bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the association between perceived stigma, its correlates, and restrictions in participation among persons with disabilities in Nepal: a cross-sectional study
Authors: Devkota Hridaya Raj , Poudel Sasmita , Shrestha Mohan Krishna , Oli Radhika Upreti , Rai Nabin Kumar , Poudel Manish , Banjara Pradeep , Malla Catherine , Hazel Yadira Perez , Dahal Anjila , Gurung Reeta
Published: April 2024

Background

Disability stigma in low- and middle-income countries is one of the most persistent and complex barriers limiting persons with disabilities (PwDs) from enjoying their rights and opportunities. Perceived stigma among PwDs and its impact on participation restriction is rarely assessed in Nepal.

Objective

This study aimed to measure the extent of perceived stigma by PwDs, identify its relationships with specific demographic factors, and assess the impact on social participation.

Methods

A cross-sectional survey was conducted between May and July 2022 among PwDs in Nepal, with a sample of 371. The Explanatory Model Interview Catalog (EMIC) stigma scale and P-scale suitable for people affected by stigmatized conditions were used, and the generated scores were analyzed. One-way ANOVA was performed to determine group differences for sociodemographic variables, and linear regression and correlational analysis were used to identify their association and measure the strength and direction of the relationship.

Results

The mean stigma score was 16.9 (SD 13.8). 42% of respondents scored higher than the mean. The scores differed significantly by disability type, caste and ethnicity, education, occupation, and household wealth. Over 56% reported participation restriction, and 38% had severe/extreme restriction. Approximately 65% of participants with intellectual disabilities, 53% with multiple disabilities, and 48.5% of persons with severe or profound disabilities experienced severe or extreme restrictions. Perceived stigma had a positive correlation with Disability type (r = 0.17, P < 0.01) and negative correlations with Severity of disability (r= -0.15, P < 0.05), and Household wealth (r= -0.15, P < 0.01). Education was inversely associated with both stigma (r= -0.24, P < 0.01), and participation restriction (β= -9.34, P < 0.01). However, there was no association between stigma and participation restriction (β= -0.10, P > 0.05).

Conclusion

All participants exhibited stigma in general; however, the severity varied based on disability type, level of education, and sociocultural circumstances. A large proportion of participants reported facing a high degree of restrictions in participation; however, no association was detected between perceived stigma and participation restriction. A significant negative linear correlation was observed between education and participation restriction. Stigma reduction programs focusing on education and empowerment would be especially important for overcoming internalized stigma and increasing the participation of PwDs.
Comparison of the efficacy of the convex side short fusion combined with concave side single growing rod technique and the traditional bilateral growing rod technique in the treatment of early onset scoliosis
Authors: Zhu Weiwei , Zhang Xuejun , Cao Jun , Zhang Baihui , Chen Wenhao , Bai Yunsong , Guo Dong , Yao Ziming
Published: April 2024

Objectives

The application of a growing rod technique can retain the growth and development potential of the spine and thorax while controlling the progression of scoliosis deformity. Theoretically, convex side short fusion combined with a concave side single growing rod technique can significantly reduce the asymmetric growth of the spine in the vertex region in most patients. However, the final clinical outcome of various techniques is yet to be clearly determined and compared between studies. Therefore, we compared the efficacy of these two growing rod techniques in treating early onset scoliosis.

Methods

In a retrospective study of 152 EOS patients seen between 2013.1 and 2019.12, 36 cases of EOS patients were selected for inclusion. Among the 36 cases, 11 cases were treated with convex side short fusion combined with a concave side single growing rod technique, group (A) The remaining 25 cases were treated with traditional bilateral growing rod technique, group (B) Age, gender, etiology, follow-up time, Cobb angle of main curve, T1-S1 height, coronal trunk shift, sagittal vertical axis (SVA), Cobb angle of thoracic kyphosis at last follow-up, and Cobb angle at proximal junction kyphosis of the first and last post-operation follow-up were recorded. In addition, internal fixation related complications, infection, nervous system complications were recorded as well.

Results

There was no statistically significant difference between group A and group B in preoperative age, Cobb angle of main curve, coronal trunk shift, T1-S1 height, SVA, Cobb angle of thoracic kyphosis (p > 0.05). However, at the last follow-up (Group A, mean 4.4 ± 1.01 years; Group B, mean 3.6 ± 0.01 years) the Cobb angle of the main curve was less and T1-S1 height greater in group A compared with group B (p < 0.05). There was no statistically significant difference between group A and group B in the correction rate of the Cobb angle of the main curve or the growth rate of T1-S1 height (p > 0.05). There was no statistically significant difference in the coronal imbalance ratio, thoracic kyphosis abnormality ratio, or the occurrence PJK ratio between group A and group B at the last follow-up (p > 0.05), but the sagittal imbalance ratio and internal fixation abnormality ratio were higher in group A than in the group B (p < 0.05).

