bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effectiveness of an Intensive Inpatient Psychotherapy Program for Chronic Depression: A naturalistic comparison with wait list
Authors: Eielsen Mikkel , Ulvenes Pål Gunnar , Røssberg Jan Ivar , Høstmælingen Andreas , Soma Christina S. , Wampold Bruce E.
Published: November 2022

Background

Patients with chronic depression (CD) typically have an early symptom onset, more psychiatric comorbidities, more treatment attempts, and more frequent and longer inpatient hospitalizations than patients with major depressive disorders. The main purpose of this study was to investigate the effectiveness of an intensive inpatient psychotherapy program for patients with chronic depression (CD). The primary research question was whether two intensive psychodynamic inpatient treatments, affect phobia therapy (APT) and VITA, were superior to an outpatient wait list condition, receiving treatment as usual (TAU), at completion of treatment. To investigate if a potential difference between the intensive treatment and the wait list control group was dependent on a specific psychotherapeutic model, the study contrasted two therapies with similar intensity, but different theoretical rationales.

Methods

Two hundred eighty patients with CD were included in a naturalistic study. Patients were assessed at four time points; assessment, start of therapy, end of therapy and 1-year follow-up. Three comparisons were performed with patients matched across groups; Intensive inpatient treatment program (APT + VITA) vs wait list during treatment, APT vs VITA during treatment and APT vs VITA during follow-up. The outcome measure was the BDI-II.

Results

Intensive inpatient treatment program vs. wait list showed a significant difference in favor of the intensive treatment. No significant differences were found between APT and VITA during therapy or follow-up; but both groups had large effect sizes during treatment, which were maintained during follow-up.

Conclusions

The intensive inpatient psychotherapy program showed superior effect on chronic depression over an outpatient wait list condition receiving treatment as usual (TAU), but no significant differences were found between the two intensive inpatient psychodynamic treatments. The results provide support for the effectiveness of an intensive inpatient psychotherapy program in treatment of chronic and severe disorders, such as CD, which could be of benefit for policymakers and the health care sector as they are allocating recourses efficiently.

Trial registration

This study has been retrospectively registered on ClinicalTrials.gov (NCT05221567) on February 3rd, 2022.
The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
Authors: Li Wenyan , Wang Wanxin , Lai Wenjian , Li Xiuwen , Zhu Liwan , Shi Jingman , Teopiz Kayla M. , McIntyre Roger S. , Guo Lan , Lu Ciyong
Published: November 2022

Background

Depressive symptoms among adolescents are a serious health concern around the world. Altered DNA methylation in the FK506 binding protein 5 (FKBP5) gene has been reported to regulate stress response, which has been reported to be closely associated with depressive symptoms. However, most of the contributing studies have been conducted among adults and relatively few studies have considered the effect of disparate social influences and sex differences on the DNA methylation of FKBP5 in persons with depressive symptoms. The present study aimed to test the associations of FKBP5 DNA methylation and depressive symptoms among adolescents and explore possible sex differences in the foregoing associations.

Methods

This study was conducted using a nested case-control design within a longitudinal cohort study from January 2019 to December 2019. Adolescents aged 12 to 17 years from 69 classes in 10 public high schools located in Guangdong province of China participated in this research. Students with persistent depressive symptoms that reported having depressive symptoms at both baseline and follow-up were treated as the case group, and those without depressive symptoms were randomly selected as the control group. Our study finally included 87 cases and 151 controls. Quantitative methylation analyses of the selected gene were carried out by MassARRAY platform System.

Results

The overall DNA methylation trend of FKBP5 CpG sites in the case group was lower in comparison to the control group. Compared to healthy controls, lower methylation percentage of FKBP5-12 CpG 1 was observed in adolescents with persistent depressive symptoms after adjusting for covariates (case: 0.94 ± 2.00, control: 0.47 ± 0.92; F = 5.41, P = 0.021), although the statistical significance of the difference was lost after false discovery rate correction (q > 0.05). In addition, the hypomethylation of FKBP5-12 CpG 1 was approaching significance after adjustment for social-environmental factors (aOR = 0.77; P = 0.055), which indicated that no independent association was detected between hypomethylation of FKBP5 CpG sites and persistent depressive symptoms. Furthermore, in the present study, we were unable to identify sex differences in the association of FKBP5 gene methylation with depressive symptoms.

Conclusion

The decreased methylation level of FKBP5 was observed in adolescents with persistent depressive symptoms, albeit non-significant after correction for multiple testing. Our results presented here are preliminary and underscore the complex gene-environment interactions relevant to the risk for depressive symptoms.
Distinct patterns of problematic smartphone use and related factors in Chinese college students
Authors: Hong Lan , Lai Xinyi , Xu Dongwu , Zhang Wei , Wu Bichang , Yu Xin , Zhao Ke , Zhang Guohua
Published: November 2022

Background

This study aimed to categorize different subgroups of problematic smartphone use in Chinese college students. Differences in gender and psychosocial characteristics of the categorized groups were also examined.

