bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of resilience training on stress, hope and psychological toughness of mothers living with mentally and physically disabled children
Authors: Sharifian Pegah , kuchaki Zeinab , shoghi Mahnaz
Published: May 2024

Introduction

Welfare and rehabilitation centers prioritize the welfare of children over the mental and physical well-being of mothers. The present study aimed to determine the impact of resilience training on stress, hope, and psychological toughness of mothers living with mentally and physically disabled children.

Materials and methods

This intervention study was conducted in the Hamadan (Iran) Welfare and Rehabilitation Center in 2023. To this end, 70 parents of children with mental and physical disabilities were randomly selected and then randomly assigned to two control and intervention groups. In the intervention group, 9 resilience training sessions were conducted, each lasting 60 min. These meetings were held weekly at the welfare and rehabilitation center. The resilience training included three components: (1) exploring the concept of resilience within families and the attributes of individuals with high resilience, (2) examining internal and external factors that influence resilience, and (3) studying the strategies for enhancing family resilience. No intervention was performed in the control group. Data collection was done using parental stress, hope, and psychological toughness questionnaire. The mothers of both groups completed the above questionnaires both before and one month after the intervention. Data analysis was performed using chi-square (χ2), Kruskal-Wallis, and t-test with SPSS software (version 23) at a significance level of 0.05.

Results

Before the intervention, there was no statistically significant difference in parental stress between the two groups (p = 0.370). However, after the intervention, the difference between the two groups became statistically significant (p = 0.001). Similarly, there was no significant difference in parents’ hope before the intervention (p = 0.452), but a significant difference was observed after the intervention (p = 0.001). Besides, parental psychological toughness was not significant before the intervention (p = 0.179) but became significant after the intervention (p = 0.000).

Conclusion

Based on the results, resilience training reduced parental stress and increased hope and resilience in mothers of the test group. Therefore, resilience training is recommended to lower parental stress and increase the hope and psychological toughness of mothers of mentally and physically disabled children.
‘We did everything by phone’: a qualitative study of mothers' experience of smartphone-aided screening of cerebral palsy in Kathmandu, Nepal
Authors: Kukka Antti J. , Bhattarai Pratiksha , Sundelin Heléne E. K. , Gurung Rejina , Brown Nick J. W. , Litorp Helena , Axelin Anna , KC Ashish
Published: May 2024

Background

International guidelines recommend early intervention to all children at risk of cerebral palsy, but targeted screening programs are often lacking in low- and middle-income settings with the highest burden of disease. Smartphone applications have the potential to improve access to early diagnostics by empowering parents to film their children at home followed by centralized evaluation of videos with General Movements Assessment. We explored mothers’ perceptions about participating in a smartphone aided cerebral palsy screening program in Kathmandu, Nepal.

Methods

This is an explorative qualitative study that used focus group discussions (n = 2) and individual interviews (n = 4) with mothers of term-born infants surviving birth asphyxia or neonatal seizures. Parents used the NeuroMotion™ smartphone app to film their children at home and the videos were analysed using Precthl’s General Movements Assessment. Sekhon et al.’s framework on the acceptability of health care interventions guided the design of the group discussions and interviews, and the deductive qualitative content analysis.

Results

Mothers were interested in engaging with the programme and expressed hope it would benefit their children. Most felt using the app was intuitive. They were, however, unclear about the way the analysis was performed. Support from the research team was often needed to overcome an initial lack of self-confidence in using the technology, and to reduce anxiety related to the follow-up. The intervention was overall perceived as recommendable but should be supplemented by a face-to-face consultation.

Conclusion

Smartphone aided remote screening of cerebral palsy is acceptable in a lower middle-income population but requires additional technical support.
Patterns and short term neurosurgical treatment outcomes of neonates with neural tube defects admitted to Felege Hiwot Specialized Hospital, Bahir Dar, Ethiopia
Authors: Addisu Yohannes , Wassie Gizachew Tadesse
Published: May 2024

Background

Neural tube defects (NTDs) account for the largest proportion of congenital anomalies of the central nervous system and result from failure of the neural tube to close spontaneously between the 3rd and 4th weeks of in utero development. Prognosis and treatment outcome depends on the nature and the pattern of the defect. The nature of treatment outcomes and its pattern associated with grave prognosis is not well known in the study area.

Objective

The aim of study was to determine the patterns and short term neurosurgical management outcomes of newborns with neural tube defects admitted at Felege Hiwot Specialized Hospital.