Conclusions

During the treatment of EOS, both the convex side short fusion combined with concave side single growing rod technique and traditional bilateral growing rod technique can correct the Cobb angle of main curve with no significant hindering of the spinal growth observed. The traditional bilateral growing rod technique has advantages in control of the sagittal balance of the spine, and the complications associated with internal fixation were lower.
LC-MS/MS profiling of Tipuana tipu flower, HPLC-DAD quantification of its bioactive components, and interrelationships with antioxidant, and anti-inflammatory activity: in vitro and in silico approaches
Authors: Ibrahim Rana M. , Abdel-Baki Passent M. , El-Rashedy Ahmed A. , Mahdy Nariman E.
Published: April 2024

Background

Fabaceae plays a crucial role in African traditional medicine as a source of large number of important folk medication, agriculture and food plants. In a search of potential antioxidant and anti-inflammatory candidates derived from locally cultivated plants, the flowers of Tipuana tipu (Benth.) Lillo growing in Egypt were subjected to extensive biological and phytochemical studies. The impact of the extraction technique on the estimated biological activities was investigated.

Methods

The flowers were extracted using different solvents (aqueous, methanol, water/methanol (1:1), methanol/methylene chloride (1:1), and methylene chloride). The different extracts were subjected to antioxidant (DPPH, ABTS, and FRAP) and anti-inflammatory (COX-2 and 5-LOX) assays. The methanol extract was assessed for its inhibitory activity against iNOS, NO production, and pro-inflammatory cytokines (NF-KB, TNF-R2, TNF-α, IL-1β, and IL-6) in LPS-activated RAW 264.7 macrophages. The composition-activity relationship of the active methanol extract was further investigated using a comprehensive LC–QTOF-MS/MS analysis. The major identified phenolic compounds were further quantified using HPLC-DAD technique. The affinity of representative compounds to iNOS, COX-2, and 5-LOX target active sites was investigated using molecular docking and molecular dynamics simulations.

Results

The methanol extract exhibited the highest radical scavenging capacity and enzyme inhibitory activities against COX-2 and 5-LOX enzymes with IC50 values of 10.6 ± 0.4 and 14.4 ± 1.0 µg/mL, respectively. It also inhibited iNOS enzyme activity, suppressed NO production, and decreased the secretion of pro-inflammatory cytokines. In total, 62 compounds were identified in the extract including flavonoids, coumarins, organic, phenolic, and fatty acids. Among them 18 phenolic compounds were quantified by HPLC-DAD. The highest docking scores were achieved by kaempferol-3-glucoside and orientin. Additionally, molecular dynamics simulations supported the docking findings.

Conclusion

The flower could be considered a potentially valuable component in herbal medicines owing to its unique composition and promising bioactivities. These findings encourage increased propagation of T. tipu or even tissue culturing of its flowers for bioprospecting of novel anti-inflammatory drugs. Such applications could be adopted as future approaches that benefit the biomedical field.
Relationship between learning styles and clinical competency in nursing students
Authors: Mousavi Seyed Kazem , Javadzadeh Ali , Hasankhani Hanieh , Parizad Zahra Alijani
Published: April 2024

Background

The acquisition of clinical competence is considered the ultimate goal of nursing education programs. This study explored the relationship between learning styles and clinical competency in undergraduate nursing students.

Methods

A descriptive-correlational study was conducted in 2023 with 276 nursing students from the second to sixth semesters at Abhar School of Nursing, Zanjan University of Medical Sciences, Iran. Data were collected using demographic questionnaires, Kolb’s learning styles, and Meretoja’s clinical competence assessments completed online by participants. Data were analyzed using SPSS version 16, employing descriptive statistics and inferential tests (independent T-test, ANOVA, Pearson correlation) at a significance level 0.05.

Results

The predominant learning styles among nursing students were divergent (31.2%), and the least common was convergent (18.4%). The overall clinical competency score was 77.25 ± 12.65. Also, there was a significant relationship between learning styles and clinical competency, so the clinical competency of students with accommodative and converging learning styles was higher. (P < 0.05).