Methods

A total of 1123 participants completed the Mobile Phone Addiction Index Scale, the Center for Epidemiologic Studies Depression Scale, the Perceived Social Support Scale, and the Perceived Stress Scale. Using latent profile analysis, we identified different subgroups of problematic smartphone use in college students. Multivariate logistic regression analysis was implemented to examine the relationship between latent classes and demographic and psychosocial covariates.

Results

The four following latent classes were identified: a low-risk group, a moderate-risk with no evasiveness group, a moderate-risk with evasiveness group, and high-risk group that accounted for 11%, 24.1%, 35.5%, and 29.4% of the total sample, respectively. Further analysis revealed that female participants were more likely to be in the moderate-risk with evasiveness and high-risk groups, and individuals with depressed mood were more likely to be in the moderate-risk and high-risk groups.

Conclusions

Classifying college students according to the features of problematic smartphone use is potentially useful for understanding risk factors and developing targeted prevention and intervention programs.
Work after mental-health-related absence: a qualitative study of perceived change after a combination of metacognitive therapy and work-focused interventions
Authors: Bjørndal Marianne Tranberg , Giæver Fay , Aschim Bente Marianne , Gjengedal Ragne Gunnarsdatter Hole , Lending Hilde Dallavara , Bull-Hansen Bente , Hannisdal Marit , Hjemdal Odin
Published: November 2022

Background

Sick leave caused by common mental health disorders (CMD) is becoming more prevalent. For most people, work is essential for good mental and physical health. It is necessary to provide treatments that facilitate return to work (RTW) and a reduction of symptoms. A qualitative study can contribute to an understanding of what makes an intervention successful. The aim of this study was to investigate how individuals who are on sick leave because of CMD perceive and handle their symptoms and their work, after completing metacognitive therapy and work-focused interventions.

Methods

Semi-structured interviews were conducted with 23 participants after they had completed therapy. Thematic analysis was used to analyse the data.

Results

Through both therapy and the process of RTW, the participants had gained increased awareness and understanding of their mental health problems and the relationship between those problems and work. Together with the sense that they were in charge of their own process of RTW, this helped to improve their self-confidence. An important part of the process was the change to new strategies and the rejection of older maladaptive ones, in relation to both mental health and work. Being open about their mental illness in the workplace could lead to support but also to the opposite, and therefore not an option for everyone. After treatment, most had returned to work and gained a more positive outlook on the future, but some had less confidence in their ability to deal with future symptoms and workplace issues.

Conclusions

Achieving improved self-confidence and adopting new strategies, which enabled them to change how they related to their mental problems and how they addressed their problems at work, seemed to have increased their self-efficacy. Active involvement in therapy and at work was also important, both for the process and as a way of increasing self-efficacy. This gave them renewed belief in themselves and in their ability to handle their work at present and in the future. Despite this being a manualized treatment, the participants’ experience was that it was adapted to each individual, something they regarded as important.
The relationship between HIV pre-exposure prophylaxis, sexually transmitted infections, and antimicrobial resistance: a qualitative interview study of men who have sex with men
Authors: Williams Adam Dale Newman , Wood Fiona , Gillespie David , Couzens Zoë , Hughes Kathryn , Hood Kerenza
Published: November 2022

Background

HIV pre-exposure prophylaxis (PrEP) is a medication that prevents the acquisition of HIV. It has been targeted towards men who have sex with men (MSM). Since its introduction there have been concerns raised around changes in sexual behaviour such as increased condomless anal intercourse (CAI), leading to an elevation in sexually transmitted infections (STIs). With antimicrobial resistant strains of STIs rising, there are concerns that PrEP may be contributing to this growth. This study aims to understand how MSM conceptualise the relationship between PrEP, STIs and antimicrobial resistance (AMR).

Methods

Twenty semi-structured interviews were conducted online using Zoom. Participants include a mix of PrEP related experiences (never used, currently use, previously used). Reflexive thematic analysis was undertaken by the lead author with 10% of transcripts double coded.

Results

MSM in Wales have positive views and a good knowledge of PrEP and awareness of bacterial STIs. PrEP is perceived by many to lead to a reduction in condom use and increase in STIs but reported condom use behaviours presented to be stable in terms of PrEP initiation. PrEP use is influenced by increased concern for HIV and minimal concern for bacterial STIs. Awareness of AMR STIs was lacking.

Conclusions

There is a belief that PrEP use will lead to an increase in STI rates through reduced condom use, despite reported behaviours often being stable in relation to PrEP initiation, PrEP stigma may be influencing this dichotomy. Concern and awareness for resistant STIs is low, with little association to PrEP.
The impact of changing nonimmigrant visa policies on international students’ psychological adjustment and well-being in the United States during the COVID-19 pandemic: a qualitative study
Authors: Park Chulwoo , Shimada Shannon
Published: November 2022

Background

Since the Immigration and Nationality Act of 1952, the number of international students in the United States had been gradually increasing. However, the total numbers have begun to decrease since 2019–2020 school year due to the Trump administration's policy and COVID-19. Still, little is known about how international students’ psychological adjustment and well-being have been affected by changing nonimmigrant visa policy and the COVID-19 pandemic. 