Methods

Institutional based retrospective cross-sectional study among neonates, who were admitted at Felege Hiwot Specialized Hospital with neural tube defects from January 1st to December, 30th, 2018 was conducted. All Charts of Neonates with confirmed diagnosis of neural tube defects were included as part of the study. Trained data collectors (medical interns) supervised by trained supervisors (general practitioners) collected the data using a pretested data extraction format. Data were coded, entered and analyzed using SPSS version 23 software. Frequency and cross tabulations were used to summarize descriptive statistics of data, and tables and graphs were used for data presentation.

Result

About 109 patients had complete documentation and imaging confirmed neural tube defects. Myelomeningocele was the commonest pattern 70 (64.2%). Thoracolumbar spine was the commonest site of presentation 49(45%). The most common associated impairment was hydrocephalus 37(33.9%). Forty-five (41.1%) had multiple complications. The mortality rate was 7.3%, 44% were discharged with sequalae and 36.7% were discharged without impairment. The significant causes of death were infection 66.7% and Chiari crisis 33.3%.

Conclusion

Myelomeningocele was the most frequent clinical pattern of neural tube defect and thoracolumbar spine was the commonest site. Isolated neural tube defect was the commonest finding. There were multiple complications after surgery accompanied with meningitis and hydrocephalus. The mortality rate among neonates with neural tube defects was considerably high. The commonest causes of death were infection and Chiari crisis.
Risk of not being in employment, education or training (NEET) in late adolescence is signalled by school readiness measures at 4–5 years
Authors: Warburton Matthew , Wood Megan L. , Sohal Kuldeep , Wright John , Mon-Williams Mark , Atkinson Amy L.
Published: May 2024

Background

Not being in employment, education, or training (NEET) is associated with poor health (physical and mental) and social exclusion. We investigated whether England’s statutory school readiness measure conducted at 4–5 years provides a risk signal for NEET in late adolescence.

Methods

We identified 8,118 individuals with school readiness measures at 4–5 years and NEET records at 16–17 years using Connected Bradford, a bank of linked routinely collected datasets. Children were categorised as ‘school ready’ if they reached a ‘Good Level of Development’ on the Early Years Foundation Stage Profile. We used probit regression and structural equation modelling to investigate the relationship between school readiness and NEET status and whether it primarily relates to academic attainment.

Results

School readiness was significantly associated with NEET status. A larger proportion of young people who were not school ready were later NEET (11%) compared to those who were school ready (4%). Most of this effect was attributable to shared relationships with academic attainment, but there was also a direct effect. Measures of deprivation and Special Educational Needs were also strong predictors of NEET status.

Conclusions

NEET risk factors occur early in life. School readiness measures could be used as early indicators of risk, with interventions targeted to prevent the long-term physical and mental health problems associated with NEET, especially in disadvantaged areas. Primary schools are therefore well placed to be public health partners in early intervention strategies.
Patterns of care at the end of life: a retrospective study of Italian patients with advanced breast cancer
Authors: Giannubilo Irene , Battistuzzi Linda , Blondeaux Eva , Ruelle Tommaso , Poggio Francesca Benedetta , Buzzatti Giulia , D’Alonzo Alessia , Della Rovere Federica , Latocca Maria Maddalena , Molinelli Chiara , Razeti Maria Grazia , Nardin Simone , Arecco Luca , Perachino Marta , Favero Diletta , Borea Roberto , Pronzato Paolo , Del Mastro Lucia , Bighin Claudia
Published: May 2024

Objectives

To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death.

Methods

One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected.

Results

98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support.

Conclusions

Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy.
Investigating spiritual care perceptions and religious coping methods among the relatives of terminally ill patients during the COVID-19 pandemic: the case of Turkey
Authors: Cetın Zuhal , Ozen Betul
Published: May 2024

Background

The COVID-19 pandemic in Turkey and around the world has had a profound impact on the families of terminally ill patients. In this challenging period, investigating the spiritual care perceptions and religious coping methods of patients' relatives is an essential step towards understanding the experiences in this process with the additional challenges brought by the pandemic and developing appropriate support services. This study aims to determine the spiritual care perceptions and the use of religious coping methods among the relatives of terminally ill patients in Turkey during the COVID-19 pandemic.

Methods

The sample of this descriptive and correlational study consisted of the relatives of terminally ill patients (n = 147) who were receiving treatment in the Anesthesiology and Reanimation Intensive Care Unit of a state hospital in Turkey. Spirituality and Spiritual Care Rating Scale and the Religious Coping Scale to them using face-to-face interviews. Mann–Whitney U test, Kruskal–Wallis test, and Spearman's correlation analysis were used to analyze the data.