Conclusion

The results of this study showed the association between learning styles and clinical competence in nursing students. It is recommended that educational programs identify talented students and provide workshops tailored to strengthen various learning styles associated with enhanced clinical competence.
Psychosocial characteristics pattern correlated with suicidal ideation and non-suicidal self-injury among nurse staff: a latent profile analysis
Authors: Li Xuehua , Ding Changmian , Li Guizhi , Duan Zhizhou
Published: April 2024

Background

Nurses frequently endure elevated levels of psychosocial stress, which often correlates with an increased suicide risk. This study aimed to investigate the impact of latent psychosocial characteristic patterns on suicidal ideation and non-suicidal self-injury among nursing staff.

Method

Participants were recruited from the Dehong districts of Yunnan province, China, between July 11th and July 26th, 2022. Subgroups were identified using variables linked to suicidal ideation and non-suicidal self-injury, including perceived cognitive deficits, anxiety symptoms, depressive symptoms, resilience, social support, childhood trauma, loneliness, and sleep quality. Measurement tools included the Perceived Deficit Questionnaire-5-item (PDQ-5), Generalized Anxiety Disorder-7 items (GAD-7), Patient Health Questionnaire (PHQ-9), Connor-Davidson Resilience Scale-10 items (CD-RISC10), Multidimensional Scale of Perceived Social Support (MSPSS), Childhood Trauma Questionnaire-Short Form (CTQ-SF), Three-Item Loneliness Scale, and a single-item sleep quality scale.

Results

Latent profile analysis (LPA) revealed four distinct psychosocial characteristic patterns: “class 1,” “class 2,” “class 3,” and “class 4.” Compared to class 2, individuals in class 1 had a sixfold increased risk of suicidal ideation (OR = 6.59, 95%CI = 4.42–9.81) and a fivefold increased risk of non-suicidal self-injury (OR = 5.13, 95%CI = 3.38–7.78). Similarly, class 4 individuals had twice the risk of suicidal ideation (OR = 2.13, 95%CI = 1.25–3.62) and non-suicidal self-injury (OR = 2.13, 95%CI = 1.25–3.65) compared to class 2. Conversely, class 3 individuals had a lower risk of suicidal ideation (OR = 0.21, 95%CI = 0.11–0.42) and non-suicidal self-injury (OR = 0.15, 95%CI = 0.07–0.36) than class 2. Additionally, divorced/other marital status individuals had a higher risk of suicidal ideation (OR = 2.34, 95%CI = 1.02–5.35) and non-suicidal self-injury (OR = 2.58, 95%CI = 1.01–6.65) compared to married individuals, while unmarried individuals had a lower risk of suicidal ideation (OR = 0.58, 95%CI = 0.37–0.91).

Conclusions

The study identified eight important psychosocial factors divided into four latent pattern classes. Individuals in “class 1” and “class 4” were more likely to have a higher risk of suicidal ideation and non-suicidal self-injury, while those in “class 3” were more likely to have a lower risk of both outcomes. It is suggested that further research should focus on “class 1” and “class 4” for targeted intervention.
Needs assessment in long-term care: expression of national principles for priority setting in service allocation
Authors: Pedersen Ann Katrin Blø , Skinner Marianne Sundlisæter , Sogstad Maren
Published: April 2024

Background

Long-term care services for older adults are characterised by increasing needs and scarce resources. Political strategies have led to the reorganisation of long-term care services, with an increased focus on “ageing in place” and efficient use of resources. There is currently limited research on the processes by which resource allocation decisions are made by service allocators of long-term care services for older adults. The aim of this study is to explore how three political principles for priority setting in long-term care, resource, severity and benefit, are expressed in service allocation to older adults.

Methods

This qualitative study uses data from semi-structured individual interviews, focus groups and observations of service allocators who assess needs and assign long-term care services to older adults in Norway. The data were supplemented with individual decision letters from the allocation office, granting or denying long-term care services. The data were analysed using reflexive thematic analysis.

Results

The allocators drew on all three principles for priority setting when assessing older adults’ long-term care needs and allocating services. We found that the three principles pushed in different directions in the allocation process. We identified six themes related to service allocators’ expression of the principles: (1) lowest effective level of care as a criterion for service allocation (resource), (2) blanket allocation of low-cost care services (resource), (3) severity of medical and rehabilitation needs (severity), (4) severity of care needs (severity), (5) benefit of generous service allocation (benefit) and (6) benefit of avoiding services (benefit).

