve into some examples of how condensates are implicated in cellular physiology (and pathophysiology). We then highlight how WNK kinases, through the action of “WNK droplets” that ubiquitously regulate intracellular volume and kidney-specific “WNK bodies” that are implicated in distal tubule salt reabsorption and potassium homeostasis, exemplify many of the defining features of condensates. Finally, this review addresses the controversies within this emerging field and questions to address.
The Contribution of Using Cooperative Learning Methods on Students’ Achievement and Retention in Secondary Schools during Chemistry Lesson
Authors: Simesso Melkamu Duguma , Gutu Tariku Sime , Tarekegn Wudu Melese
Published: April 2024

This investigation was made necessary as a result of the inconsistently poor achievement that secondary school students have repeatedly achieved on chemistry exams in Nekemte Administration Town throughout the years. These poor results can be credited with the reality that the majority of secondary school teachers use ineffective teaching strategies that do not encourage students’ active learning through involvement. Therefore, this investigation examined the contribution of cooperative learning on high school students’ chemistry achievement and retention. Quasi-experimental research with a pretest–posttest nonequivalent control group design was adopted. One hundred twenty-eight students were involved, drawn from two intact classes in two different schools. A reliability value of 0.89 for the chemistry achievement test was employed. The findings of this investigation demonstrated a significant difference between students instructed through cooperative learning and students instructed using lecture-based teaching in terms of their chemistry achievement and retention (t (126) = 5.544, p<0.001) and (t (126) = 4.167, p<0.001), respectively. Pretest, posttest, and retention test results of the treatment group showed a significant difference that favors the posttest (r = 0.91, p<0.001) and retention test (r = 0.81, p<0.001). Gender differences did not exist in chemistry achievement (t (62) = −1.243, p<0.001) and retention (t (62) = −1.036, p<0.001).
Table S5 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

Genomic coordinates of super enhancer regions, relative to DOCRs identified in control and MG132 treated cells, relating to Figure 5.
Table S4 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

List of genomic coordinates of nongenic TSS (uTSS) and nearby gene expression, relating to Figure 3.
Table S3 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

List of genomic coordinates of bidirectional and PROMPT TSS gene pairs and corresponding gene expression changes, relating to Figure 3.
Table S2 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

List of genomic coordinates of open (OCR) and differential open chromatin regions (DOCR) in cells treated with MG132, relating to Figure 1.
Figure S2 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

Shows effects of proteasome inhibition on different transcription initiation patterns.
Figure S1 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

Shows detailed analysis of changes in DNA accessibility in cells treated with MG132.
FIGURE 3 from Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer
Authors: Kinyamu H. Karimi , Bennett Brian D. , Ward James M. , Archer Trevor K.
Published: April 2024

Proteasome inhibition exhibits specific effects on divergent transcription. A, Heat maps showing differential signal for start RNA, DNA accessibility (ATAC), RNAPII (Ser5P), and active histone marks (K27ac, K122ac, K4me1, K4me3) at genic TSSs with divergent transcription that overlap GAIN DOCRs. B, Heat maps as in A, overlap LOST DOCRs. Signal spans ±500 bases from the TSSs and is ranked by distance between sense and antisense TSS pairs, where TSSs at the top have the shortest distance between pairs. TSSs are split by category into Promoter Upstream Transcripts (PROMPT) and Bidirectional (head-to-head) TSS pairs. N is the number of TSS pairs in each category. C, Scatter plot showing gene expression changes of bidirectional (head-to-head) TSS pairs. TSS pairs are colored by gene class, where each TSS in the pair is either protein coding (PC) or non-coding (NC). D, Violin plot showing gene expression changes of genic TSSs associated with promoter upstream transcript (PROMPT) category. Significantly different genes (FDR ≤ 0.05, log2FC±1) are colored red (upregulated) and blue (downregulated). Gold labeled are non-coding genes. E, Heat maps showing differential signal of features in A at non-genic TSSs that overlap GAIN DOCRs. F, Heat maps showing differential signal of features in A at non-genic TSSs that overlap LOST DOCRs. TSSs are split by genomic category into gene body and intergenic. G, Violin plot showing gene expression changes of genes closest to non-genic TSSs, which are split by genomic category into gene body and intergenic. N is the number of TSS pairs in each category.
Implications of Switching from Conventional to Electronic Cigarettes on Quality of Life and Smoking Behaviour: Results from the EQualLife Trial
Authors: Rabenstein Andrea , Czermak Lilian , Fischer Elke , Kahnert Kathrin , Pogarell Oliver , Jörres Rudolf A. , Nowak Dennis , Rüther Tobias
Published: April 2024

