bluuebunny/crossref_metadata_2025 huggingface dataset:
Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3–MAPK Signaling to Trigger Spontaneous Aortic Dissection
Authors: Zhang Ting-Ting , Lei Qing-Qing , He Jie , Guan Xin , Zhang Xin , Huang Ying , Zhou Zi-Yue , Fan Rui-Xin , Wang Ting , Li Chen-Xi , Shang Jin-Yan , Lin Zhuo-Miao , Peng Wan-Li , Xia Li-Kai , He Yu-Ling , Hong Chuan-Ying , Ou Jing-Song , Pang Rui-Ping , Fan Xiao-Ping , Huang Hui , Zhou Jia-Guo
Published: May 2023

BACKGROUND:

Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive.

METHODS:

Smooth muscle cell–specific and endothelial cell–specific Best3 knockout mice (Best3
SMKO
and Best3
ECKO
, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels.

RESULTS:

Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3
SMKO
but not Best3
ECKO
mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II–infused Best3
SMKO
and ApoE
−/−
mice.

CONCLUSIONS:

These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3–MEKK2/3 signaling represents a novel therapeutic target for AD.
Identifying Hate Speech Trends and Prevention in Indonesia: a Cross-Case Comparison
Authors: Alexandra Lina A. , Satria Alif
Published: May 2023

This article provides an analysis on Indonesia’s hate speech phenomenon within the past two decades. It identifies shared characteristics across hate speech campaigns and how state and non-state actors have addressed them. In doing so, the article compares three campaigns targeting: the Ahmadiyya (2005–2011), Shi’a (2006–2012) and Jakarta’s Chinese Christian Governor Basuki Tjahaja Purnama (2016–2017). It finds that despite their unique dynamics, each campaign shared several commonalities. They were enabled by rising religious conservatism, sustained support from politicians, and competition for socio-economic capital; their framing strategy similarly used a threat-to-survival narrative, leveraged state regulations, and involved amplifying their voices through online spaces; and they had similar long-term impact which, despite an absence of mass violence, normalised the deprivation of vulnerable minorities’ fundamental rights.
Lathyrus turcicus (Fabeae, Fabaceae), a new species from Northwestern Türkiye
Authors: HAMZAOĞLU ERGİN
Published: May 2023

Some interesting Lathyrus (Fabaceae) specimens were collected from Büyükorhan District in Bursa Province, N.W. Türkiye. The specimens, at first glance, resembled the Lathyrus pallescens (sect. Platystylis) species as a habit, which grows in N. Balkans, Hungary, Romania, C. & S. Russia, Crimea, Transcaucasica and N.E. Türkiye. However, as a result of detailed examination, it was determined that there were some differences. Based on these differences, the specimens were presented to the scientific world as a new species and were named Lathyrus turcicus. The fact that the stipules are shorter than petiole (not longer than petiole); the calyces are glabrous (not hairy); the calyx teeth subequal (not unequal); the standards and wings are almost equal and 13.2–15.3 mm long (not 20–24 mm); the keels 11–13 mm long (not 16–18 mm) and the legumes 7–9 mm wide (not 3–5 mm) are the most obvious attributes that separate Lathyrus turcicus from L. pallescens, that is a close species. Here, a description of the new species, supporting images, chorology, and general ecological preferences were given.
A new synonym of Bathseba Motschulsky, 1866 (Chrysomelidae, Eumolpinae, Typophorini) with a new species and redescription of B. bifasciata (Jacoby, 1895) n. comb. and other taxonomic and biological notes
Authors: KUMARI AMRITHA , MOSEYKO S. A. G. , PRATHAPAN K. D.
Published: May 2023

Tricliona Lefèvre, 1885 n. syn. is a new junior synonym of Bathseba Motschulsky, 1866. Bathseba syzygium n. sp., a pest of Syzygium cumini (L.) Skeels (Myrtaceae) in south India, is described and illustrated. Bathseba bifasciata (Jacoby, 1895) n. comb. is redescribed and illustrated. Bathseba bengalensis (Jacoby, 1908) n. syn. is synonymized with B. indica (Jacoby, 1900). Cleoporus variegatus Jacoby, 1904 is transferred to Bathseba and Tricliona subdepressa Jacoby, 1908 n. syn. is treated as its synonym. Tricliona foveipennis Bryant, 1950 is transferred to Gressittella Medvedev, 2009. Mangifera indica L. and Anacardium occidentale L. (both Anacardiaceae) are reported as host plants of B. bifasciata for the first time.
Repression of TRIM13 by chromatin assembly factor CHAF1B is critical for AML development
Authors: Dean Sarai T. , Ishikawa Chiharu , Zhu Xiaoqin , Walulik Sean , Nixon Timothy , Jordan Jessica K. , Henderson Samantha , Wyder Michael , Salomonis Nathan , Wunderlich Mark , Greis Kenneth D. , Starczynowski Daniel T. , Volk Andrew G.
Published: May 2023

