bluuebunny/crossref_metadata_2025 huggingface dataset:
The non-specific lethal complex regulates genes and pathways genetically linked to Parkinson’s disease
Authors: Hicks Amy R , Reynolds Regina H , O’Callaghan Benjamin , García-Ruiz Sonia , Gil-Martínez Ana Luisa , Botía Juan , Plun-Favreau Hélène , Ryten Mina
Published: July 2023

Genetic variants conferring risks for Parkinson’s disease have been highlighted through genome-wide association studies, yet exploration of their specific disease mechanisms is lacking. Two Parkinson’s disease candidate genes, KAT8 and KANSL1, identified through genome-wide studies and a PINK1-mitophagy screen, encode part of the histone acetylating non-specific lethal complex. This complex localizes to the nucleus, where it plays a role in transcriptional activation, and to mitochondria, where it has been suggested to have a role in mitochondrial transcription. In this study, we sought to identify whether the non-specific lethal complex has potential regulatory relationships with other genes associated with Parkinson’s disease in human brain.

Correlation in the expression of non-specific lethal genes and Parkinson’s disease-associated genes was investigated in primary gene co-expression networks using publicly-available transcriptomic data from multiple brain regions (provided by the Genotype-Tissue Expression Consortium and UK Brain Expression Consortium), whilst secondary networks were used to examine cell type specificity. Reverse engineering of gene regulatory networks generated regulons of the complex, which were tested for heritability using stratified linkage disequilibrium score regression. Prioritized gene targets were then validated in vitro using a QuantiGene multiplex assay and publicly-available chromatin immunoprecipitation-sequencing data.

Significant clustering of non-specific lethal genes was revealed alongside Parkinson’s disease-associated genes in frontal cortex primary co-expression modules, amongst other brain regions. Both primary and secondary co-expression modules containing these genes were enriched for mainly neuronal cell types. Regulons of the complex contained Parkinson’s disease-associated genes and were enriched for biological pathways genetically linked to disease. When examined in a neuroblastoma cell line, 41% of prioritized gene targets showed significant changes in mRNA expression following KANSL1 or KAT8 perturbation. KANSL1 and H4K8 chromatin immunoprecipitation-sequencing data demonstrated non-specific lethal complex activity at many of these genes.

In conclusion, genes encoding the non-specific lethal complex are highly correlated with and regulate genes associated with Parkinson’s disease. Overall, these findings reveal a potentially wider role for this protein complex in regulating genes and pathways implicated in Parkinson’s disease.
Transgastric drainage of the perforated esophagus: our experiences over 10 years
Authors: Lunt Adam J , Ariyarathenam Arun , Chan David , Humphreys Lee , Sanders Grant , Wheatley Tim , Berrisford Richard G
Published: July 2023

We first described the technique of transgastric drainage of esophageal injuries in 2008. The method establishes vacuum drainage of the lumen of the esophagus, while maintaining patency, effectively exteriorizing the perforation to allow healing. We summarize this technique and present our experiences from the largest published series of patients. Our unit has treated selected esophageal injuries with transgastric drainage for 10 years. Indications include perforations not amenable to primary repair and treatment failure following prior surgical intervention. A 36 French silastic chest drain is pulled through the abdominal and stomach wall and introduced into the esophagus so that it crosses the perforation. Gastropexy is performed. Mediastinal decontamination and drainage are performed as needed. Continuous suction of −10 cm water is applied. Leak resolution is assessed with weekly water-soluble swallows. For this retrospective observational study, we analyzed data for patients with esophageal perforation, between 2012 and 2022. Inpatient mortality and time to leak resolution were set as primary and secondary outcomes. Esophageal perforations were treated with transgastric drain in 35 patients, of whom 68% (n = 24) were men. Median age was 67 (26–84). Spontaneous perforations accounted for 60% (n = 21), 31% (n = 11) were iatrogenic and 6% (n = 2) were ischemic. Inpatient and 30-day mortality was 14% (n = 5). Among successful treatments, the median length to resolution of leak on imaging was 34.5 days (6–80). Transgastric drainage can successfully treat esophageal perforations, where primary repair is not feasible. The mortality rate of 14% and reduced morbidity compares favorably with other traditional methods of management for esophageal perforation.
Addressing automatic speech recognition for ELT from a Global Englishes perspective
Authors: Lee Seongyong , Jeon Jaeho
Published: July 2023