Introduction: Electronic cigarettes and “vaping” have become popular since their appearance in Europe and the USA in approximately 2006. They are often perceived as having fewer health risks than conventional cigarettes, which makes them of interest as a support tool in smoking cessation. However, its efficacy regarding cessation or reduction of smoking under real-life conditions remains controversial. Our objective was to clarify this question in an observational study of smoking habits after initiating vaping without targeted intervention, as compared to a validated cessation programme. Methods: From October 2015 to April 2018, 80 subjects (60 in the e-cigarette group and 20 in the supervised smoking cessation group) were included in two trial visits, one at the start of the trial and the second after 3 months, plus 4 questionnaire surveys: at the start of the trial and after a 1, 2, and 3 month period. The questionnaire included a nicotine use inventory, a modified Fagerström test for nicotine dependence, and the WHO-QOL-BREF survey. Results: E-cigarettes were effective, leading to a significant (p < 0.03) reduction (p < 0.03) in tobacco consumption and nicotine dependence, with an abstinence rate of 43% after 3 months. Compared to participants in the smoking cessation programme, their use was not associated with an improvement in quality of life during the quitting attempt, and there were no significant differences in clinical symptoms between groups. The reduction in nicotine dependence was more pronounced (p < 0.012) for the smoking cessation programme, with higher abstinence rates (p = 0.011 after 12 weeks) and lower (p < 0.003) remaining tobacco consumption compared to electronic cigarettes. Discussion/Conclusions: The use of electronic cigarettes reduced nicotine dependence and tobacco consumption, but a supervised smoking cessation programme was superior in terms of achieved cessation in both regards. Electronic cigarettes did not improve the quality of life. Since e-cigarettes could be associated with long-term health risks, their usefulness in smoking cessation remains questionable, and a professionally guided and validated smoking cessation programme still appears to be superior and preferable, in terms of achieved cessation. Although this trial is limited regarding the number of participants and follow-up time, it highlights the need for additional, large clinical trials evaluating the efficacy of e-cigarettes for smoking cessation in comparison to a professionally guided smoking cessation programme.
Predicting the Speed of Response to Omalizumab in Chronic Spontaneous Urticaria
Authors: Keskinkaya Zeynep , Kaya Özge , Işık Mermutlu Selda , Öğretmen Zerrin
Published: April 2024

Introduction: Two distinct chronic spontaneous urticaria (CSU) endotypes, IgE-mediated autoallergic and IgG-mediated autoimmune, were defined based on the response patterns to omalizumab. However, the coexistence of IgE and IgG autoantibodies in a subset of patients might complicate the prediction of the treatment outcomes. This study aimed to evaluate the effectiveness and safety of omalizumab in CSU patients, focusing on the factors predicting the response patterns. Methods: This was a retrospective cross-sectional single-center study investigating CSU patients treated with omalizumab for at least 6 months between September 2015 and February 2023. Patients were evaluated regarding demographics, clinical findings, baseline laboratory parameters, treatment outcomes, and side effects. Early and late responders were defined depending on the time for response, within or after 3 months, respectively. Results: Among 82 patients, 75 (91.5%) responded to omalizumab during the first 6 months, classified as early (n = 51) and late responders (n = 24). The IgG anti-thyroid peroxidase (anti-TPO)/total IgE ratio was an independent predictor for determining the speed of response (p < 0.05). Of 29 patients who discontinued omalizumab, 19 (65.5%) experienced relapse with a good response to retreatment (n = 18/19, 94.7%). Early responders relapsed more frequently than late responders (77.3% vs. 28.6%) (p < 0.05). Only mild side effects were observed in a minority of patients (n = 8/82, 9.8%). Conclusion: Omalizumab is an effective and safe treatment in CSU. The IgG anti-TPO/total IgE ratio seems a valuable tool to predict the early and late responders, the former having a higher possibility of relapse upon drug withdrawal.
Alcohol Use and Mental Health: How Genetic Information Can Help Unravel Their Relationship
Authors: Visontay Rachel , van de Weijer Margot P. , Treur Jorien L.
Published: April 2024