Results

The mean age of the participants was 38.84 ± 11.19 years. Also, 63.3% of them were employed. The participant's total score on the Spirituality and Spiritual Care Rating Scale was 57.16 ± 6.41, and it was determined that the participants' level of perception of spirituality and spiritual care concepts was close to good. When the Religious Coping Scale scores of the participants were examined, it was found that both Positive Religious Coping levels (23.11 ± 2.34) and Negative Religious Coping levels (9.48 ± 1.47) were close to high. There was no correlation between the scores of RCOPE and SSCRS (p > 0.05).

Conclusion

As a result, it was determined that the level of perception of spirituality and spiritual care concepts of the relatives of terminally ill patients during the COVID-19 pandemic was close to sound, and their Positive Religious Coping levels were high. Epidemics are a reality of the world, and it is essential to learn lessons from this process and take precautions for the future. We offer a perspective to realize the coping power of religion and spirituality, which are integral parts of life. The needs of terminally ill patients' relatives, a sensitive group, become visible.
Effects of Satureja Khuzestanica supplementation on glycemic indices and lipid profile in type 2 diabetes patients: a randomized controlled clinical-trial
Authors: Roosta Sajjad , Ghasemi Fatemeh , Mokhayeri Yaser , Choobkar Saeed , Nikbakht Mohammad Reza , Falahi Ebrahim
Published: May 2024

Background

Several studies showed the hypoglycemic and hypolipidemic effects of Satureja Khuzestanica (SK) in animal models. This study aimed to determine the effect of SK supplementation on glycemic and lipid outcomes of patients with type 2 diabetes mellitus (T2DM).

Methods

The study was designed as a double-blind, placebo-controlled, randomized clinical trial using block randomization. Seventy-eight T2DM patients were randomly assigned to intervention (n = 39) or placebo (n = 39) groups. They received SK or placebo in 500 mg capsules daily for 12 weeks. Anthropometric, blood pressure, liver enzymes, glycemic, and lipid outcomes were measured before and after the intervention.

Results

At baseline, there were no significant differences in age, sex, or glycated hemoglobin (HbA1c) levels between the groups. SK supplementation led to a significant decrease in FBS (-12.6 ± 20.7 mg/dl in the intervention group versus 3.5 ± 31.9 mg/dl; p = 0.007), HbA1c (-0.28 ± 0.45 in the intervention group versus 0.11 ± 0.54% in the placebo group; p = < 0.001), insulin (-1.65 ± 6.18 in the intervention group versus 2.09 ± 5.90 mIU/L in the placebo group; p = 0.03), total cholesterol (-14.6 ± 21.1 mg/dl in the intervention group versus 8.2 ± 30.9 mg/dl in the placebo group; p < 0.001), LDL-cholesterol (-4.6 ± 15.2 mg/dl in the intervention group versus 5.8 ± 14.6 mg/dl in placebo group; p < 0.001) levels, and significant increase in HDL-cholesterol (3.9 ± 4.9 mg/dl in the intervention group versus 0.9 ± 5.2 mg/dl in placebo group; p = 0.005).

Conclusion

Based on the study results, SK supplementation may improve glycemic indices and lipid profile of patients with T2DM. Our findings may provide novel complementary treatments without adverse effects for diabetes complications. These results need to be further confirmed in clinical trials.

Registration

: This trial has been registered in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20190715044214N1, registration date: 21/02/2021).
Standing together at the helm – how employees experience employee-driven innovation in primary care
Authors: Samuelson Sarah , Pennbrant Sandra , Svensson Ann , Svenningsson Irene
Published: May 2024