Methods

We conducted a total of 34 online semi-structured in-depth interviews with international students from 18 countries of origin studying in the San Francisco Bay Area, California. More than 60% of the participants (21 out of 34) were aged 21 to 25. Among our 34 participants, gender and 18 were male and 16 were female, and 19 were undergraduate students and 15 were master’s students. The majority of the participants were first-generation college students (22/34, 64.71%). Verbatim transcription was done for all interviews. NVivo was used for both deductive and inductive approaches to the qualitative analysis.

Results

Overall, the recent political climate negatively impacted participants’ psychology of adjustment and well-being. July 6, 2020 Policy Directive for international students caused severe uncertainty about whether they can continue studying in the United States. There were many resources or services needed to overcome this period, such as extended mental and emotional support from the counseling services as well as financial and informational support from the international student office and university. Although international students had the benefit of the university's food assistance program, they were not eligible to receive any external support outside of the university and financial aid at the local and federal levels. Whether maintaining F-1 visa status was one of their major concerns. Due to COVID-19, job opportunities were limited, which made international students difficult to obtain Curricular Practical Training (CPT) and secure a job in the United States within the 90-day unemployment limit of Optical Practical Training (OPT). H-1B visa and permanent residency were other challenges to go through, but participants saw positive perspectives from the Biden administration.

Conclusions

Uncertain policy changes due to COVID-19 and presidential transitions impacted international students’ psychological well-being and adjustment. International students are important populations in the United States who have supported jobs that are high in demand and economically contributed to the United States. It is expected that future policies at various levels support international students’ life and improve their health equity and mental health.
A rare compound heterozygous EIF2AK4 mutation in pulmonary veno-occlusive disease
Authors: Zhang Chun , Du Qiang , Wang Sha , Zhang Ruifeng
Published: November 2022

Background

Pulmonary veno-occlusive disease (PVOD) is a rare, progressive, and oft-fatal condition of pulmonary arterial hypertension that is typically difficult to diagnose and treat. However, with the development of next-generation sequencing technology, an increasing number of patients with PVOD are being diagnosed.

Methods

Initially, we used whole exome sequencing (WES) to identify the proband as a rare compound heterozygous mutation of EIF2AK4 in PVOD. Subsequently, the parents of patient underwent EIF2AK4 screening by Sanger sequencing.

Results

In this study, we describe the family tree of a patient with PVOD with a rare compound heterozygous EIF2AK4 mutation. Moreover, we identified a new EIF2AK4 mutation, c.2236_2237insAAGTCCTTCT, in exon 12 of the proband and his mother. This frameshift mutation led to premature termination of the coding protein sequence and widespread loss of protein function, which promoted the development of PVOD.

Conclusions

Our results expand our understanding of the EIF2AK4 mutation spectrum in patients with PVOD, as well as highlight the clinical applicability of WES.
Transcorporeal decompression using a fully-endoscopic anterior cervical approach to treat cervical spondylotic myelopathy: surgical design and clinical application
Authors: Ma Yanyan , Xin Zhijun , Kong Weijun , Zhang Longsheng , Du Qian , Liao Wenbo
Published: November 2022

Background

Anterior cervical discectomy and fusion (ACDF) is a common procedure for treating cervical spondylotic myelopathy (CSM), however, ACDF may cause pseudoarthrosis, accelerated degeneration of adjacent segments, loss of activity of fused segments and other complications. The full-endoscopic technique can treat CSM, without the aforementioned complications above. Therefore, it is of great clinical value to investigate the surgical scheme of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC).

Methods

A total of 28 cases with single-segment Cervical spondylotic myelopathy (CSM) from April 2017 to July 2019 were involved in this study. The size of the disc-osteophyte complex was measured using imaging data prior to the operation. The diameter and direction of the bony passage was determined according to the size and central position of the complex, respectively. Twenty-eight patients underwent the above scheme for CSM. The clinical outcome evaluations included Visual Analog Scale (VAS) scores, Japanese Orthopedic Association (JOA) scores. The imaging assessment included MRI, CT and X-rays.

Results

The diameter of the designed bony passage was about 6.9 mm, and directed toward the lower edge of the diseased lower vertebral body oblique to the center of the disc-osteophyte complex. All patients successfully completed the operation. The postoperative neck pain VAS and JOA were significantly improved compared to preoperative values (p < 0.01). Postoperative MRI indicated complete decompression of the spinal cord. CT scanning 1 year after the operation revealed an almost healed bony passage and X-ray imaging showed satisfactory physiological curvature of the cervical spine, without cervical instability.