Acute myeloid leukemia (AML) is an aggressive blood cancer that stems from the rapid expansion of immature leukemic blasts in the bone marrow. Mutations in epigenetic factors represent the largest category of genetic drivers of AML. The chromatin assembly factor CHAF1B is a master epigenetic regulator of transcription associated with self-renewal and the undifferentiated state of AML blasts. Upregulation of CHAF1B, as observed in almost all AML samples, promotes leukemic progression by repressing the transcription of differentiation factors and tumor suppressors. However, the specific factors regulated by CHAF1B and their contributions to leukemogenesis are unstudied. We analyzed RNA sequencing data from mouse MLL-AF9 leukemic cells and bone marrow aspirates, representing a diverse collection of pediatric AML samples and identified the E3 ubiquitin ligase TRIM13 as a target of CHAF1B-mediated transcriptional repression associated with leukemogenesis. We found that CHAF1B binds the promoter of TRIM13, resulting in its transcriptional repression. In turn, TRIM13 suppresses self-renewal of leukemic cells by promoting pernicious entry into the cell cycle through its nuclear localization and catalytic ubiquitination of cell cycle–promoting protein, CCNA1. Overexpression of TRIM13 initially prompted a proliferative burst in AML cells, which was followed by exhaustion, whereas loss of total TRIM13 or deletion of its catalytic domain enhanced leukemogenesis in AML cell lines and patient-derived xenografts. These data suggest that CHAF1B promotes leukemic development, in part, by repressing TRIM13 expression and that this relationship is necessary for leukemic progression.
Uveitis including Vogt-Koyanagi-Harada syndrome following inactive covid-19 vaccination: a case series
Authors: Shariati Mehrdad Motamed , Abrishami Mojtaba , Jahani Shahin , Bolouki Ali , Ansari-Astaneh Mohamad-Reza , Hosseini Seyedeh Maryam
Published: May 2023

Background

Currently, large populations have been vaccinated against COVID-19. The whole inactivated Sinopharm COVID-19 vaccine has been the main available COVID-19 vaccine in Iran. Ocular inflammatory reactions have been reported following vaccination. The present case reports aim to introduce four cases of uveitis after the Sinopharm vaccine administration.

Case presentation

Our first reported case is a 38-year-old woman with a positive medical history of inactive ulcerative colitis. Active uveitis had developed following the second dose of the COVID-19 vaccination. The remaining three cases were healthy individuals who developed the first episode of uveitis, after the COVID-19 vaccine administration. Vogt-Koyanagi-Harada syndrome was the final diagnosis in one of the aforementioned cases. All four patients demonstrated favorable responses to corticosteroid treatment.

Conclusion

These observations are in line with incoming reports from all around the world and raise concerns about the possibility of post-vaccination uveitis development, especially in cases with a previous history of auto-immune systemic diseases or inactive uveitis.
Establishment and validation of the autophagy-related ceRNA network in irreversible pulpitis
Authors: Wang Ye , Xie Qiuyan , Yu Hongwen , Zhou Bangyi , Guo Xiaolan , Wu Buling , Hu Jiao
Published: May 2023

Background

The molecular mechanisms underlying the onset and progression of irreversible pulpitis have been studied for decades. Many studies have indicated a potential correlation between autophagy and this disease. Against the background of ﻿the competing endogenous RNA (ceRNA) theory, protein-coding RNA functions are linked with long ﻿noncoding RNAs (lncRNAs) and microRNAs (miRNAs). This mechanism has been widely studied in various fields but has rarely been reported in the context of irreversible pulpitis. The hub genes selected under this theory may represent the key to the interaction between autophagy and irreversible pulpitis.

Results

Filtering and differential expression analyses of the GSE92681 dataset, which contains data from 7 inflamed and 5 healthy pulp tissue samples, were conducted. The results were intersected with autophagy-related genes (ARGs), and 36 differentially expressed ARGs (DE-ARGs) were identified. Functional enrichment analysis and construction of the protein‒protein interaction (PPI) network of DE-ARGs were performed. Coexpression analysis was conducted between differentially expressed lncRNAs (DElncRNAs) and DE-ARGs, and 151 downregulated and 59 upregulated autophagy-related DElncRNAs (AR-DElncRNAs) were identified. StarBase and multiMiR were then used to predict related microRNAs of AR-DElncRNAs and DE-ARGs, respectively. We established ceRNA networks including 9 hub lncRNAs (HCP5 and AC112496.1 ↑; FENDRR, AC099850.1, ZSWIM8-AS1, DLX6-AS1, LAMTOR5-AS1, TMEM161B-AS1 and AC145207.5 ↓), which were validated by a qRT‒PCR ﻿analysis of pulp tissue from patients with irreversible pulpitis.