Background: Traditional epidemiological evidence suggests various associations exist between alcohol and mental/cognitive health outcomes. However, whether these reflect causal relationships remains unclear. Mendelian randomization (MR) – a kind of instrumental variable analysis using genetic variants to proxy for an exposure of interest – has the potential to improve causal inference from observational data. Summary: In the first part of this review, the challenges of causal inference in the field are discussed, and a theoretical and practical introduction to the technique of MR is given. Next, we report on literature searches performed to update a previous systematic review of MR studies evaluating alcohol-mental health relationships. Twelve relevant studies were identified and considered in the context of the 22 studies included in the previous review. While the reviewed MR literature suggests possible causal relationships/a lack thereof, for the most part, the nature of causal relationships between alcohol and mental health remains unclear. Key Messages: MR is beginning to yield valuable insights into the causal effects of (problematic) alcohol consumption on mental and cognitive health outcomes. Future studies must be mindful of the technique’s underlying assumptions and should allow for potential nonlinearity in relationships. Triangulating across sensitivity methods within MR studies, as well as between MR studies and other methods for enhanced causal inference, will be crucial.
Footwear and Falls in Long-Term Residential Aged Care Facilities: An Analysis of Video Capture Data
Authors: Menz Hylton B. , Bergin Shan M. , McClelland Jodie A. , Munteanu Shannon E.
Published: April 2024

Introduction: Several footwear characteristics have been shown to affect balance and gait patterns and may therefore influence the risk of falling in older adults. However, attributing a link between footwear and falls is inherently difficult as it often relies on self-report which may be inaccurate. Methods: Archival video recordings of falls that occurred in two long-term residential aged care facilities were initially screened to determine whether the footwear worn at the time (barefoot, socks, slippers/sandals, or shoes) could be documented. These falls were then independently evaluated by three additional assessors and a meeting was held to obtain consensus in relation to whether the footwear could have potentially contributed to the fall, and what mechanism may have been responsible. Cross-tabulations were performed in relation to footwear type and fall characteristics (proposed mechanism and fall direction). Results: There were 300 falls experienced by 118 older adults aged 58 years–98 years (mean age 82.8 years, SD 7.6). Of these falls, footwear could be ascertained in 224 (75%). After the consensus meeting, the proportion of falls considered to be potentially related to footwear was 40 (18%). The likelihood of footwear contributing to the fall was highest when participants were wearing socks (14/19 falls; 74% of all footwear-related falls), followed by being barefoot (2/6 falls; 33%), wearing slippers/sandals (17/100 falls; 17%), and wearing shoes (7/99 falls, 7%). Conclusion: Footwear could be a potential contributor to a substantial number of falls in residential aged care. Wearing socks would appear to place an older person at risk of future falls and should therefore be avoided in this population.
Ureterorenoscopic Stone Removal without Antibiotic Prophylaxis
Authors: Müller Maximilian Reinhard , Prey Eva-Maria , Spachmann Philipp Julian , Goßler Christopher , Burger Maximilian , Schnabel Marco Julius
Published: April 2024