Conclusion

Based on the diameter and direction of the bony passage, as determined by the size and position of the disc-osteophyte complex, indicated by MRI and CT scanning, anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord offers good decompression of the spinal cord and ensures excellent therapeutic outcome.
Exploring facilitators and barriers to self-management engagement of Chinese people with type 2 diabetes mellitus and poor blood glucose control: a descriptive qualitative study
Authors: Liu Yuan , Jiang Jiajia , You Wenjun , Gong Dandan , Ma Xiaoqing , Wu Min , Li Feng
Published: November 2022

Aims

To explore facilitators and barriers to self-management engagement of Chinese people with poorly controlled type 2 diabetes.

Methods

Purposive sampling method was used for recruitment. Semi-structured interview and thematic analysis was used for data collection and analysis.

Results

Twenty-six semi-structured interviews were conducted. Poor blood glucose control introduced awareness of susceptibility to complications, while mental disorders could be concomitant. General knowledge about healthy lifestyle and unhealthy habits impeded lifestyle management. Temporary remission of hyperglycemia and no perceived symptoms interfered engagement of medication therapy and regular blood glucose monitoring. Family and work environments could impact self-management engagement. Accessibility to reliable diabetes-related information influenced self-management engagement.

Conclusions

Awareness of susceptibility to complications motivated self-management engagement, while the awareness could cause mental disorders that need to be addressed.

Customized lifestyle plans and behavior change technologies were crucial for lifestyle management. The progression of diabetes, importance of continuity of medication therapy, and the value of blood glucose monitoring should be clarified in diabetes education.

Building diabetes-friendly social environments and providing reliable diabetes-related information were essential.
Changes in launch delay and availability of pharmaceuticals in 30 European markets over the past two decades
Authors: Büssgen Melanie , Stargardt Tom
Published: November 2022

Background

The timing of the launch of a new drug is an important factor that determines access for patients. We evaluated patient access to pharmaceuticals in 30 European markets over the past two decades.

Methods

Launch dates were extracted from the IQVIA (formerly IMS) database for 30 European countries for all pharmaceuticals launched internationally between 2000 and 2017. We defined launch delay as the difference between the first international launch date and the corresponding national launch date, and calculated these for each country in our sample over time. Additionally, we ranked countries according to their launch delays and looked at changes in the ranking order over time. Lastly, we determined the availability of new pharmaceuticals in each country, calculating this as the percentage of these pharmaceuticals that were available in each country during a pre-specified interval.

Results

There was a clear trend towards a decrease in launch delays across all countries from 2000 (37.2 months) to 2017 (11.8 months). Over the entire observation period, the three fastest launching countries were the Netherlands, Sweden, and Germany, whereas the three slowest were Bosnia-Herzegovina, Serbia, and Turkey. Germany had the highest availability of new pharmaceuticals with 85.7%, followed by the United Kingdom (83.1%) and Norway (82.9%). Countries with the lowest availability of pharmaceuticals were Bosnia-Herzegovina, Serbia, and Latvia. Gross domestic product per capita was negatively correlated with launch delay (-0.67, p < 0.000) and positively correlated with the availability of pharmaceuticals (+ 0.19, p < 0.000).

Conclusion

Launch delay and the availability of pharmaceuticals varied substantially across all 30 European countries. Using countries with above-average availability and below-average launch delays as a benchmark, stakeholders may discuss or modify current pharmaceutical policy, if needed, to improve access to pharmaceutical care.
Retinal age gap as a predictive biomarker of stroke risk
Authors: Zhu Zhuoting , Hu Wenyi , Chen Ruiye , Xiong Ruilin , Wang Wei , Shang Xianwen , Chen Yifan , Kiburg Katerina , Shi Danli , He Shuang , Huang Yu , Zhang Xueli , Tang Shulin , Zeng Jieshan , Yu Honghua , Yang Xiaohong , He Mingguang
Published: November 2022

Background

The aim of this study is to investigate the association of retinal age gap with the risk of incident stroke and its predictive value for incident stroke.

Methods

A total of 80,169 fundus images from 46,969 participants in the UK Biobank cohort met the image quality standard. A deep learning model was constructed based on 19,200 fundus images of 11,052 disease-free participants at baseline for age prediction. Retinal age gap (retinal age predicted based on the fundus image minus chronological age) was generated for the remaining 35,917 participants. Stroke events were determined by data linkage to hospital records on admissions and diagnoses, and national death registers, whichever occurred earliest. Cox proportional hazards regression models were used to estimate the effect of retinal age gap on risk of stroke. Logistic regression models were used to estimate the predictive value of retinal age and well-established risk factors in 10-year stroke risk.

Results

A total of 35,304 participants without history of stroke at baseline were included. During a median follow-up of 5.83 years, 282 (0.80%) participants had stroke events. In the fully adjusted model, each one-year increase in the retinal age gap was associated with a 4% increase in the risk of stroke (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.00–1.08, P = 0.029). Compared to participants with retinal age gap in the first quintile, participants with retinal age gap in the fifth quintile had significantly higher risks of stroke events (HR = 2.37, 95% CI: 1.37–4.10, P = 0.002). The predictive capability of retinal age alone was comparable to the well-established risk factor-based model (AUC=0.676 vs AUC=0.661, p=0.511).