Conclusion

We constructed two networks consisting of 9 hub lncRNAs based on the comprehensive identification of autophagy-related ceRNAs. This study may provide novel insights into the interactive relationship between autophagy and irreversible pulpitis and identifies several lncRNAs that may serve as potential biological markers.
Optimal method for ablation of atypical AVNRT
Authors: Aslani Amir , Shahrzad Shahab , Bazrafshan Mehdi , Rahmanian Mahdi , Fakhar Reza , Pirahesh Kasra , bazrafshan Hanieh , Bazrafshan Hamed
Published: May 2023

Background

Considering that ablation of atypical AVNRT may be unsuccessful after ablation at the right posterior septum, in this study, we aimed to present an optimal method for ablation of atypical AVNRT. Also, we evaluated the efficacy of this technique for preventing recurrences.

Methods

This is a prospective, double-center study. It was conducted on 62 patients with atypical AVNRT referred for radiofrequency ablation. The patients were randomly divided into two groups before ablation: 1-Group A (n = 30): treated with conventional ablation at the anatomic area of the slow pathway; 2-Group B (n = 32): ablation was done 2 mm higher in the septum during fluoroscopy.

Results

The mean age of patients in groups A and B were 54 ± 11.7 and 55 ± 12.2, respectively (P = 0.43). In group A, ablation was successful in 24 (80%) patients following right-sided slow pathway ablation, and the remaining patients required further treatment with either a left-side approach (N = 4, 13.3%) or ablation of additional regions (N = 2, 6.7%). In group B, ablation was successful in all patients. After a 48-month follow-up, recurrence of symptomatic atypical AVNRT was detected in 4 (13.3%) patients of group A and none of group B patients (p < 0.001).

Conclusion

In patients with atypical AVNRT, ablation 2 mm above the conventional area is more promising regarding success rate and recurrence of the arrhythmia.
Effects of Taiwan’s COVID-19 alert levels on the physical activity behaviors and psychological distress of community-dwelling older adults
Authors: Lin Wang-Sheng , Tsai Chih-Chun , Pan Po-Jung
Published: May 2023

Background

The Taiwanese government implemented stringent preventative health measures to curb the spread of COVID-19. However, these measures negatively affected the physical activity behaviors and psychological distress of individuals. In this study, we investigated the effects of Taiwan’s COVID-19 alert–based restrictions on the physical activity behaviors and psychological distress of community-dwelling older adults.

Methods

In this longitudinal study, 500 community-dwelling older adults were randomly sampled from a health promotion center in Taiwan. Telephone interviews were conducted between May 11, 2021, and August 17, 2021, which coincided with the Level 3 alert period when group physical activities were prohibited. Telephone interviews were again conducted between June 20, 2022, and July 4, 2022, after the alert level was reduced to Level 2 but group physical activities were prohibited period. Through the telephone interviews, data regarding the participants’ physical activity behaviors (type and amount) and 5-item Brief Symptom Rating Scale (BSRS-5) scores were collected. Moreover, data regarding physical activity behaviors were collected from the records of our previous health promotion programs, which were conducted before the national alert period. The obtained data were analyzed.

Results

The alert levels influenced physical activity behaviors. Because of strict regulations, physical activity amount decreased during the Level 3 alert period and did not recover rapidly during the Level 2 alert period. Instead of engaging in group exercises (e.g., calisthenics and qigong), the older adults chose to exercise alone (e.g., strolling, brisk walking, and biking). Our findings indicate that the COVID-19 alert level has a significant influence on the amount of physical activity for participants (p < 0.05, partial η2 = 0.256), with pairwise comparisons showing that the physical activity amount decreased significantly across the three time periods (p < 0.05). The psychological distress of the participants did not appear to change during the regulation period. Although the participants' overall BSRS-5 score was slightly lower during the Level 2 alert period compared to the Level 3 alert period, the difference was not statistically significant (p = 0.264, Cohen's d = 0.08) based on a paired t-test. However, the levels of anxiety (p = 0.003, Cohen's d = 0.23) and inferiority (p = 0.034, Cohen's d = 0.159) were considerably higher during the Level 2 alert period than during the Level 3 alert period.

Conclusions

Our findings indicate that Taiwan’s COVID-19 alert levels influenced the physical activity behaviors and psychological distress of community-dwelling older adults. Time is required for older adults to regain their prior status after their physical activity behaviors and psychological distress were affected by national regulations.
The dose-response association between LEAP 1000 and birthweight – no clear mechanisms: a structural equation modeling approach
Authors: Quinones Sarah , Lin Shao , Tian Lili , Mendola Pauline , Novignon Jacob , Adamba Clement , Palermo Tia
Published: May 2023

Background

Birthweight is an important indicator of maternal and fetal health globally. The multifactorial origins of birthweight suggest holistic programs that target biological and social risk factors have great potential to improve birthweight. In this study, we examine the dose-response association of exposure to an unconditional cash transfer program before delivery with birthweight and explore the potential mediators of the association.