Primary care needs to find strategies to deal with today’s societal challenges and continue to deliver efficient and high-quality care. Employee-driven innovation is increasingly gaining ground as an accessible pathway to developing successful and sustainable organisations. This type of innovation is characterised by employees being engaged in the innovation process, based on a bottom-up approach. This qualitative study explores employees’ experiences of employee-driven innovation at a primary care centre in Sweden. Data are collected by focus group interviews and analysed by inductive qualitative content analysis. The result is presented with the overarching theme “Standing together at the helm” followed by three categories: “Motivating factors for practising employee-driven innovation”, “Challenges in practising employee-driven innovation” and “Benefits of employee-driven innovation”, including nine subcategories. The study found that employee-driven innovation fosters organisational innovation, empowers employees, and enhances adaptability at personal and organisational levels. This enables individual and collective learning, and facilitates the shaping, development, and adaptation of working methods to meet internal and external requirements. However, new employees encountered difficulty grasping the concept of employee-driven innovation and recognising its long-term advantages. Additionally, the demanding and task-focused environment within primary care posed challenges in sustaining efforts in innovation work. The employees also experienced a lack of external support to drive and implement some innovative ideas.
Recombinant multiepitope proteins expressed in Escherichia coli cells and their potential for immunodiagnosis
Authors: Gonçalves Ana Alice Maia , Ribeiro Anna Julia , Resende Carlos Ananias Aparecido , Couto Carolina Alves Petit , Gandra Isadora Braga , dos Santos Barcelos Isabelle Caroline , da Silva Jonatas Oliveira , Machado Juliana Martins , Silva Kamila Alves , Silva Líria Souza , dos Santos Michelli , da Silva Lopes Lucas , de Faria Mariana Teixeira , Pereira Sabrina Paula , Xavier Sandra Rodrigues , Aragão Matheus Motta , Candida-Puma Mayron Antonio , de Oliveira Izadora Cristina Moreira , Souza Amanda Araujo , Nogueira Lais Moreira , da Paz Mariana Campos , Coelho Eduardo Antônio Ferraz , Giunchetti Rodolfo Cordeiro , de Freitas Sonia Maria , Chávez-Fumagalli Miguel Angel , Nagem Ronaldo Alves Pinto , Galdino Alexsandro Sobreira
Published: May 2024

Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes’ high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using theEscherichia coliexpression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits.
Mild therapeutic hypothermia upregulates the O-GlcNAcylation level of COX10 to alleviate mitochondrial damage induced by myocardial ischemia–reperfusion injury
Authors: Deng Wei , Chen Yixuan , Zhang Jing , Ling Jitao , Xu Zhou , Zhu Zicheng , Tang Xiaoyi , Liu Xiao , Zhang Deju , Zhu Hong , Lang Haili , Zhang Lieliang , Hua Fuzhou , Yu Shuchun , Qian Kejian , Yu Peng
Published: May 2024

Objective

Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia–reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia–reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia–reperfusion injury and the O-GlcNAcylation level of COX10.

Methods

We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia–reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence.

Results

Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia–reperfusion injury. In vivo, MTH effectively alleviates ischemia–reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects.

Conclusions

In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia–reperfusion injury, which provides important theoretical basis for the clinical application of MTH.
Assessing the impact of early progressive mobilization on moderate-to-severe traumatic brain injury: a randomized controlled trial
Authors: Yen Hsiao-Ching , Chuang Hung-Jui , Hsiao Wei-Ling , Tsai Yun-Chen , Hsu Po-Min , Chen Wen-Shiang , Han Yin-Yi
Published: May 2024

Introduction

Traumatic brain injury (TBI) is a major cause of neurodisability worldwide, with notably high disability rates among moderately severe TBI cases. Extensive previous research emphasizes the critical need for early initiation of rehabilitation interventions for these cases. However, the optimal timing and methodology of early mobilization in TBI remain to be conclusively determined. Therefore, we explored the impact of early progressive mobilization (EPM) protocols on the functional outcomes of ICU-admitted patients with moderate to severe TBI.

Methods

This randomized controlled trial was conducted at a trauma ICU of a medical center; 65 patients were randomly assigned to either the EPM group or the early progressive upright positioning (EPUP) group. The EPM group received early out-of-bed mobilization therapy within seven days after injury, while the EPUP group underwent early in-bed upright position rehabilitation. The primary outcome was the Perme ICU Mobility Score and secondary outcomes included Functional Independence Measure motor domain (FIM-motor) score, phase angle (PhA), skeletal muscle index (SMI), the length of stay in the intensive care unit (ICU), and duration of ventilation.

Results

Among 65 randomized patients, 33 were assigned to EPM and 32 to EPUP group. The EPM group significantly outperformed the EPUP group in the Perme ICU Mobility and FIM-motor scores, with a notably shorter ICU stay by 5.9 days (p < 0.001) and ventilation duration by 6.7 days (p = 0.001). However, no significant differences were observed in PhAs.

Conclusion

The early progressive out-of-bed mobilization protocol can enhance mobility and functional outcomes and shorten ICU stay and ventilation duration of patients with moderate-to-severe TBI. Our study’s results support further investigation of EPM through larger, randomized clinical trials.