Conclusions

We found that retinal age gap was significantly associated with incident stroke, implying the potential of retinal age gap as a predictive biomarker of stroke risk.
Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine
Authors: Lovell Jonathan F. , Baik Yeong Ok , Choi Seuk Keun , Lee Chankyu , Lee Jeong-Yoon , Miura Kazutoyo , Huang Wei-Chiao , Park Young-Shin , Woo Sun-Je , Seo Sang Hwan , Kim Jae-Ouk , Song Manki , Kim Chung-Jong , Choi Jae-Ki , Kim Jieun , Choo Eun Ju , Choi Jung-Hyun
Published: November 2022

Background

Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes.

Methods

Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19–75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT).

Results

Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization.

Conclusions

ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway.

Trial registration

The trial was registered at ClinicalTrials.gov as # NCT04783311.
The developmental miR-17–92 cluster and the Sfmbt2 miRNA cluster cannot rescue the abnormal embryonic development generated using obstructive epididymal environment-producing sperm in C57BL/6 J mice
Authors: Wu Xunwei , He Xiaomei , Liu Qian , Li Honggang
Published: November 2022

Background

Sperm, during epididymal transit, acquires microRNAs(miRNAs), which are crucial for embryonic development. However, whether sperm miRNAs influenced by an obstructive epididymal environment affect embryonic development remains unknown.

Method

The sham operation and vasectomy were performed in C57BL/6 J mice to create the control group (CON) and the obstructive epididymal environment group(OEE) group, respectively. The morphology of the testis and epididymis was observed using hematoxylin and eosin staining (HE staining) to establish the OEE mice model. The sperm quality test, intracytoplasmic sperm injection (ICSI), and epididymosomes fusion were employed to observe the effect of the obstructive epididymal environment on sperm and resultant embryonic development. The alteration of the sperm small RNA (sRNA) profile was analyzed by sRNA sequencing. RT-qPCR and DNA methylation were applied to observe the effect of obstructive epididymis on the expression of sperm miRNAs. The miRNAs microinjection was used to explore the impacts of sperm miRNAs on embryonic development.

Results

We confirmed postoperative 8-week mice as the OEE mice model by examining the morphology of the testis and epididymis. In the OEE group, we observed that sperm quality degraded and the development potential of embryos was reduced, which can be saved by the normal epididymal environment. The sperm sRNA sequencing revealed that the expression of the developmental miR-17–92 cluster and the Sfmbt2 miRNA cluster was downregulated in the OEE group. The expression of these two miRNA clusters in epididymis was also downregulated and regulated by DNA methylation. However, the downregulation of either the miR-17–92 cluster or the Sfmbt2 miRNA cluster in normal zygotes did not impair embryonic development.

Conclusion

The obstructive epididymal environment influences sperm quality and resultant embryonic development, as well as the abundance of the developmental miR-17–92 cluster and the Sfmbt2 miRNA cluster in sperm, but these miRNA clusters are not the cause of abnormal embryonic development. It implies that epididymis is important in early embryonic development and may play a potential role in sperm epigenome.
Atrial fibrillation and anticoagulation are associated with hospitalisations in patients with end-stage kidney disease on haemodialysis: a prospective population-based cohort study
Authors: Steiner Daniel , Schmaldienst Sabine , Lorenz Matthias , Klauser-Braun Renate , Pabinger Ingrid , Ay Cihan , Säemann Marcus , Königsbrügge Oliver
Published: November 2022

Background

Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity amongst patients on haemodialysis. We aimed to assess frequency, reasons, and duration of hospitalisations in haemodialysis patients and their association with atrial fibrillation and anticoagulation.

Methods

Prevalent patients with end-stage kidney disease on haemodialysis were recruited into a prospective cohort study and observed for a median observation time of 3.4 years. Hospitalisations were recorded from discharge letters, medical records, and patient interviews. The association of atrial fibrillation, anticoagulation, and time-in-therapeutic range of vitamin K antagonist treatment with hospitalisations was analysed using negative binomial regression.