Methods

Data for this study come from the Livelihood Empowerment Against Poverty (LEAP) 1000 impact evaluation conducted between 2015 and 2017 among a panel sample of 2,331 pregnant and lactating women living in rural households of Northern Ghana. The LEAP 1000 program provided bi-monthly cash transfers and premium fee waivers to enroll in the National Health Insurance Scheme (NHIS). We used adjusted and unadjusted linear and logistic regression models to estimate the associations of months of LEAP 1000 exposure before delivery with birthweight and low birthweight, respectively. We used covariate-adjusted structural equation models (SEM) to examine mediation of the LEAP 1000 dose-response association with birthweight by household food insecurity and maternal-level (agency, NHIS enrollment, and antenatal care) factors.

Results

Our study included a sample of 1,439 infants with complete information on birthweight and date of birth. Nine percent of infants (N = 129) were exposed to LEAP 1000 before delivery. A 1-month increase in exposure to LEAP 1000 before delivery was associated with a 9-gram increase in birthweight and 7% reduced odds of low birthweight, on average, in adjusted models. We found no mediation effect by household food insecurity, NHIS enrollment, women’s agency, or antenatal care visits.

Conclusions

LEAP 1000 cash transfer exposure before delivery was positively associated with birthweight, though we did not find any mediation by household- or maternal-level factors. The results of our mediation analyses may serve to inform program operations and improve targeting and programming to optimize health and well-being among this population.

Trial Registration

The evaluation is registered in the International Initiative for Impact Evaluation’s (3ie) Registry for International Development Impact Evaluations (RIDIESTUDY- ID-55942496d53af) and in the Pan African Clinical Trial Registry (PACTR202110669615387).
Should we separately measure the pain parameter of the Constant-Murley score in patients with chronic shoulder pain?
Authors: Pires Rodrigues Gil Augusto , Vuistiner Philippe , Burrus Cyrille , Konzelmann Michel , Léger Bertrand , Luthi François
Published: May 2023

Background

The Constant-Murley Score (CMS) is a relatively unique shoulder assessment tool because it combines patient-reported outcomes (pain and activity), performance measurement and clinician-reported outcomes (strength and mobility). With these characteristics, the effect of patient-related psychological factors on the CMS remains debated. We aimed to investigate which parameters of the CMS are influenced by psychological factors by assessing the CMS before and after rehabilitation for chronic shoulder pain.

Methods

This retrospective study screened all patients (18–65 years old) who were admitted for interdisciplinary rehabilitation for chronic shoulder pain (≥ 3 months) between May 2012 and December 2017. Patients with unilateral shoulder injuries were eligible. Exclusion criteria were shoulder instability, concomitant neurological injuries, complex regional pain syndrome (including Steinbrocker syndrome), heavy psychiatric issues, and missing data. The Hospital Anxiety and Depression Scale, Pain Catastrophizing scale, and Tampa Scale of Kinesiophobia were administered before and after treatment. Regression models were used to estimate associations between psychological factors and the CMS.

Results

We included 433 patients (88% male, mean age 47±11 years) with a median duration of symptoms of 392.2 days (interquartile range: 266.5-583.5). Rotator cuff issue was present in 71% of patients. During interdisciplinary rehabilitation, patients were followed for a mean of 33.6±7.5 days. The mean CMS at entry was 42.8 ±15.5. The mean gain in CMS after treatment was 10.6 ±10.9. Before treatment, psychological factors were significantly associated with only the pain CMS parameter: -0.37 (95% CI: -0.46 to -0.28), p <0.001. After treatment, psychological factors were associated with the evolution of the four CMS parameters: -0.12 (-0.23 to -0.01) to -0.26 (95% CI: -0.36 to -0.16), p<0.05.

Conclusions

This study raises the question of a distinct assessment of pain when assessing shoulder function with CMS in patients with chronic shoulder pain. The separation of the “pain parameter” from the overall CMS score seems illusory with this tool that is used worldwide. However, clinicians should be aware that psychological factors can negatively influence the evolution of all CMS parameters during follow-up, which argues for a biopsychosocial approach to patients with chronic shoulder pain.
The experience of nurses to reduce implicit rationing of nursing care: a phenomenological study
Authors: Li Hui Qin , Xie Peng , Huang Xia , Luo Shan Xia
Published: May 2023

Background

Implicit rationing of nursing care can adversely affect patient safety and the quality of care, and increase nurses’ burnout and turnover tendency. Implicit rationing care occurs at the nurse-to-patient level (micro-level), and nurses are direct participants. Therefore, the strategies based on experience of nurses to reduce implicit rationing care have more reference value and promotion significance. The aim of the study is to explore the experience of nurses to reduce implicit rationing care, thereby to provide references for conducting randomized controlled trials to reduce implicit rationing care.

Methods

This is a descriptive phenomenological study. Purpose sampling was conducted nationwide. There are 17 nurses were selected and semi-structured in-depth interviews were conducted. The interviews were recorded, transcribed verbatim and analyzed via thematic analysis.