Introduction: The aim of this study was to assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection undergoing ureterorenoscopy (URS) for stone removal. Methods: A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship. Patients with preoperative unremarkable urine culture received no antibiotic prophylaxis for URS stone removal (NoPAP). The NoPAP group was compared to a historic URS cohort, when antibiotic prophylaxis (PAP) was standard of care. Analysis focused on postoperative complications. Results: Postoperative fever occurred in 1% of the NoPAP and 2% of the PAP patients (p = 0.589). Clavien 1–3 complications did not differ between groups with 9% in the NoPAP and 6.2% in the PAP (p = 0.159). No Clavien 4–5 complications were seen. We identified a residual stone (p = 0.033) and an ASA score 3–4 (p = 0.004) as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis, the overall antibiotic usage was reduced from 100% (PAP) to 8.3% (NoPAP). Conclusion: Sparing a routine antibiotic prophylaxis during URS for stone removal seems feasible in patients with unremarkable preoperative urine culture for most of the patients. A prospective validation is warranted.
Mapeamento da Borda Sul-Sudeste da Bacia do Araripe com auxílio de gamaespectrometria e magnetometria
Authors: Aureliano Tito , Ghilardi Aline Marcele
Published: April 2024

The Araripe Basin is located on the border between the states of Pernambuco, Piauí and Ceará in Northeast Brazil, and presents a evolutionary classic model for understanding the Gondwana breakup events during the Cretaceous Period. Additionally, the basin also contains units of great paleontological and economic relevance. Most of the geological and paleontological studies conducted in the basin have focused on the northeastern margin of the basin, while the south and west still lack research. This study tested the application of gamma spectrometry and magnetometry for mapping the units in part of the south-southeastern border of the Araripe Basin. Three main units were identified in the region: the alluvial sandstones of the Exu Formation, the fossil-rich sandstones of the Missão Velha Formation, and the shales rich in fossiliferous calcareous concretions of the Romualdo Formation. It was possible to identify and individualize the Romualdo and Exu formations, and the basin contact with the basement with the support of geophysical data. Anomalies observed in radiometric data were used to map the lagerstatten unit, presenting a replicable model for other contexts and basins. Finally, the detailed geological survey showed that the Romualdo Formation is more extensive to the south than previously estimated, extending along the foot of the plateau with approximate E-W orientation.
Da imaterialidade cartesiana a materialidade Lamettriana da mente e sua relação com o corpo
Authors: Luchini Marcelo
Published: April 2024

Julien Offray de La Mettrie (1709-1751) médico e filósofo francês defendeu como conceito fundamental de sua filosofia a materialidade da alma, pois as discussões do século XVIII concernentes ao conhecimento humano e aos limites da experiência sensível impunham a necessidade de estudos aprofundados sobre a fisiologia dos sentidos e da sensibilidade. Para o médico-filosofo, o estudo do homem cuja estrutura e funcionamento dos nervos e do cérebro devem ser analisados em comparação com a dos animais a fim de tentar explicar a produção de pensamento se torna a hipótese mais produtiva, pois ao tomar a prática médica como guia, La Mettrie deseja realizar uma fusão entre a filosofia e a medicina. Ao descrever o homem analogamente a uma máquina, La Mettrie não reduz as propriedades "orgânicas" em propriedades "inorgânicas" e inversamente a fisiologia mecanicista de Descartes lança luz sobre uma questão fundamental, a relação entre corpo e alma – corpo e mente – ou seja, sobre o funcionamento do cérebro. A tentativa de explicar o funcionamento da mente em termos puramente materiais sem a necessidade da alma cartesiana, ou em outras palavras, demonstrar como o pensamento poderia ser o resultado de uma determinada organização da matéria no cérebro, se tornou a vertente da reflexão de sua filosofia e o aproximou da neurociencia moderna.
Maupertius e o pensamento evolutivo na época das luzes
Authors: Ramos Maurício de Carvalho
Published: April 2024