Clinical trial registration ClinicalTrials.gov NCT04810273. Registered 13 March 2021.
Genetic prediction of the relationship between metabolic syndrome and colorectal cancer risk: a Mendelian randomization study
Authors: Yuan Chendong , Shu Xufeng , Hu Zhenzhen , Jie Zhigang
Published: May 2024

Background

Despite a growing body of observational studies indicating a potential link between metabolic syndrome and colorectal cancer, a definitive causal relationship has yet to be established. This study aimed to elucidate the causal relationship between metabolic syndrome and colorectal cancer through Mendelian randomization.

Methods

We screened for instrumental variables associated with metabolic syndrome and its diagnostic components and with colorectal cancer through the use of a genome-wide association study database, and conducted a preliminary Mendelian randomization analysis. To corroborate the dependability of our conclusions, an additional dataset was used for replication analysis in a Mendelian randomization method, which was further integrated with a meta-analysis.

Results

Preliminary analysis using the inverse variance weighted method revealed positive correlations between metabolic syndrome (OR [95% CI] = 1.37[1.15–1.63], P = 5.02 × 10–4) and waist circumference (OR [95% CI] = 1.39[1.21–1.61], P = 7.38 × 10–6) and the risk of colorectal cancer. Replication analysis also revealed the same results: metabolic syndrome (OR [95% CI] = 1.24[1.02–1.51], P = 0.030) and waist circumference (OR [95% CI] = 1.23[1.05–1.45], P = 0.013). The meta-analysis results further confirmed the associations between metabolic syndrome (OR [95% CI] = 1.31[1.15–1.49], P < 0.001) and waist circumference (OR [95% CI] = 1.32[1.18–1.47], P < 0.001) and colorectal cancer.

Conclusion

Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.
TBX3 transfection and nodal signal pathway inhibition promote differentiation of adipose mesenchymal stem cell to cardiac pacemaker-like cells
Authors: Basalamah Faris , Dilogo Ismail Hadisoebroto , Raharjo Sunu Budhi , Mansyur Muchtaruddin , Siregar Nuryati Chairani , Ibrahim Nurhadi , Setianto Budi Yuli , Yuniadi Yoga
Published: May 2024

Background

Mesenchymal stem cells (MSCs) are known as one of the best candidate cells to produce cardiac pacemaker-like cells (CPLCs). Upregulation of TBX3 transcription factor and inhibition of the nodal signal pathway have a significant role in the formation of cardiac pacemaker cells such as sinoatrial and atrioventricular nodes, which initiate the heartbeat and control the rhythm of heart contractions. This study aimed to confirm the effects of transfection of TBX3 transcription factor and inhibition of the nodal signal pathway on differentiating adipose-derived MSCs (AD-MSCs) to CPLCs. AD-MSCs were characterized using flow cytometry and three-lineage differentiation staining.

Methods

The transfection of TBX3 plasmid was carried out using lipofectamine, and inhibition of the nodal signal pathway was done using the small-molecule SB431542. The morphology of the cells was observed using a light microscope. Pacemaker-specific markers, including TBX3, Cx30, HCN4, HCN1, HCN3, and KCNN4, were evaluated using the qRT-PCR method. For protein level, TBX3 and Cx30 were evaluated using ELISA and immunofluorescence staining. The electrophysiology of cells was evaluated using a patch clamp.

Results

The TBX3 expression in the TBX3, SM, and TBX + SM groups significantly higher (p < 0.05) compared to the control group and cardiomyocytes. The expression of Cx40 and Cx43 genes were lower in TBX3, SM, TBX + SM groups. In contrast, Cx30 gene showed higher expression in TBX3 group. The expression HCN1, HCN3, and HCN4 genes are higher in TBX3 group.