Results

Our study found that nurses’ reported experience of coping with implicit rationing of nursing care contained three aspects: personal, resource, and managerial. Three themes were extracted from the results of the study: (1) improving personal literacy; (2) supplying and optimizing resources and (3) standardizing management mode. The improvement of nurses’ own qualities are the prerequisites, the supply and optimization of resources is an effective strategy, and clear scope of work has attracted the attention of nurses.

Conclusion

The experience of dealing with implicit nursing rationing includes many aspects. Nursing managers should be grounded in nurses’ perspectives when developing strategies to reduce implicit rationing of nursing care. Promoting the improvement of nurses’ skills, improving staffing level and optimizing scheduling mode are promising measures to reduce hidden nursing rationing.
Patient expectations and levels of satisfaction in chiropractic treatment for lumbar radiculopathy. A mixed methods study
Authors: Jensen Rikke Krüger , Lillesø Sille , Jensen Jack Starche , Stochkendahl Mette Jensen
Published: May 2023

Background

Chiropractic patients are generally satisfied with the care received. It is unclear if this also applies to Danish patients with lumbar radiculopathy included in a standardised chiropractic care package (SCCP). This study aimed to investigate patient satisfaction and explore perspectives on the SCCP for lumbar radiculopathy.

Methods

An explanatory sequential mixed methods design with three separate phases was used. Phase one was a quantitative analysis based on a survey in a prospective cohort of patients with lumbar radiculopathy in an SCCP from 2018 to 2020. Patients rated their satisfaction with the examination, information, treatment effect, and overall management of their problem on a 0–10 scale. In phase two, six semi-structured interviews conducted in 2021 were used to gain further explanatory insights into the findings from phase one. Data were analysed using systematic text condensation. In phase three, the quantitative and qualitative data were merged in a narrative joint display to obtain a deeper understanding of the overall results.

Results

Of 303 eligible patients, 238 responded to the survey. Of these, 80–90% were very satisfied (≥ 8) when asked about the examination, information, and overall management, whereas 50% were very satisfied with the treatment effect. The qualitative analysis led to the emergence of four themes: ‘Understanding the standardised care packages’, ‘Expectations regarding consultation and treatment effect’, ‘Information about diagnosis and prognosis’, and ‘Interdisciplinary collaboration’. The joint display analysis showed that high patient satisfaction with the examination could be explained by the patients’ feeling of being carefully and thoroughly examined by the chiropractor and by referrals to MRI. Advice and information given to patients on variations in symptoms and the expected prognosis were considered reassuring. Satisfaction with the chiropractor’s coordination of care and with referral to other healthcare professionals was explained by the patients’ positive experiences of coordinated care and their sense of alleviated responsibility.

Conclusion

Overall, patients were satisfied with the SCCP for lumbar radiculopathy. From a patient’s perspective, the consultation should include a thorough examination and a focus on communication and information relating to symptoms and prognosis, while expectations regarding the content and efficacy of the treatment should be addressed and aligned.
Fixation-induced surgical segment’s high stiffness and the damage of posterior structures together trigger a higher risk of adjacent segment disease in patients with lumbar interbody fusion operations
Authors: Cai Ping , Xi Zhieng , Deng Chao , Li Jingchi , Zhang Xiaoyu , Zhou Yingguang
Published: May 2023

Background

Adjacent segment disease (ASD) is a commonly reported complication after lumbar interbody fusion (LIF); changes in the mechanical environment play an essential role in the generation of ASD. Traditionally, fixation-induced high stiffness in the surgical segment was the main reason for ASD. However, with more attention paid to the biomechanical significance of posterior bony and soft structures, surgeons hypothesize that this factor may also play an important role in ASD.

Methods

Oblique and posterior LIF operations have been simulated in this study. The stand-alone OLIF and OLIF fixed by bilateral pedicle screw (BPS) system have been simulated. The spinal process (the attachment point of cranial ligamentum complex) was excised in the PLIF model; the BPS system has also been used in the PLIF model. Stress values related to ASD have been computed under physiological body positions, including flexion, extension, bending, and axial rotations.

Results

Compared to the stand-alone OLIF model, the OLIF model with BPS fixation suffers higher stress values under extension body position. However, there are no apparent differences under other loading conditions. Moreover, significant increases in stress values can be recorded in flexion and extension loading conditions in the PLIF model with posterior structures damage.