Pierre-Louis Moreau de Maupertuis viveu de 1698 a 1759, sendo o introdutor e um dos primeiros defensores das idéias de Newton na França. Sua fidelidade à filosofia natural newtoniana serviu como pano de fundo para a construção de uma sólida carreira científica e filosófica junto à Academia de Ciências de Paris. Além de seus estudos em geometria, deixou uma importante obra em física, cuja realização maior foi a formulação do princípio de mínima ação. Em astronomia, esteve à frente do combate entre os sistemas de mundo newtoniano e cartesiano, sendo responsável pela comprovação empírica do achatamento da Terra nos pólos.
Antiplatelet De-Escalation Strategies in Patients Undergoing Percutaneous Coronary Intervention
Authors: Spirito Alessandro , Krishnan Sriya L. , Capodanno Davide , Angiolillo Dominick J. , Mehran Roxana
Published: April 2024

Dual antiplatelet therapy—the combination of aspirin and a P2Y12 inhibitor—remains the standard antiplatelet regimen recommended to prevent ischemic complications immediately after percutaneous coronary intervention. Nonetheless, recent advances in stent technologies, percutaneous coronary intervention techniques, adjunctive pharmacotherapy for secondary prevention, and the rising awareness of the prognostic impact of bleeding, which are inevitably associated with dual antiplatelet therapy, led to the investigation of alternative antiplatelet regimens related to fewer bleeding and a preserved ischemic protection. Thrombotic complications occur mostly in the first months after percutaneous coronary intervention, while the risk of bleeding remains stable over time; this observation laid the foundation of the concept of antiplatelet de-escalation, consisting of a more intense antiplatelet regimen early after percutaneous coronary intervention, followed by a less potent antiplatelet therapy thereafter. According to new definitions proposed by the Academic Research Consortium, de-escalation can be achieved by discontinuation of 1 antiplatelet agent, switching from a potent P2Y12 inhibitor to clopidogrel, or by reducing the dose of antiplatelet agents. This review discusses the rationale and the evidence supporting antiplatelet de-escalation, provides practical guidance to use these new regimens, and gives insights into future developments in the field.
Ukraine and Violations of International Humanitarian Law – A Critical Analysis of the Amnesty International Report
Authors: Szpak Agnieszka
Published: April 2024

On 4 August 2022, Amnesty International published its report ‘Ukraine: Ukrainian Fighting Tactics Endanger Civilians’, in which it accused Ukraine of violating international humanitarian law ‘by establishing bases and operating weapons systems in populated residential areas, including in schools and hospitals’ and in this way putting civilians at risk. According to the report, ‘[s]uch tactics violate international humanitarian law and endanger civilians, as they turn civilian objects into military targets. The ensuing Russian strikes in populated areas have killed civilians and destroyed civilian infrastructure’. The report sparked some controversies. The question that the author attempts to answer in this article is whether there are any factual or legal arguments supporting the conclusions of the report.
Microfungi associated with dead caterpillars and spiders in Xishuangbanna Tropical Botanical Garden, P.R. China
Authors: YANG ER-FU , KARUNARATHNA SAMANTHA C. , PRIYASHANTHA ALVITI KANKANAMALAGE HASITH , PROMPUTTHA ITTHAYAKORN , CHEN XUEMEI , ELGORBAN ABDALLAH M. , BASHIR NAWAZ HAIDER , TIBPROMMA SAOWALUCK , DOSSA GBADAMASSI G. O.
Published: April 2024

During an investigation of microfungi associated with insects in the tropical region of Yunnan Province, China, dead fungi infected within several caterpillars and spiders in the Xishuangbanna Tropical Botanical Garden were found. Two selected fungal strains were isolated from the surface of the cadavers and subjected to morphological and molecular identification. Phylogenetic analyses were carried out on the subsequent isolates based on multiple gene sequences (ITS, LSU, SSU, rpb1, gapdh, and tef1-α). The observations and the analyses confirmed that the fungi belong to Curvularia geniculata (associated with dead caterpillars) and Purpureocillium atypicola (associated with dead spiders). Here, we have given detailed descriptions of the species along with photo plates and phylogenetic trees showing their taxonomic placements.