Conclusion

The transfection of TBX3 and inhibition of the nodal signal pathway by small-molecule SB431542 enhanced differentiation of AD-MSCs to CPLCs.
Morphology, taxonomy and trophic interactions of rostrum-less coleoids from the Late Triassic Polzberg Konservat-Lagerstätte (Lower Austria)
Authors: Lukeneder Petra , Fuchs Dirk , Lukeneder Alexander
Published: May 2024

Coleoid cephalopods are widespread from the Mesozoic till today. The extinct group of the Phragmoteuthida is thought to represent either stem-neocoleoids, stem-decabrachians, or stem-octobrachians. The well-known, almost complete specimens of Phragmoteuthis bisinuata from the Carnian Polzberg Konservat-Lagerstätte near Lunz am See (Lower Austria, Northern Calcareous Alps) and Cave del Predil (Northern Italy, Julian Alps) come from historical collections. These specimens do not reflect the entire coleoid assemblage within this environment. In order to obtain a more complete picture of the Carnian coleoid fauna, 430 coleoid specimens from the Polzberg locality and 60 specimens from contemporaneous localities around Cave del Predil were studied in detail. All available elements (phragmocones, proostraca, cartilages, hooks, beaks, ink sacs) attributed to the coleoid fauna were recorded, measured and evaluated taxonomically and taphonomically. Reviews of historical collection material permitted comparisons with recently collected material. The notation of co-occurrences of other faunal elements yielded insights into the palaeoecological context of this Upper Triassic environment within the Polzberg Basin. The new material from Polzberg does not support the previous assumption of a monospecific composition of the Polzberg coleoid fauna. Instead, we report the occurrence of the new phragmoteuthid Phragmoteuthis polzbergensis nov. sp. and a newly excavated specimen of Phragmoteuthis indicates the presence of ten arms within the group of the Phragmoteuthida for the first time. Phragmocones with small opening angles combined with cylindrical (roundly closed) body chambers, and arm hook types which are unusual for phragmoteuthids indicate the presence of the basal coleoid group comprising the rostrum-less genus Mojsisovicsteuthis.

ZooBank LSID: urn:lsid:zoobank.org:pub:7EE7425C-6B0C-4800-925A-52D9108C13C7.
Pneumocystis pneumonia in French intensive care units in 2013–2019: mortality and immunocompromised conditions
Authors: Kamel Toufik , Boulain Thierry
Published: May 2024

Purpose

The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described.

Methods

We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019.

Results

French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without.

Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17–0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient’s age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients.

Conclusions

The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals.
Three-dimensional chromatin landscapes in MLLr AML
Authors: Sui Pinpin , Wang Zhihong , Zhang Peng , Pan Feng
Published: May 2024

Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.
Characteristic burn temperature markers of bones as revealed by electron paramagnetic resonance
Authors: Knaflič Tilen , Legan Lea , Cavalli Fabio , Ropret Polonca
Published: May 2024

This research paper presents a novel methodology for determining the burn temperature of archaeological bones using electron paramagnetic resonance (EPR) supported by Fourier Transform Infrared (FTIR) spectroscopy. A selection of bone samples, burned at different temperatures, were examined with EPR. The EPR spectra displayed dependency on burn temperature, showing characteristic narrow spectra of carbon radicals, Mn

$$^{2+}$$

2
+

signals and signals from different carbonate ions. This methodology was applied to selected archaeological samples of burnt bones, successfully determining the burn temperature these bones were exposed to in the past. The extracted burn temperatures showed good agreement with those determined from a complementary reflectance FTIR study.
An alternate representation of the geomagnetic core field obtained using machine learning
Authors: Kuslits Lukács , Horváth András , Wesztergom Viktor , Beggan Ciaran , Rubóczki Tibor , Prácser Ernő , Czirok Lili , Bozsó István , Lemperger István
Published: May 2024

Machine learning (ML) as a tool is rapidly emerging in various branches of contemporary geophysical research. To date, however, rarely has it been applied specifically for the study of Earth’s internal magnetic field and the geodynamo. Prevailing methods currently used in inferring the characteristic properties and the probable time evolution of the geodynamo are mostly based on reduced representations of magnetohydrodynamics (MHD). This study introduces a new inference method, referred to as Current Loop-based UNet Model Segmentation Inference (CLUMSI). Its long-term goal focuses on uncovering concentrations of electric current densities inside the core as the direct sources of the magnetic field itself, rather than computing the fluid motion using MHD. CLUMSI relies on simplified models in which equivalent current loops represent electric current systems emerging in turbulent geodynamo simulations. Various configurations of such loop models are utilized to produce synthetic magnetic field and secular variation (SV) maps computed at the core–mantle boundary (CMB). The resulting maps are then presented as training samples to an image-processing neural network designed specifically for solving image segmentation problems. This network essentially learns to infer the parameters and configuration of the loops in each model based on the corresponding CMB maps. In addition, with the help of the Domain Adversarial Training of Neural Networks (DANN) method during training, historical geomagnetic field data could also be considered alongside the synthetic samples. This implementation can increase the likelihood that a network trained primarily on synthetic data will appropriately handle real inputs. Our results focus mainly on the method's feasibility when applied to synthetic data and the quality of these inferences. A single evaluation of the trained network can recover the overall distribution of loop parameters with reasonable accuracy. To better represent conditions in the outer core, the study also proposes a computationally feasible process to account for magnetic diffusion and the corresponding induced currents in the loop models. However, the quality of the reconstruction of magnetic field properties is compromised by occasional poor inferences, and an inability to recover realistic SV.