Conclusions

Fixation-induced surgical segment’s high stiffness and the damage of posterior soft tissues together trigger a higher risk of ASD in patients with LIF operations. Optimizing BPS fixation methods and pedicle screw designs and reducing the range of posterior structures excision may be an effective method to reduce the risk of ASD.
Combined inhibition of histone deacetylase and cytidine deaminase improves epigenetic potency of decitabine in colorectal adenocarcinomas
Authors: Tang Zijiao , Liu Lu , Borlak Jürgen
Published: May 2023

Background

Targeting the epigenome of cancerous diseases represents an innovative approach, and the DNA methylation inhibitor decitabine is recommended for the treatment of hematological malignancies. Although epigenetic alterations are also common to solid tumors, the therapeutic efficacy of decitabine in colorectal adenocarcinomas (COAD) is unfavorable. Current research focuses on an identification of combination therapies either with chemotherapeutics or checkpoint inhibitors in modulating the tumor microenvironment. Here we report a series of molecular investigations to evaluate potency of decitabine, the histone deacetylase inhibitor PBA and the cytidine deaminase (CDA) inhibitor tetrahydrouridine (THU) in patient derived functional and p53 null colon cancer cell lines (CCCL). We focused on the inhibition of cell proliferation, the recovery of tumor suppressors and programmed cell death, and established clinical relevance by evaluating drug responsive genes among 270 COAD patients. Furthermore, we evaluated treatment responses based on CpG island density.

Results

Decitabine caused marked repression of the DNMT1 protein. Conversely, PBA treatment of CCCL recovered acetylation of histone 3 lysine residues, and this enabled an open chromatin state. Unlike single decitabine treatment, the combined decitabine/PBA treatment caused > 95% inhibition of cell proliferation, prevented cell cycle progression especially in the S and G2-phase and induced programmed cell death. Decitabine and PBA differed in their ability to facilitate re-expression of genes localized on different chromosomes, and the combined decitabine/PBA treatment was most effective in the re-expression of 40 tumor suppressors and 13 genes typically silenced in cancer-associated genomic regions of COAD patients. Furthermore, this treatment repressed expression of 11 survival (anti-apoptotic) genes and augmented expression of X-chromosome inactivated genes, especially the lncRNA Xist to facilitate p53-mediated apoptosis. Pharmacological inhibition of CDA by THU or its gene knockdown prevented decitabine inactivation. Strikingly, PBA treatment recovered the expression of the decitabine drug-uptake transporter SLC15A1, thus enabling high tumor drug-loads. Finally, for 26 drug responsive genes we demonstrated improved survival in COAD patients.

Conclusion

The combined decitabine/PBA/THU drug treatment improved drug potency considerably, and given their existing regulatory approval, our findings merit prospective clinical trials for the triple combination in COAD patients.
Sex differences in the effects of high fat diet on underlying neuropathology in a mouse model of VCID
Authors: Abi-Ghanem Charly , Salinero Abigail E. , Kordit David , Mansour Febronia M. , Kelly Richard D. , Venkataganesh Harini , Kyaw Nyi-Rein , Gannon Olivia J. , Riccio David , Fredman Gabrielle , Poitelon Yannick , Belin Sophie , Kopec Ashley M. , Robison Lisa S. , Zuloaga Kristen L.
Published: May 2023

Background

Damage to the cerebral vasculature can lead to vascular contributions to cognitive impairment and dementia (VCID). A reduction in blood flow to the brain leads to neuropathology, including neuroinflammation and white matter lesions that are a hallmark of VCID. Mid-life metabolic disease (obesity, prediabetes, or diabetes) is a risk factor for VCID which may be sex-dependent (female bias).

Methods

We compared the effects of mid-life metabolic disease between males and females in a chronic cerebral hypoperfusion mouse model of VCID. C57BL/6J mice were fed a control or high fat (HF) diet starting at ~ 8.5 months of age. Three months after diet initiation, sham or unilateral carotid artery occlusion surgery (VCID model) was performed. Three months later, mice underwent behavior testing and brains were collected to assess pathology.

Results

We have previously shown that in this VCID model, HF diet causes greater metabolic impairment and a wider array of cognitive deficits in females compared to males. Here, we report on sex differences in the underlying neuropathology, specifically white matter changes and neuroinflammation in several areas of the brain. White matter was negatively impacted by VCID in males and HF diet in females, with greater metabolic impairment correlating with less myelin markers in females only. High fat diet led to an increase in microglia activation in males but not in females. Further, HF diet led to a decrease in proinflammatory cytokines and pro-resolving mediator mRNA expression in females but not males.

Conclusions

The current study adds to our understanding of sex differences in underlying neuropathology of VCID in the presence of a common risk factor (obesity/prediabetes). This information is crucial for the development of effective, sex-specific therapeutic interventions for VCID.
Rapid restitution of contractile dysfunction by synthetic copolymers in dystrophin-deficient single live skeletal muscle fibers
Authors: Hahn Dongwoo , Quick Joseph D. , Thompson Brian R. , Crabtree Adelyn , Hackel Benjamin J. , Bates Frank S. , Metzger Joseph M.
Published: May 2023