Conclusions

The expressions of the three political principles for priority setting in long-term care allocation are in accordance with broader political trends and discourses regarding “ageing in place”, active ageing, an investment ideology, and prioritising those who are “worse off”. Increasing attention to the rehabilitation potential of older adults and expectations that they will take care of themselves increase the risk of not meeting frail older adults’ care needs. Additionally, difficulties in defining the severity of older adults’ complex needs lead to debates regarding “worse off” versus potentiality in future long-term care services allocation.

Trial registration

Not applicable.
Asking about violence and abuse among patients experiencing homelessness: a focus group study with healthcare professionals
Authors: Gaber Sophie Nadia , Rydeman Ing-Britt , Mattsson Elisabet , Kneck Åsa
Published: April 2024

Background

People experiencing homelessness are at increased risk of violence and abuse, however, there is insufficient knowledge about rates of inquiry or readiness of healthcare professionals to address violence and abuse among this population. This study aimed to explore healthcare professionals’ experiences and perceptions of asking about violence and abuse among patients experiencing homelessness.

Methods

This study used a qualitative, interpretive, and exploratory design. We performed focus group discussions with healthcare professionals (n = 22) working at an integrative healthcare unit for people experiencing homelessness. Data were analysed using reflexive thematic analysis, following Braun and Clarke’s six-phase approach. Findings are reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist.

Results

The overarching theme of the analysis is that addressing violence and abuse is at risk of “falling through the cracks”. The theme is supported by three sub-themes: Hesitance to address violence and abuse, The complex dynamics of violence and abuse in homelessness, and Challenges in addressing violence and abuse amidst competing priorities and collaborative efforts. The normalisation of violence and abuse within the context of homelessness perpetuates a “cycle” where the severity and urgency of addressing violence and abuse are overlooked or minimised, hindering effective interventions. Moreover, healthcare professionals themselves may inadvertently contribute to this normalisation. The hesitance expressed by healthcare professionals in addressing the issue further reinforces the prevailing belief that violence and abuse are inherent aspects of homelessness. This normalisation within the healthcare system adds another layer of complexity to addressing these issues effectively.

Conclusions

The findings underscore the need for targeted interventions and coordinated efforts that not only address the immediate physical needs of people experiencing homelessness but also challenge and reshape the normalised perceptions surrounding violence and abuse. By prioritising awareness, education, and supportive interventions, we can begin to “break the cycle” and provide a safer environment where violence and abuse are not accepted or overlooked.
A novel COL4A5 splicing mutation causes alport syndrome in a Chinese family
Authors: Chen Suyun , Xu Guangbiao , Zhao Zhixin , Du Juping , Shen Bo , Li Chunping
Published: April 2024

Background

Alport syndrome (AS) is characterised by haematuria, proteinuria, a gradual decline in kidney function, hearing loss, and eye abnormalities. The disease is caused by mutations in COL4An (n = 3, 4, 5) that encodes 3–5 chains of type IV collagen in the glomerular basement membrane. AS has three genetic models: X-linked, autosomal recessive, and autosomal dominant. The most common type of AS is X-linked AS, which is caused by COL4A5.

Methods

We enrolled children with renal insufficiency and a family history of kidney disorders. The proband was identified using whole-exome sequencing. Sanger sequencing was performed to verify the mutation site. Minigene technology was used to analyse the influence of mutant genes on pre-mRNA shearing, and the Iterative Threading ASSEmbly Refinement (I-TASSER) server was used to analyse the protein structure changes.

Results

The proband, together with her mother and younger brother, displayed microscopic haematuria and proteinuria, Pathological examination revealed mesangial hyperplasia and sclerosis. A novel mutation (NM_000495.5 c.4298-8G > A) in the intron of the COL4A5 gene in the proband was discovered, which was also present in the proband’s mother, brother, and grandmother. In vitro minigene expression experiments verified that the c.4298-8G > A mutation caused abnormal splicing, leading to the retention of six base pairs at the end of intron 46. The I-TASSER software predicted that the mutation affected the hydrogen-bonding structure of COL4A5 and the electrostatic potential on the surface of the protein molecules.

Conclusions

Based on the patient’s clinical history and genetic traits, we conclude that the mutation at the splicing site c.4298-8G > A of the COL4A5 gene is highly probable to be the underlying cause within this particular family. This discovery expands the genetic spectrum and deepens our understanding of the molecular mechanisms underlying AS.
Syndromic ciliopathy: a taiwanese single-center study
Authors: Pan Yu-Wen , Ou Tsung-Ying , Chou Yen-Yin , Kuo Pao-Lin , Hsiao Hui-Pin , Chiu Pao-Chin , Lin Ju-Li , Lo Fu-Sung , Wang Chung-Hsing , Chen Peng-Chieh , Tsai Meng-Che
Published: April 2024

Background

Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes.