Research has indicated that L2 learners frequently encounter challenges when using automatic speech recognition (ASR) in ELT. Therefore, this study explored how critical inquiries into the current ASR technology that is oriented towards native speech might elicit Global Englishes (GE) awareness among Korean pre-service teachers. Qualitative data gathered from interviews with twenty-three Korean students in a teacher education programme and their reflective journals revealed their GE awareness regarding ASR issues in ELT. Furthermore, the findings suggested that their GE awareness was influenced by their previous experiences with taking GE-informed courses and English as a lingua franca communication. Finally, these participants would be willing to incorporate GE perspectives into their future ASR-based ELT classes. It is suggested that the inclusion of GE perspectives into ELT courses be considered to encourage L2 students not to entirely conform to NS norms in ELT.
INFORM-AF: a pilot-feasibility study of an mHealth atrial fibrillation education program
Authors: Ferguson C , Shaikh F , Hickman L , Inglis S C , Bajorek B V , Downie A , Griffin K , Wynne R
Published: July 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council (Australian Government)

Objective

to determine the feasibility and efficacy of a digital education program for patients living with atrial fibrillation on patient knowledge and AF-related quality of life.

Methods

a single-arm pilot-feasibility study was conducted. Participants with diagnosed AF were recruited from two metropolitan hospitals in Australia, following index hospitalisation. INFORM-AF was delivered by a QStream digital platform directly to participant’s smartphones over 6 weeks. The intervention consisted of a series of 6 interactive micro-learning case studies, multiple choice questions, instant feedback and learning resources delivered using a standardised spaced algorithm with repetition. Topics addressed AF symptoms, risk factors and complications, lifestyle and medication management and seeking assistance. Outcome measures included AF knowledge (JEKQ), AF quality of life (AFEQT) and system usability (SUS). Surveys were completed at in-hospital baseline and via phone at 6 weeks, 3, 6 and 12 months.

Results

32 participants were enrolled, 2 were lost to follow up and 2 withdrew. 28 were included in the analyses. The mean age was 61 years (32-79 years), with 56% female. There were significant improvements to AF knowledge (62% pre vs 73% post, p<0.001) and AF quality of life at 6 weeks (54 pre and 68 post, p = 0.016), system usability was excellent (mean 84). Knowledge improvements were the greatest in the risk factor, symptom recognition, and when to seek assistance domains.

Conclusion

INFORM-AF demonstrated good feasibility with significant improvements in AF knowledge and quality of life at 12 months. We plan to evaluate this intervention in a larger clinical trial on outcomes including emergency department visits, hospitalisation and healthcare utilisation.Table 1Figure 1
Do ethnic minorities improve in exercise capacity following cardiac rehabilitation? a secondary analysis
Authors: Candelaria D , Duggan S , Zhang L , Gallagher R
Published: July 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SOLVE-CHD NHMRC Grant

Background/Introduction

Ethnic minorities experience higher rates of cardiovascular disease risks due to a combination of risk factors and socio-cultural influences. While comprehensive cardiac rehabilitation (CR) has well-established benefits for reducing mortality, morbidity, and improving physical fitness, little is known about exercise capacity outcomes for ethnic minorities following CR.

Purpose

This secondary analysis of data from an observational study aimed to evaluate exercise capacity outcomes of ethnic minorities following CR using 6-minute walk test (6MWT) or metabolic equivalent of task (METs) and to compare it to the majority group. Multiple linear regression models were used to determine if ethnic minority status was an independent predictor of change in 6MWT and METs after adjusting for baseline characteristics (age, sex, diagnosis, smoking, referral site, and wait time). Additionally, a binary logistic regression model was created for completers versus non-completers accounting for baseline variables.

Results

Participants totalled 2335, of which 326 (14%) were ethnic minorities. The mean age of ethnic minorities was 66.46 (SD 12.12) years, with 228 (70%) males. The most common referral diagnosis was myocardial infarction (27%), angina (25%), other – arrhythmias, cardiac devices, valve diseases/procedures (24%), and cardiac surgery (24%). Ethnic minorities had significantly lower 6MWT scores at baseline compared to the majority (379.9 (SD 118) versus 430.7 (SD 103) meters, p<0.001, but METs were comparable (6.69 (SD 2.73) versus 6.46 (SD 2.28) mg/kg/min, p = 0.69.

At CR completion, improvements in 6MWT were equivalent for minority (71.03 (SD 58.57)) and majority (71.37 (SD 61.16)) groups (p = 0.96), as well as METs (minority 3.01 (SD 1.66) versus majority 3.13 (SD 1.74) p = 0.77). Minority status was not an independent predictor of change in 6MWT and METs after accounting for age, sex, diagnosis, smoking, referral site, and wait time. However, participants that were minorities were half as likely to complete (OR 0.49 95% CI 0.38, 0.65).