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, a cytoskeletal protein essential for the preservation of the structural integrity of the muscle cell membrane. DMD patients develop severe skeletal muscle weakness, degeneration, and early death. We tested here amphiphilic synthetic membrane stabilizers in mdx skeletal muscle fibers (flexor digitorum brevis; FDB) to determine their effectiveness in restoring contractile function in dystrophin-deficient live skeletal muscle fibers. After isolating FDB fibers via enzymatic digestion and trituration from thirty-three adult male mice (9 C57BL10, 24 mdx), these were plated on a laminin-coated coverslip and treated with poloxamer 188 (P188; PEO75-PPO30-PEO75; 8400 g/mol), architecturally inverted triblock (PPO15-PEO200-PPO15, 10,700 g/mol), and diblock (PEO75-PPO16-C4, 4200 g/mol) copolymers. We assessed the twitch kinetics of sarcomere length (SL) and intracellular Ca2+ transient by Fura-2AM by field stimulation (25 V, 0.2 Hz, 25 °C). Twitch contraction peak SL shortening of mdx FDB fibers was markedly depressed to 30% of the dystrophin-replete control FDB fibers from C57BL10 (P < 0.001). Compared to vehicle-treated mdx FDB fibers, copolymer treatment robustly and rapidly restored the twitch peak SL shortening (all P < 0.05) by P188 (15 μM =  + 110%, 150 μM =  + 220%), diblock (15 μM =  + 50%, 150 μM =  + 50%), and inverted triblock copolymer (15 μM =  + 180%, 150 μM =  + 90%). Twitch peak Ca2+ transient from mdx FDB fibers was also depressed compared to C57BL10 FDB fibers (P < 0.001). P188 and inverted triblock copolymer treatment of mdx FDB fibers increased the twitch peak Ca2+ transient (P < 0.001). This study shows synthetic block copolymers with varied architectures can rapidly and highly effectively enhance contractile function in live dystrophin-deficient skeletal muscle fibers.
Surgical site infection surveillance in German hospitals: a national survey to determine the status quo of digitalization
Authors: Aghdassi Seven Johannes Sam , Goodarzi Hengameh , Gropmann Alexander , Clausmeyer Jörg , Geffers Christine , Piening Brar , Gastmeier Petra , Behnke Michael
Published: May 2023

Background

Surveillance of surgical site infections (SSI) relies on access to data from various sources. Insights into the practices of German hospitals conducting SSI surveillance and their information technology (IT) infrastructures are scarce. The aim of this study was to evaluate current SSI surveillance practices in German hospitals with a focus on employed IT infrastructures.

Methods

German surgical departments actively participating in the national SSI surveillance module “OP-KISS” were invited in August 2020 to participate in a questionnaire-based online survey. Depending on whether departments entered all data manually or used an existing feature to import denominator data into the national surveillance database, departments were separated into different groups. Selected survey questions differed between groups.

Results

Of 1,346 invited departments, 821 participated in the survey (response rate: 61%). Local IT deficits (n = 236), incompatibility of import specifications and hospital information system (n = 153) and lack of technical expertise (n = 145) were cited as the most frequent reasons for not using the denominator data import feature. Conversely, reduction of workload (n = 160) was named as the main motivation to import data. Questions on data availability and accessibility in the electronic hospital information system (HIS) and options to export data from the HIS for the purpose of surveillance, yielded diverse results. Departments utilizing the import feature tended to be from larger hospitals with a higher level of care.

Conclusions

The degree to which digital solutions were employed for SSI surveillance differed considerably between surgical departments in Germany. Improving availability and accessibility of information in HIS and meeting interoperability standards will be prerequisites for increasing the amount of data exported directly from HIS to national databases and laying the foundation for automated SSI surveillance on a broad scale.
Transcriptome profiling uncovers the involvement of CmXyn1, a glycosyl hydrolase 11, in Cochliobolus miyabeanus pathogenicity
Authors: Lee Gi Hyun , Yoo Ju Soon , Oh Ha-Ram , Min Cheol Woo , Jang Jeong Woo , Mukherjee Soumya , Jung Ki-Hong , Kim Yu-Jin , Wang Yiming , Gupta Ravi , Kim Sun Tae
Published: May 2023

Necrotrophic pathogen Cochliobolus miyabeanus (C. miyabeanus) causes rice brown leaf spot disease and drastically affects the yield and quality of rice grains. However, the molecular mechanism of rice-C. miyabeanus remains poorly understood due to the limited research conducted on this pathosystem. To elucidate the molecular mechanism of rice-C. miyabeanus, a transcriptome analysis was conducted from in vitro and in planta grown C. miyabeanus. This analysis led to the identification of a total of 24,060 genes of which 426 in vitro and 57 in planta expressed genes were predicted to encode for secretory proteins. As these 57 genes were specifically expressed in planta and were predicted to be secretory in nature, these were consider as putative effectors, highlighting their possible roles in the fungal pathogenicity. Notably, among these putative effectors, CmXyn1 which encodes a glycosyl hydrolase 11 displayed the highest expression level under in planta conditions and was thus selected for further functional characterization. Interestingly, the extracellular expression of CmXyn1 transiently induced cell death in Nicotiana benthamiana leaves, while intracellular expression was comparatively lesser effective. In addition, transcriptome analysis on rice leaves during C. miyabeanus infection and comparing it to the rice leaf transcriptome data obtained during hemibiotrophic pathogen Magnaporthe oryzae infection led to the discovery of 18 receptors/receptor-like kinases that were commonly expressed in response to both pathogens, indicating their key roles in rice defense response. Taken together, our findings provide new insights into rice-C. miyabeanus interaction as well as the unique and common defense responses of rice against hemibiotroph and necrotroph model systems.
Rule-based process indicators of information processing explain performance differences in PIAAC web search tasks
Authors: Hahnel Carolin , Kroehne Ulf , Goldhammer Frank
Published: May 2023