Methods

The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment.

Results

A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation.

Conclusions

Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.
Short reads-based characterization of pathotype diversity and drug resistance among Escherichia coli isolated from patients attending regional referral hospitals in Tanzania
Authors: Kanje Livin E. , Kumburu Happiness , Kuchaka Davis , Shayo Mariana , Juma Masoud A. , Kimu Patrick , Beti Melkiory , van Zwetselaar Marco , Wadugu Boaz , Mmbaga Blandina T. , Mkumbaye Sixbert Isdory , Sonda Tolbert
Published: April 2024

Background

Escherichia coli is known to cause about 2 million deaths annually of which diarrhea infection is leading and typically occurs in children under 5 years old. Although Africa is the most affected region there is little information on their pathotypes diversity and their antimicrobial resistance.

Objective

To determine the pathotype diversity and antimicrobial resistance among E. coli from patients attending regional referral hospitals in Tanzania.

Materials and methods

A retrospective cross-section laboratory-based study where a total of 138 archived E. coli isolates collected from 2020 to 2021 from selected regional referral hospitals in Tanzania were sequenced using the Illumina Nextseq550 sequencer platform. Analysis of the sequences was done in the CGE tool for the identification of resistance genes and virulence genes. SPSS version 20 was used to summarize data using frequency and proportion.

Results

Among all 138 sequenced E. coli isolates, the most prevalent observed pathotype virulence genes were of extraintestinal E. coli UPEC fyuA gene 82.6% (114/138) and NMEC irp gene 81.9% (113/138). Most of the E. coli pathotypes observed exist as a hybrid due to gene overlapping, the most prevalent pathotypes observed were NMEC/UPEC hybrid 29.7% (41/138), NMEC/UPEC/EAEC hybrid 26.1% (36/138), NMEC/UPEC/DAEC hybrid 18.1% (25/138) and EAEC 15.2% (21/138). Overall most E. coli carried resistance gene to ampicillin 90.6% (125/138), trimethoprim 85.5% (118/138), tetracycline 79.9% (110/138), ciprofloxacin 76.1% (105/138) and 72.5% (100/138) Nalidixic acid. Hybrid pathotypes were more resistant than non-hybrid pathotypes.

Conclusion

Whole genome sequencing reveals the presence of hybrid pathotypes with increased drug resistance among E. coli isolated from regional referral hospitals in Tanzania.
DEC1 is involved in circadian rhythm disruption-exacerbated pulmonary fibrosis
Authors: Chen Shuai-Jun , Yu Fan , Feng Xiao , Li Qian , Jiang Ye-Han , Zhao Li-Qin , Cheng Pei-Pei , Wang Meng , Song Lin-Jie , Liang Li-Mei , He Xin-Liang , Xiong Liang , Xiang Fei , Wang Xiaorong , Ye Hong , Ma Wan-Li
Published: April 2024

Background

The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear.

Results

In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-β1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis.

Conclusions

Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.
The clinical relevance of different antiphospholipid antibody profiles in pediatric rheumatology patients
Authors: Pandya Jheel , Onel Karen , Erkan Doruk
Published: April 2024

Background

The clinical relevance of different antiphospholipid antibody (aPL) profiles, including low level anticardiolipin (aCL) and anti-β2-glycoprotein-I (aβ2GPI) antibodies, is ill-defined in the pediatric population. Our purpose is to describe the demographic, clinical, and laboratory characteristics of aPL positive pediatric patients based on different aPL profiles.

Findings

In this single center retrospective cohort study, based on the screening of our pediatric (age ≤ 18) rheumatology electronic medical records (2016–2022), we identified patients who had at least one “positive” aPL (lupus anticoagulant [LA], aCL IgG/M, or aβ2GPI IgG/M) result. Patients were grouped into high- (LA positive and/or aCL/aβ2GPI IgG/M > 40U [ELISA]) and low-risk (LA negative and aCL/aβ2GPI IgG/M 20-39U) aPL profiles; those with persistently positive aPL were descriptively analyzed for demographic and clinical characteristics. Of 57 included patients, 34 (59%) had initial high- and 23 (40%) had initial low-risk profiles. Based on subsequent aPL results available in 42/57 (74%) patients, 25/27 (93%) in the high-, and 7/15 (47%) in the low-risk groups remained still positive. Of these 32 patients with persistently positive aPL, moderate-to-large vessel or microvascular thrombosis occurred in nine (28%) patients with high-risk and in none with low-risk aPL profiles; non-thrombotic aPL-related manifestations were reported in 15 (47%) patients with persistent aPL positivity.