Results

Out of 625 patients, 238 (38.1%) had atrial fibrillation. Median number of hospitalisations per patient was 3.0 (1.0–5.0). Incidence rate of hospitalisation was 1.7 per patient-year in all and 1.9 in atrial fibrillation patients, median duration per hospitalisation was 7.9 (4.8–12.9) and 8.8 (5.7–13.3) days, respectively. Most frequent reasons for hospitalisation were vascular access complication/intervention (11.7%) and infection/fever (11.4%), while bleeding events comprised 6.0% of all hospitalisations. Atrial fibrillation patients had 27% higher risk of hospitalisation than patients without atrial fibrillation (incidence rate ratio [IRR] 1.27, 95% confidence interval [CI] 1.10–1.47). In atrial fibrillation patients, anticoagulation (enoxaparin or phenprocoumon, 41.6% of AF patients) was associated with increased risk of all-cause (IRR 1.38, 95%CI 1.14–1.69) and bleeding-related hospitalisation (IRR 1.96, 95%CI 1.06–3.63). There was no association between anticoagulation and stroke-related hospitalisation. In atrial fibrillation patients on phenprocoumon, increasing time-in-therapeutic range was associated with decreased risk of all-cause (IRR 0.35, 95%CI 0.14–0.87), but not bleeding-related hospitalisation (IRR 0.13, 95%CI 0.01–1.38).

Conclusion

In haemodialysis patients, presence of atrial fibrillation and, among those with atrial fibrillation, anticoagulation were associated with higher risk of all-cause hospitalisation, including bleeding-related hospitalisation in the latter. Increasing time-in-therapeutic range in patients on vitamin K antagonist treatment was associated with decreased risk of all-cause, but not bleeding-related hospitalisation.
Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study
Authors: Gu Juanjuan , Ternifi Redouane , Sabeti Soroosh , Larson Nicholas B. , Carter Jodi M. , Fazzio Robert T. , Fatemi Mostafa , Alizad Azra
Published: November 2022

Background

There is a strong correlation between the morphological features of new tumor vessels and malignancy. However, angiogenic heterogeneity necessitates 3D microvascular data of tumor microvessels for more reliable quantification. To provide more accurate information regarding vessel morphological features and improve breast lesion characterization, we introduced a quantitative 3D high-definition microvasculature imaging (q3D-HDMI) as a new easily applicable and robust tool to morphologically characterize microvasculature networks in breast tumors using a contrast-free ultrasound-based imaging approach.

Methods

In this prospective study, from January 2020 through December 2021, a newly developed q3D-HDMI technique was evaluated on participants with ultrasound-identified suspicious breast lesions recommended for core needle biopsy. The morphological features of breast tumor microvessels were extracted from the q3D-HDMI. Leave-one-out cross-validation (LOOCV) was applied to test the combined diagnostic performance of multiple morphological parameters of breast tumor microvessels. Receiver operating characteristic (ROC) curves were used to evaluate the prediction performance of the generated pooled model.

Results

Ninety-three participants (mean age 52 ± 17 years, 91 women) with 93 breast lesions were studied. The area under the ROC curve (AUC) generated with q3D-HDMI was 95.8% (95% CI 0.901–1.000), yielding a sensitivity of 91.7% and a specificity of 98.2%, that was significantly higher than the AUC generated with the q2D-HDMI (p = 0.02). When compared to q2D-HDMI, the tumor microvessel morphological parameters obtained from q3D-HDMI provides distinctive information that increases accuracy in differentiating breast tumors.

Conclusions

The proposed quantitative volumetric imaging technique augments conventional breast ultrasound evaluation by increasing specificity in differentiating malignant from benign breast masses.
SIEVE: joint inference of single-nucleotide variants and cell phylogeny from single-cell DNA sequencing data
Authors: Kang Senbai , Borgsmüller Nico , Valecha Monica , Kuipers Jack , Alves Joao M. , Prado-López Sonia , Chantada Débora , Beerenwinkel Niko , Posada David , Szczurek Ewa
Published: November 2022

We present SIEVE, a statistical method for the joint inference of somatic variants and cell phylogeny under the finite-sites assumption from single-cell DNA sequencing. SIEVE leverages raw read counts for all nucleotides and corrects the acquisition bias of branch lengths. In our simulations, SIEVE outperforms other methods in phylogenetic reconstruction and variant calling accuracy, especially in the inference of homozygous variants. Applying SIEVE to three datasets, one for triple-negative breast (TNBC), and two for colorectal cancer (CRC), we find that double mutant genotypes are rare in CRC but unexpectedly frequent in the TNBC samples.
MoDLE: high-performance stochastic modeling of DNA loop extrusion interactions
Authors: Rossini Roberto , Kumar Vipin , Mathelier Anthony , Rognes Torbjørn , Paulsen Jonas
Published: November 2022

DNA loop extrusion emerges as a key process establishing genome structure and function. We introduce MoDLE, a computational tool for fast, stochastic modeling of molecular contacts from DNA loop extrusion capable of simulating realistic contact patterns genome wide in a few minutes. MoDLE accurately simulates contact maps in concordance with existing molecular dynamics approaches and with Micro-C data and does so orders of magnitude faster than existing approaches. MoDLE runs efficiently on machines ranging from laptops to high performance computing clusters and opens up for exploratory and predictive modeling of 3D genome structure in a wide range of settings.
Isolation and production optimization of a novel milk-clotting enzyme Bacillus velezensis DB219
Authors: Zhang Yao , Hu Jiayun , Liu Xiaofeng , Jiang Chunmin , Sun Juan , Song Xinjie , Wu Yuanfeng
Published: November 2022