Conclusion

Ethnic minorities achieve equivalent improvements in exercise capacity to majority participants following CR. These findings add to the effectiveness evidence of CR, at least for exercise capacity, for diverse populations. However, such benefits would only be gained with adequate participation and CR program completion, which remains poor for ethnic minorities. Improving CR program uptake and completion for ethnic minorities with cardiovascular disease should be prioritised.
The significant value of educated nurse in ECG Holter monitoring interpretation
Authors: Dimishkovska S , Lazevska M L , Tasevska V T , Ignatova B I , Josevska I J , Alii N A , Zafirovska D Z , Klincheva M K , Mitrev Z M
Published: July 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

ECG Holter monitoring is a non-invasive diagnostic procedure that continuously records electrocardiography during 24 hours daily routine. The primary role of the nurse is to secure that the electrodes are placed correctly, and to advise the patient.

Purpose

The aim of our study is to emphasize the great importance of nurses by involving them into the interpretation of ECG Holter monitoring.

Materials and Methods

Senior nurses in our hospital, R. Macedonia were educated, by cardiologists, in electrocardiography interpretation. The nurses proactively ensured the technical quality of the monitoring and the data processing. We analyzed the time from the setting up the 24 hours ECG Holter monitoring to the time when the results were issued to the patient in the period from January 2020 to December 2022. All data used for the study were taken from the Hospital Information System. Our Hospital Information System records the date and exact time (hours and minutes) of the opening and closing of the report. Only the referred cardiologist is authorized to close the report.

Results

Three thousand twenty-three 24 hours ECG Holter monitoring reports were processed. The average time of closing the report was 1680 minutes or 28 hours. If we exclude in average the first 22 hours of wearing the device, then we can conclude that the time from when the device is disconnected from the patient to the completion of the report, including the physician examination is in average 6 hours.

Conclusion

ECG educated nurses can be actively involved in the interpretation of ECG Holter monitoring which reduces the time for obtaining the results to less than 24 hours and enables rapid diagnosis and treatment by a cardiologist/electrophysiologist.
Quality assuring an outsourced ambulatory electrocardiogram pathway
Authors: Amarin M , Issa M , Malcolmson J , Stain N
Published: July 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

The rising demand for arrhythmia care has led to the use of outsourced ambulatory electrocardiogram (ECG) pathways to maintain timely service delivery and meet diagnostic targets. Since COVID-19, our ambulatory ECG service operates primarily through external third-party providers, using the remote (postal) model, where monitors are dispatched to patients for self-application. This pathway was activated to comply with social distancing restrictions and has now been integrated into our diagnostic model of care. A quality assurance (QA) process was introduced to ensure compliance with our internal ECG reporting practice and escalation protocols.

Purpose

To quality assure our outsourced ambulatory ECG reports and pathways against internal practices and protocols.

Methods

We audited our QA records on outsourced services from 1st January 2022 - 31st December 2022. During this period, a total of 4317 patients were provided with an ambulatory ECG monitor via the remote service. We conducted regular (~every 2-3 months) retrospective random sampling of ambulatory ECG reports (~10%) for inclusion in QA. Our QA framework consists of a series of quality and consistency checks related to clinical information, report content, and adherence to escalation protocols (table 1). QA reports are fed back to our providers at quarterly meetings to ensure improved service quality. To obtain the requisite data, a variety of sources were cross-referenced. These included our QA reports, outsourced databases, third-party provider platforms, and our patient information system.

Results

Over a 12-month period, a total of 459 reports were quality assured. Ambulatory ECG reports were checked for clinical information, report content, supporting ECG evidence and amendment requests (table 1). A compliance rate of 99% was achieved. There were few cases (1%) where a request was made to the provider to amend the report or include additional information, namely ECG strips to clarify the findings. We also quality checked compliance to our escalation protocols: appropriate RAG (red, amber, green) rating and action, timely notification to clinicians, and adequate documentation. The reviewed ambulatory ECG reports were RAG rated as: Red 23 (5%), Amber 189 (40%), Green-Amber 142 (30%), Green 117 (25%). These were carried out with 99% accuracy. Activation of the appropriate escalation protocols and timely clinician notification achieved 100% compliance, including 23 red-flagged reports requiring immediate action.

Conclusion

The outsourced ambulatory ECG pathway had a very high rate of compliance with internal ECG reporting practice and escalation protocols. Our QA framework ensures we work in collaboration with our external partners to continually provide high-quality ECG diagnostics. We believe undertaking internal quality checks is a vital part of using outsourced service providers.
Anxiety and depression in community-dwelling elders with cardiovascular risk factors
Authors: Sillero Sillero A , Fernandez-Elgueta A , Retamal-Matus H F , Marques-Sule E , Fuentes-Aparicio L , Moreno-Segura N O E M I , Lopez Dominguez J
Published: July 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Elders with three or more cardiovascular risk factors (CVRF) are at an increased risk of suffering a cardiac event. Anxiety and depression have been proven to be important outcomes in elders. This study aimed to compare the level of anxiety and depression in elders with three or more CVRF vs. elders with less than three CVRF.