Conclusion

An initial high-risk aPL profile was persistent in approximately 90% of our cohort, a third of whom had thrombosis, and half had non-thrombotic aPL manifestations. Our results underscore the need for a large-scale effort to better characterize aPL-related manifestations in pediatric patients with persistent high-risk aPL-profiles.
Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction
Authors: Wu Zhipeng , Geng Nan , Liu Zhao , Pan Wen , Zhu Yueke , Shan Jing , Shi Hongbo , Han Ying , Ma Yingmin , Liu Bo
Published: April 2024

Background

There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking.

Methods

A total of 226 COVID-19 patients admitted to Beijing Youan Hospital’s emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed.

Results

A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737–0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis.

Conclusion

Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.
Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review
Authors: Ma Tiancheng , Wang Yan , Ma Jianxiong , Cui Hongwei , Feng Xiaotian , Ma Xinlong
Published: April 2024

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the “angiogenesis and osteogenesis coupling”, and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the “angiogenesis-osteogenesis coupling” and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.
Carbon sequestration costs and spatial spillover effects in China's collective forests
Authors: Zhou Yifan , Xue Caixia , Liu Shuohua , Zhang Jinrong
Published: April 2024

Background

Global climate change is one of the major challenges facing the world today, and forests play a crucial role as significant carbon sinks and providers of ecosystem services in mitigating climate change and protecting the environment. China, as one of the largest developing countries globally, owns 60% of its forest resources collectively. Evaluating the carbon sequestration cost of collective forests not only helps assess the contribution of China’s forest resources to global climate change mitigation but also provides important evidence for formulating relevant policies and measures.

Results

Over the past 30 years, the carbon sequestration cost of collective forests in China has shown an overall upward trend. Except for coastal provinces, southern collective forest areas, as well as some southwestern and northeastern regions, have the advantage of lower carbon sequestration costs. Furthermore, LSTM network predictions indicate that the carbon sequestration cost of collective forests in China will continue to rise. By 2030, the average carbon sequestration cost of collective forests is projected to reach 125 CNY per ton(= 16.06 Euros/t). Additionally, there is spatial correlation in the carbon sequestration cost of collective forests. Timber production, labor costs, and labor prices have negative spatial spillover effects on carbon sequestration costs, while land opportunity costs, forest accumulation, and rural resident consumption have positive spatial spillover effects.

Conclusion

The results of this study indicate regional disparities in the spatial distribution of carbon sequestration costs of collective forests, with an undeniable upward trend in future cost growth. It is essential to focus on areas with lower carbon sequestration costs and formulate targeted carbon sink economic policies and management measures to maximize the carbon sequestration potential of collective forests and promote the sustainable development of forestry.
Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease
Authors: Mahboobipour Amir Ali , Ala Moein , Safdari Lord Javad , Yaghoobi Arash
Published: April 2024

Polycystic liver disease (PLD) is a rare condition observed in three genetic diseases, including autosomal dominant polycystic liver disease (ADPLD), autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). PLD usually does not impair liver function, and advanced PLD becomes symptomatic when the enlarged liver compresses adjacent organs or increases intra-abdominal pressure. Currently, the diagnosis of PLD is mainly based on imaging, and genetic testing is not required except for complex cases. Besides, genetic testing may help predict patients’ prognosis, classify patients for genetic intervention, and conduct early treatment. Although the underlying genetic causes and mechanisms are not fully understood, previous studies refer to primary ciliopathy or impaired ciliogenesis as the main culprit. Primarily, PLD occurs due to defective ciliogenesis and ineffective endoplasmic reticulum quality control. Specifically, loss of function mutations of genes that are directly involved in ciliogenesis, such as Pkd1, Pkd2, Pkhd1, and Dzip1l, can lead to both hepatic and renal cystogenesis in ADPKD and ARPKD. In addition, loss of function mutations of genes that are involved in endoplasmic reticulum quality control and protein folding, trafficking, and maturation, such as PRKCSH, Sec63, ALG8, ALG9, GANAB, and SEC61B, can impair the production and function of polycystin1 (PC1) and polycystin 2 (PC2) or facilitate their degradation and indirectly promote isolated hepatic cystogenesis or concurrent hepatic and renal cystogenesis. Recently, it was shown that mutations of LRP5, which impairs canonical Wnt signaling, can lead to hepatic cystogenesis. PLD is currently treated by somatostatin analogs, percutaneous intervention, surgical fenestration, resection, and liver transplantation. In addition, based on the underlying molecular mechanisms and signaling pathways, several investigational treatments have been used in preclinical studies, some of which have shown promising results. This review discusses the clinical manifestation, complications, prevalence, genetic basis, and treatment of PLD and explains the investigational methods of treatment and future research direction, which can be beneficial for researchers and clinicians interested in PLD.
SF3B3-regulated mTOR alternative splicing promotes colorectal cancer progression and metastasis
Authors: Xu Tong , Li Xichuan , Zhao Wennan , Wang Xue , Jin Leixin , Feng Zhiqiang , Li Huixiang , Zhang Mingzhe , Tian Yiqing , Hu Ge , Yue Yuan , Dai Xintong , Shan Changliang , Zhang Weihua , Zhang Chunze , Zhang Youcai
Published: April 2024