Graphical Abstract
eTFC-01: a dual-labeled chelate-bridged tracer for SSTR2-positive tumors
Authors: Chapeau Dylan , Beekman Savanne , Handula Maryana , Murce Erika , de Ridder Corrina , Stuurman Debra , Seimbille Yann
Published: May 2024

Background

Integrating radioactive and optical imaging techniques can facilitate the prognosis and surgical guidance for cancer patients. Using a single dual-labeled tracer ensures consistency in both imaging modalities. However, developing such molecule is challenging due to the need to preserve the biochemical properties of the tracer while introducing bulky labeling moieties. In our study, we designed a trifunctional chelate that facilitates the coupling of the targeting vector and fluorescent dye at opposite sites to avoid undesired steric hindrance effects. The synthesis of the trifunctional chelate N3-Py-DOTAGA-(tBu)3 (7) involved a five-step synthetic route, followed by conjugation to the linear peptidyl-resin 8 through solid-phase synthesis. After deprotection and cyclization, the near-infrared fluorescent dye sulfo-Cy.5 was introduced using copper free click chemistry, resulting in eTFC-01. Subsequently, eTFC-01 was labeled with [111In]InCl3. In vitro assessments of eTFC-01 binding, uptake, and internalization were conducted in SSTR2-transfected U2OS cells. Ex-vivo biodistribution and fluorescence imaging were performed in H69-tumor bearing mice.

Results

eTFC-01 demonstrated a two-fold higher IC50 value for SSTR2 compared to the gold standard DOTA-TATE. Labeling of eTFC-01 with [111In]InCl3 gave a high radiochemical yield and purity. The uptake of [111In]In-eTFC-01 in U2OS.SSTR2 cells was two-fold lower than the uptake of [111In]In-DOTA-TATE, consistent with the binding affinity. Tumor uptake in H69-xenografted mice was lower for [111In]In-eTFC-01 at all-time points compared to [111In]In-DOTA-TATE. Prolonged blood circulation led to increased accumulation of [111In]In-eTFC-01 in highly vascularized tissues, such as lungs, skin, and heart. Fluorescence measurements in different organs correlated with the radioactive signal distribution.

Conclusion

The successful synthesis and coupling of the trifunctional chelate to the peptide and fluorescent dye support the potential of this synthetic approach to generate dual labeled tracers. While promising in vitro, the in vivo results obtained with [111In]In-eTFC-01 suggest the need for adjustments to enhance tracer distribution.
In vitro and in vivo evaluation of a tetrazine-conjugated poly-L-lysine effector molecule labeled with astatine-211
Authors: Timperanza Chiara , Jensen Holger , Hansson Ellinor , Bäck Tom , Lindegren Sture , Aneheim Emma
Published: May 2024

Background

A significant challenge in cancer therapy lies in eradicating hidden disseminated tumor cells. Within Nuclear Medicine, Targeted Alpha Therapy is a promising approach for cancer treatment tackling disseminated cancer. As tumor size decreases, alpha-particles gain prominence due to their high Linear Energy Transfer (LET) and short path length. Among alpha-particle emitters, 211At stands out with its 7.2 hour half-life and 100% alpha emission decay. However, optimizing the pharmacokinetics of radiopharmaceuticals with short lived radionuclides such as 211At is pivotal, and in this regard, pretargeting is a valuable tool. This method involves priming the tumor with a modified monoclonal antibody capable of binding both the tumor antigen and the radiolabeled carrier, termed the “effector molecule. This smaller, faster-clearing molecule improves efficacy. Utilizing the Diels Alder click reaction between Tetrazine (Tz) and Trans-cyclooctene (TCO), the Tz-substituted effector molecule combines seamlessly with the TCO-modified antibody. This study aims to evaluate the in vivo biodistribution of two Poly-L-Lysine-based effector molecule sizes (10 and 21 kDa), labelled with 211At, and the in vitro binding of the most favorable polymer size, in order to optimize the pretargeted radioimmunotherapy with 211At.