Background

A priori assumptions about specific behavior in test items can be used to process log data in a rule-based fashion to identify the behavior of interest. In this study, we demonstrate such a top-down approach and created a process indicator to represent what type of information processing (flimsy, breadth-first, satisficing, sampling, laborious) adults exhibit when searching online for information. We examined how often the predefined patterns occurred for a particular task, how consistently they occurred within individuals, and whether they explained task success beyond individual background variables (age, educational attainment, gender) and information processing skills (reading and evaluation skills).

Methods

We analyzed the result and log file data of ten countries that participated in the Programme for the International Assessment of Adult Competencies (PIAAC). The information processing behaviors were derived for two items that simulated a web search environment. Their explanatory value for task success was investigated with generalized linear mixed models.

Results

The results showed item-specific differences in how frequently specific information processing patterns occurred, with a tendency of individuals not to settle on a single behavior across items. The patterns explained task success beyond reading and evaluation skills, with differences across items as to which patterns were most effective for solving a task correctly. The patterns even partially explained age-related differences.

Conclusions

Rule-based process indicators have their strengths and weaknesses. Although dependent on the clarity and precision of a predefined rule, they allow for a targeted examination of behaviors of interest and can potentially support educational intervention during a test session. Concerning adults’ digital competencies, our study suggests that the effective use of online information is not inherently based on demographic factors but mediated by central skills of lifelong learning and information processing strategies.
Demography and disorders of English Cocker Spaniels under primary veterinary care in the UK
Authors: Engdahl Karolina S. , Brodbelt Dave C. , Cameron Carla , Church David B. , Hedhammar Åke , O’Neill Dan G.
Published: May 2023

Background

The English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS.

Results

English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25–8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12–17.35). The annual proportional birth rate was relatively stable between 2.97–3.51% from 2005–2016. The most common specific diagnoses were periodontal disease (n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31–22.62), otitis externa (n = 234, 10.09%, 95% CI: 8.87–11.32), obesity (n = 229, 9.88%, 95% CI: 8.66–11.09), anal sac impaction (n = 187, 8.07%, 95% CI: 6.96–9.18), diarrhoea (n = 113, 4.87%, 95% CI: 4.00–5.75), and aggression (n = 93, 4.01%, 95% CI: 3.21–4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) (P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) (P = 0.010). The median age at death was 11.44 years (IQR 9.46–13.47) and the most common grouped causes of death were neoplasia (n = 10, 9.26%, 95% CI: 3.79–14.73), mass-associated disorders (n = 9, 8.33%, 95% CI: 4.45–15.08), and collapse (n = 8, 7.41%, 95% CI: 3.80–13.94).

Conclusions

Periodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS.
Development of cardiac risk prediction model in patients with HER-2 positive breast cancer on trastuzumab therapy
Authors: Otchere Prince , Adekoya Olusola , Governor Samuel B. , Vuppuluri Naveen , Prabhakar Akruti , Pak Stella , Oppong-Nkrumah Oduro , Cook Francis , Bohinc Rudy , Aune Gregory
Published: May 2023

Background

25% of all breast cancer patients have HER-2 overexpression. Breast Cancer patients with HER-2 overexpression are typically treated with HER-2 inhibitors such as Trastuzumab. Trastuzumab is known to cause a decrease in left ventricular ejection fraction. The aim of this study is to create a cardiac risk prediction tool among women with Her-2 positive breast cancer to predict cardiotoxicity.

Method

Using a split sample design, we created a risk prediction tool using patient level data from electronic medical records. The study included women 18 years of age and older diagnosed with HER-2 positive breast cancer who received Trastuzumab. Outcome measure was defined as a drop in LVEF by more than 10% to less than 53% at any time in the 1-year study period. Logistic regression was used to test predictors.

Results

The cumulative incidence of cardiac dysfunction in our study was 9.4%. The sensitivity and specificity of the model are 46% and 84%, respectively. Given a cumulative incidence of cardiotoxicity of 9%, the negative predictive value of the test was 94%. This suggests that in a low-risk population, the interval of screening for cardiotoxicity may be performed less frequently.

Conclusion

Cardiac risk prediction tool can be used to identify Her-2 positive breast cancer patients at risk of developing cardiac dysfunction. Also, test characteristics in addition to disease prevalence may inform a rational strategy in performing cardiac ultrasound in Her-2 breast cancer patients. We have developed a cardiac risk prediction model with high NPV in a low-risk population which has an appealing cost-effectiveness profile.