The milk-clotting enzyme (MCE) is a crucial ingredient in cheese manufacture. Due to the limits of traditional MCE, finding viable substitute is a pressing issue. This study aims to isolate and identify a wild strain with high milk-clotting activity (MCA) and low proteolytic activity (PA) and optimize the fermentation conditions for MCE production. A strain of Bacillus velezensis DB219 with high MCA/PA value (9.2) was isolated from dairy soil (Wuchang, Heilongjiang, China) and identified through 16S rRNA from 40 strains. The optimal wheat bran, carbon, nitrogen, inoculum size, volume and initial pH were 60 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, 5%, 40 mL and 6.15, respectively for improving DB219 MCE production through single factor experiment. The wheat bran concentration, corn steep liquor concentration and volume were the most critical factor and their changed range was determined through Plackett–Burman design and the steepest ascent/descent experiments. The response surface analysis experiment of three factors and three levels was conducted by Box–Behnken design. The theoretical optimal fermentation conditions for DB219 MCE were as follows: wheat bran concentration 60.14 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, inoculum size 5%, volume 40.08 mL and initial pH 6.15. DB219 MCE achieved the maximal MCA (3164.84 SU/mL) that was 101.9% of the predicted value (3104.49 SU/mL) and 4.3-fold higher than the control.
Identification and characterization of drought-induced long noncoding RNAs (DRILs) in rice
Authors: Oh Nuri , Seo Jun Sung , Chung Pil Joong , Lee Jimin , Seo Jang-Kyun , Kang Jin-Ho , Cho Hye Sun , Jung Choonkyun
Published: November 2022

Long noncoding RNAs (lncRNAs) act as transcriptional regulators in plants and animals. To date, they have been reported to regulate various biological processes, such as phosphate homeostasis, grain yield, and fertility in rice (Oryza sativa L.). However, the lncRNAs involved in abiotic stress responses remain poorly identified in rice. In this study, we analyzed the expression profiles of lncRNAs using public rice transcriptome datasets derived from abiotic stress-treated samples. We found that the expression of thousands of rice lncRNAs was significantly altered in the shoot and root tissues under different abiotic stresses (drought, high salinity, low temperature, and abscisic acid). We selected six novel drought-induced lncRNAs (DRILs, specifically DRIL1 to DRIL6) for further study. Real-time polymerase chain reaction analysis revealed the differential expression patterns of these DRILs under various stress conditions. The expression of abiotic stress-responsive genes was upregulated in the protoplasts by transiently overexpressed DRIL1 and DRIL4. Therefore, DRILs may be involved in the transcriptional regulation of abiotic stress-responsive genes in rice.
Somatic copy number variant load in neurons of healthy controls and Alzheimer’s disease patients
Authors: Turan Zeliha Gözde , Richter Vincent , Bochmann Jana , Parvizi Poorya , Yapar Etka , Işıldak Ulas , Waterholter Sarah-Kristin , Leclere-Turbant Sabrina , Son Çağdaş Devrim , Duyckaerts Charles , Yet İdil , Arendt Thomas , Somel Mehmet , Ueberham Uwe
Published: November 2022

The possible role of somatic copy number variations (CNVs) in Alzheimer’s disease (AD) aetiology has been controversial. Although cytogenetic studies suggested increased CNV loads in AD brains, a recent single-cell whole-genome sequencing (scWGS) experiment, studying frontal cortex brain samples, found no such evidence. Here we readdressed this issue using low-coverage scWGS on pyramidal neurons dissected via both laser capture microdissection (LCM) and fluorescence activated cell sorting (FACS) across five brain regions: entorhinal cortex, temporal cortex, hippocampal CA1, hippocampal CA3, and the cerebellum. Among reliably detected somatic CNVs identified in 1301 cells obtained from the brains of 13 AD patients and 7 healthy controls, deletions were more frequent compared to duplications. Interestingly, we observed slightly higher frequencies of CNV events in cells from AD compared to similar numbers of cells from controls (4.1% vs. 1.4%, or 0.9% vs. 0.7%, using different filtering approaches), although the differences were not statistically significant. On the technical aspects, we observed that LCM-isolated cells show higher within-cell read depth variation compared to cells isolated with FACS. To reduce within-cell read depth variation, we proposed a principal component analysis-based denoising approach that significantly improves signal-to-noise ratios. Lastly, we showed that LCM-isolated neurons in AD harbour slightly more read depth variability than neurons of controls, which might be related to the reported hyperploid profiles of some AD-affected neurons.
Evaluation of a skills-based peer-led art therapy online-group for people with emotion dysregulation
Authors: Jewell Mahlie , Bailey Rachel C , Curran Renae L , Grenyer Brin F.S.
Published: November 2022

Objective

We developed and piloted a novel art-based online skills program led by a peer mental health professional with lived experience of complex mental health, including Borderline Personality Disorder (BPD). Key challenges of living with BPD and emotion dysregulation were addressed through artmaking informed by a dialectical framework and skills, to evaluate acceptability and efficacy.