Results

In vivo results favor the smaller polymer’s biodistribution pattern over the larger one, which accumulates in organs like the liver and spleen. This is especially evident when comparing the biodistribution of the smaller polymer to a directly labelled monoclonal antibody. The smaller variant also shows rapid and efficient binding to SKOV-3 cells preloaded with TCO-modified Trastuzumab in vitro, emphasizing its potential. Both polymer sizes showed equal or better in vivo stability of the astatine-carbon bond compared to a monoclonal antibody labelled with the same prosthetic group.

Conclusions

Overall, the small Poly-L-Lysine-based effector molecule (10 kDa) holds the most promise for future research, exhibiting significantly lower uptake in the kidneys and spleen compared to the larger effector (21 kDa) while maintaining an in vivo stability of the astatine-carbon bond comparable to or better than intact antibodies. A proof of concept in vitro cell study demonstrates rapid reaction between the small astatinated effector and a TCO-labelled antibody, indicating the potential of this novel Poly-L-Lysine-based pretargeting system for further investigation in an in vivo tumor model.
Schlieren imaging and video classification of alphabet pronunciations: exploiting phonetic flows for speech recognition and speech therapy
Authors: Talaat Mohamed , Barari Kian , Si Xiuhua April , Xi Jinxiang
Published: May 2024

Speech is a highly coordinated process that requires precise control over vocal tract morphology/motion to produce intelligible sounds while simultaneously generating unique exhaled flow patterns. The schlieren imaging technique visualizes airflows with subtle density variations. It is hypothesized that speech flows captured by schlieren, when analyzed using a hybrid of convolutional neural network (CNN) and long short-term memory (LSTM) network, can recognize alphabet pronunciations, thus facilitating automatic speech recognition and speech disorder therapy. This study evaluates the feasibility of using a CNN-based video classification network to differentiate speech flows corresponding to the first four alphabets: /A/, /B/, /C/, and /D/. A schlieren optical system was developed, and the speech flows of alphabet pronunciations were recorded for two participants at an acquisition rate of 60 frames per second. A total of 640 video clips, each lasting 1 s, were utilized to train and test a hybrid CNN-LSTM network. Acoustic analyses of the recorded sounds were conducted to understand the phonetic differences among the four alphabets. The hybrid CNN-LSTM network was trained separately on four datasets of varying sizes (i.e., 20, 30, 40, 50 videos per alphabet), all achieving over 95% accuracy in classifying videos of the same participant. However, the network’s performance declined when tested on speech flows from a different participant, with accuracy dropping to around 44%, indicating significant inter-participant variability in alphabet pronunciation. Retraining the network with videos from both participants improved accuracy to 93% on the second participant. Analysis of misclassified videos indicated that factors such as low video quality and disproportional head size affected accuracy. These results highlight the potential of CNN-assisted speech recognition and speech therapy using articulation flows, although challenges remain in expanding the alphabet set and participant cohort.
Phytochemical analysis and evaluation of antibacterial activity of various extracts from leaves, stems and roots of Thalictrum foliolosum
Authors: Mishra Manoj Kumar
Published: May 2024

Background

Thalictrum foliolosum, a member of the Ranunculus family, is recognized for its therapeutic potential in addressing gastric issues, dyspepsia, tooth pain, abdominal colic pain, and piles. The diverse array of secondary metabolites present in the plant contributes to these therapeutic applications. This study aims to uncover and quantify the bioactive secondary metabolites found in the unexplored leaves, stems, and roots of T. foliolosum. Additionally, we also aimed to evaluate the antibacterial activity and MIC values of these extracts against a panel of pathogenic bacteria, such as pathogenic strains, including Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutant and Staphylococcus aureus.

Result

HPLC analysis suggested all examined compounds were found significantly more in root parts of plant. To determine the potential antimicrobial activity of different plant parts result suggested chloroform fraction of root most effective with variable potency against each examined pathogen at 25–100 µg/ml extracts which indicated rich content of berberine in this fraction. Minimum MIC (121.26 µg/mL) of the chloroform fraction of the root was also supported the results. Fatty acid methyl ester analysis by gas chromatography revealed that the stem contained high levels of fatty acids, such as palmitic acid, stearic acid, and linolenic acid, all of which have antibacterial properties.

Conclusion

The potential antimicrobial activity of extracts of various plant parts strongly supports the T. foliolosum plant's widespread use in folk medicine for the treatment of various chronic diseases and adulterants with various associated medicinal plant species.