Background

Aberrant alternative splicing (AS) is a pervasive event during colorectal cancer (CRC) development. SF3B3 is a splicing factor component of U2 small nuclear ribonucleoproteins which are crucial for early stages of spliceosome assembly. The role of SF3B3 in CRC remains unknown.

Methods

SF3B3 expression in human CRCs was analyzed using publicly available CRC datasets, immunohistochemistry, qRT-PCR, and western blot. RNA-seq, RNA immunoprecipitation, and lipidomics were performed in SF3B3 knockdown or overexpressing CRC cell lines. CRC cell xenografts, patient-derived xenografts, patient-derived organoids, and orthotopic metastasis mouse models were utilized to determine the in vivo role of SF3B3 in CRC progression and metastasis.

Results

SF3B3 was upregulated in CRC samples and associated with poor survival. Inhibition of SF3B3 by RNA silencing suppressed the proliferation and metastasis of CRC cells in vitro and in vivo, characterized by mitochondria injury, increased reactive oxygen species (ROS), and apoptosis. Mechanistically, silencing of SF3B3 increased mTOR exon-skipped splicing, leading to the suppression of lipogenesis via mTOR-SREBF1-FASN signaling. The combination of SF3B3 shRNAs and mTOR inhibitors showed synergistic antitumor activity in patient-derived CRC organoids and xenografts. Importantly, we identified SF3B3 as a critical regulator of mTOR splicing and autophagy in multiple cancers.

Conclusions

Our findings revealed that SF3B3 promoted CRC progression and metastasis by regulating mTOR alternative splicing and SREBF1-FASN-mediated lipogenesis, providing strong evidence to support SF3B3 as a druggable target for CRC therapy.
The skåne emergency medicine (SEM) cohort
Authors: Ekelund Ulf , Ohlsson Bodil , Melander Olle , Björk Jonas , Ohlsson Mattias , Forberg Jakob Lundager , de Capretz Pontus Olsson , Nyström Axel , Björkelund Anders
Published: April 2024

Background

In the European Union alone, more than 100 million people present to the emergency department (ED) each year, and this has increased steadily year-on-year by 2–3%. Better patient management decisions have the potential to reduce ED crowding, the number of diagnostic tests, the use of inpatient beds, and healthcare costs.

Methods

We have established the Skåne Emergency Medicine (SEM) cohort for developing clinical decision support systems (CDSS) based on artificial intelligence or machine learning as well as traditional statistical methods. The SEM cohort consists of 325 539 unselected unique patients with 630 275 visits from January 1st, 2017 to December 31st, 2018 at eight EDs in the region Skåne in southern Sweden. Data on sociodemographics, previous diseases and current medication are available for each ED patient visit, as well as their chief complaint, test results, disposition and the outcome in the form of subsequent diagnoses, treatments, healthcare costs and mortality within a follow-up period of at least 30 days, and up to 3 years.

Discussion

The SEM cohort provides a platform for CDSS research, and we welcome collaboration. In addition, SEM’s large amount of real-world patient data with almost complete short-term follow-up will allow research in epidemiology, patient management, diagnostics, prognostics, ED crowding, resource allocation, and social medicine.
Polygenic scores for longitudinal prediction of incident type 2 diabetes in an ancestrally and medically diverse primary care physician network: a patient cohort study
Authors: Mandla Ravi , Schroeder Philip , Porneala Bianca , Florez Jose C. , Meigs James B. , Mercader Josep M. , Leong Aaron
Published: April 2024

Background

The clinical utility of genetic information for type 2 diabetes (T2D) prediction with polygenic scores (PGS) in ancestrally diverse, real-world US healthcare systems is unclear, especially for those at low clinical phenotypic risk for T2D.