Method

A structured, manualised 2-hour weekly arts-based skills program was piloted for people with BPD over 18 weeks. Evaluation included both quantitative and qualitative measures at commencement and completion.

Results

Thirty-eight participants enrolled in the program (89.5% identified she/her pronouns, average age 33.6 years), and 31 completed (82% retention). Multilevel modelling analysis of the primary outcome variable Difficulties in Emotion Regulation Scale (DERS) demonstrated a large improvement over time (effect size Cohen’s d = 1.77). Qualitative thematic analysis found participants had improved capacity to regulate emotions and tolerate distress, improved connection with others, enhanced understanding of the self, and higher hope for living well. We found that artmaking facilitated processes and helped the expression of difficult emotions, symbolise challenging relationships, and facilitate greater self-understanding. Participants reported high levels of satisfaction, and 77.4% reported that the program had increased wellbeing.

Conclusion

This novel artmaking program for emotion dysregulation and BPD was acceptable and potentially effective. Peer facilitation using arts-based skills is a modality of therapy for further investigation.
Decision support system for handling control decisions and decision-maker related to supply chain
Authors: Alahmadi Dimah Hussein , Jamjoom Arwa A.
Published: November 2022

Background

The present study presents a knowledge-based DSS framework for supporting the decision-maker and handling control decisions related to supply chains.

Methods

Two binary variables were adopted for denoting at which time point a given task$$i$$istarts and finishes. The scheduling issues are represented through the ontological model and appropriately interpreted using the Java environment. Regarding primary data, digital form of administration using google form platform took precedence over physical administration.

Results

The findings might not be exact replication of the findings from previous studies that are limited to the influence of information and material flow on the performance of supply chain as there are concerns of what factors constitute information and material flow that need to be identified and considered. However, with the finding of associating factors of information and material flow may need to consider this in managing the flow and the supply chain. Associating factors such as information quality, information visibility, material cost, fund shortage and so on, play a role in information and material flow and the decisions made in an organization.

Conclusions

Factors associating with information and material flow need to be considered in decision making as well, as the cost in any of the elements affects the flow and this would impede supply chain performance of the organization.
Efficient 1,3-dihydroxyacetone biosynthesis in Gluconobacter oxydans using metabolic engineering and a fed-batch strategy
Authors: Zeng Weizhu , Shan Xiaoyu , Liu Li , Zhou Jingwen
Published: November 2022

1,3-Dihydroxyacetone (DHA) is a commercially important chemical and widely used in cosmetics, pharmaceuticals, and food industries as it prevents excessive water evaporation, and provides anti-ultraviolet radiation protection and antioxidant activity. Currently, the industrial production of DHA is based on a biotechnological synthetic route using Gluconobacter oxydans. However, achieving higher production requires more improvements in the synthetic process. In this study, we compared DHA synthesis levels in five industrial wild-type Gluconobacter strains, after which the G. oxydans WSH-003 strain was selected. Then, 16 dehydrogenase genes, unrelated to DHA synthesis, were individually knocked out, with one strain significantly enhancing DHA production, reaching 89.49 g L−1 and 42.27% higher than the wild-type strain. By optimizing the culture media, including seed culture and fermentation media, DHA production was further enhanced. Finally, using an established fed-batch fermentation system, DHA production reached 198.81 g L−1 in a 5 L bioreactor, with a glycerol conversion rate of 82.84%.

Graphical Abstract
Developing and testing the ExerciseGuide UK website for people with lung cancer: reflections on the added value of patient and public involvement within a doctoral degree
Authors: Curry Jordan , Roberts Helen , Smith Alan , Riley Diane , Pearson Mark , Forbes Cynthia C.
Published: November 2022

Background

Lung cancer has one of the highest incidence and mortality rates worldwide. Physical activity can provide those diagnosed with lung cancer with several physical and psychological benefits. However, the examination of digitally delivered physical activity to those with lung cancer is not as researched as other common cancers. Often, those diagnosed with lung cancer are older adults (65 years or older). Older adults are often wrongly assumed to lack digital skills, interest, and not engage with digital technology regularly. Although individuals are interested, would involving older people in designing of websites and apps result in better engagement?

Main body

In this article, the authors discuss the process of adapting a digital platform with a patient and public involvement group to provide those who have received a lung cancer diagnosis with a tailored physical activity program and health educational modules. We discuss the influence of recurrent patient and public involvement on the study, the patient and public involvement members, and the doctoral researcher.

Conclusion

Working with a patient and public involvement group over several months, especially potential users of a digital intervention, may enhance its relevance, accessibility, and usability. By engaging with patients, family, or caregivers for someone with lung cancer, the doctoral student gained insight into the needs of the study population and what to consider during development. All group members expressed their interest and enjoyment in their involvement, and several are now active members of a wider patient and public involvement network.