Methods

We tested the association of PGS with T2D incidence in patients followed within a primary care practice network over 16 years in four hypothetical scenarios that varied by clinical data availability (N = 14,712): (1) age and sex; (2) age, sex, body mass index (BMI), systolic blood pressure, and family history of T2D; (3) all variables in (2) and random glucose; and (4) all variables in (3), HDL, total cholesterol, and triglycerides, combined in a clinical risk score (CRS). To determine whether genetic effects differed by baseline clinical risk, we tested for interaction with the CRS.

Results

PGS was associated with incident T2D in all models. Adjusting for age and sex only, the Hazard Ratio (HR) per PGS standard deviation (SD) was 1.76 (95% CI 1.68, 1.84) and the HR of top 5% of PGS vs interquartile range (IQR) was 2.80 (2.39, 3.28). Adjusting for the CRS, the HR per SD was 1.48 (1.40, 1.57) and HR of the top 5% of PGS vs IQR was 2.09 (1.72, 2.55). Genetic effects differed by baseline clinical risk ((PGS-CRS interaction p = 0.05; CRS below the median: HR 1.60 (1.43, 1.79); CRS above the median: HR 1.45 (1.35, 1.55)).

Conclusions

Genetic information can help identify high-risk patients even among those perceived to be low risk in a clinical evaluation.
Successful preimplantation genetic testing for fibrodysplasia ossificans progressiva: a case report
Authors: Murugesu Sughashini , Jones Benjamin P. , Serhal Paul , Ben-Nagi Jara
Published: April 2024

Purpose of the study

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant condition that leads to significant disability and morbidity, characterised by the formation of heterotopic hard tissues within connective tissues. The condition has an incidence of approximately one per two million people worldwide. There is no known single effective treatment available for FOP. We report the world’s first case of a healthy infant born following in vitro fertilisation (IVF) and preimplantation genetic testing for monogenic disorder (PGT-M) using Karyomapping for FOP.

Case presentation

A 30-year-old Caucasian female with FOP presented with her partner seeking IVF with PGT-M to achieve a healthy pregnancy with an embryo unaffected by FOP.

Methods

The couple underwent IVF and PGT-M using Karyomapping as the testing method. A multi-disciplinary team approach was utilised in planning this case, considering the additional risks of oocyte retrieval, pregnancy and childbirth in women with FOP.

Main findings

The oocyte retrieval was covered with a 5-day course of prednisolone to reduce the risk of a localised inflammatory reaction, which could result in subsequent heterotopic ossification. This was subsequently weaned down with reducing doses every two days. The patient underwent uncomplicated oocyte retrieval, yielding 12 mature oocytes. Following intracytoplasmic sperm injection (ICSI), ten zygotes having two pro-nuclei were cultured, and six underwent trophoectoderm biopsy and vitrification 5–6 days after retrieval. PGT-M via Karyomapping revealed four out of six (66.7%) of blastocysts were not carriers of the maternal high-risk FOP allele. In total, the patient had three separate embryo transfers. Pregnancy was achieved following the third frozen embryo transfer, which went to 37 weeks’ gestation, and delivered by Caesarean section. The baby was born in excellent condition and is unaffected by FOP.

Conclusion

IVF/ICSI and PGT-M using Karyomapping was successfully implemented to identify embryos carrying the high-risk FOP allele resulting in a healthy livebirth.
Classification of battery compounds using structure-free Mendeleev encodings
Authors: Zhuang Zixin , Barnard Amanda S.
Published: April 2024

Machine learning is a valuable tool that can accelerate the discovery and design of materials occupying combinatorial chemical spaces. However, the prerequisite need for vast amounts of training data can be prohibitive when significant resources are needed to characterize or simulate candidate structures. Recent results have shown that structure-free encoding of complex materials, based entirely on chemical compositions, can overcome this impediment and perform well in unsupervised learning tasks. In this study, we extend this exploration to supervised classification, and show how structure-free encoding can accurately predict classes of material compounds for battery applications without time consuming measurement of bonding networks, lattices or densities.

Scientific contribution

The comprehensive evaluation of structure-free encodings of complex materials in classification tasks, including binary and multi-class separation, inclusive of three classifiers based on different logic function, is measured four metrics and learning curves. The encoding is applied to two data sets from computational and experimental sources, and the outcomes visualised using 5 approaches to confirms the suitability and superiority of Mendeleev encoding. These methods are general and accessible using source software, to provide simple, intuitive and interpretable materials informatics outcomes to accelerate materials design.