Methods

This was a cross-sectional study. 112 community-dwelling elders participated in this study. Sociodemographic characteristics, (age, sex, marital status), clinical outcomes (systolic and diastolic blood pressure, heart rate) and CVRF (hypertension, diabetes, dyslipidaemia, smoking, personal and family history of cardiac events) were assessed. Participants were divided in two groups: i) elders with three or more CVRF (n=46); ii) elders with less than three CVRF (n=66). We evaluated anxiety and depression using the Hospital Anxiety and Depression Scale.

Results

The age of the sample ranged from 60 to 88 years, 71,4% were women, and 55,4% were married. The participants who presented at least three CVRF significantly showed a higher level of depression (HADS-D, p = 0,009) than those who presented less than three CVRF. However, no differences in anxiety (HADS-A, p = 0,087) were obtained when comparing between-group differences.

Conclusion

Elders with at least three CVRF might show higher levels of depression than elders with less than three CVRF. It seems important to measure depression when assessing cardiac outcomes in community-dwelling elders, in order to establish specific programs and treatments for elders who present CVRF.
A Nordic study of adolescents experiences of living with a parent having heart disease
Authors: Rotvig C , Berg S K , Andreasson F , Norekval T M , Stromberg A , Amofah H A , Holmbom M , Bernild C
Published: July 2023

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Novo Nordic Foundation

Background

An estimated 35% of heart disease occurs in individuals between 35 to 54 years of age, which is the prime child-bearing and parenting years. Even though heart disease often has a good prognosis, its treatment and symptoms can cause changes in everyday life within the family. Existing research shows that adolescents who live with a parent having serious illness are to a higher degree at risk of psychosocial, behavioural, and emotional challenges than peers if they are not accommodated. To our knowledge, limited research exists about adolescents´ experiences of living with parental heart disease.

Purpose

To explore how adolescents experience having a parent with heart disease.

Methods

This qualitative study is performed with semi-structured individual interviews guided by relevant theory. Interviews of 33 adolescents from 13 to 19 years old, who either had a mother or father with one of the diagnoses: ischemic heart disease, arrhythmia, heart failure, or cardiac arrest were conducted. Their parent had been ill for at least six months and up to 5 years and the study was carried out in Denmark, Norway, and Sweden from 2019 until 2022. The analysis was inspired by Reflexive methodology.

Results

The findings of the present study highlighted three central themes: Response to parental heart disease, Strategies in a changed life situation, and Altered relationships. While the heart was experienced as the most vital organ for adolescent’s feelings of fear of losing their parent both physically and mentally appeared and led to a range of different reactions. Adolescents pursued normality as a strategy to overcome their new life situation with parental heart disease where they prioritized a safe space to seek away from the disruption. Adolescents took adult responsibility at home, and through the process, enhanced maturity and new practical skills were developed.

Conclusion(s)

This study has contributed to new knowledge in regard to how parental heart disease changes everyday life as experienced by their young relatives. In order to reconstruct the adolescent’s new lives and cope with parental heart disease the adolescent’s pursued normality, which is a significant coping strategy that must be taken into account in relation to supporting them. To expand our knowledge more research is needed to explore what adolescents’ needs from healthcare professionals are.
Comparison of in-hospital outcomes and complications of left atrial appendage closure with the Watchman device between males and females
Authors: Alhuarrat Majd Al Deen , Pargaonkar Sumant , Rahgozar Kusha , Safiriyu Israel , Zhang Xiadong , Faillace Robert T , Di Biase Luigi
Published: July 2023

Aims

Left atrial appendage occlusion (LAAO) with WATCHMAN device is being used for patients with atrial fibrillation (AFB) and, as an off-label use, atrial flutter (AFL) who can't comply with long-term anticoagulation. We aim to study the differences in outcomes between sexes in patients undergoing Watchman device implantation.

Methodology

The National Inpatient Sample was queried between 2016 and 2019 using ICD-10 clinical modification codes I48x for AFB and AFL. Patients who underwent LAAO were identified using the procedural code 02L73DK. Comorbidities and complications were identified using ICD procedure and diagnosis codes. Differences in primary outcomes were analyzed using multivariable regression and propensity score matching.

Results

38 105 admissions were identified, of which 16 795 (44%) were females (76 ± 7.6 years) and 21 310 (56%) were males (75 ± 8 years). Females were more likely to have cardiac (frequencies: 5.8% vs 3.75%, aOR: 1.5 [1.35-1.68], p1 day inpatient (1.79 [1.67-1.93], P < 0.01) and be discharged to a facility (1.54 [1.33-1.80], P < 0.01).

Conclusion

Females are more likely to develop cardiac, renal, bleeding, pulmonary and TEE-related complications following LAAO procedure, while concurrently showing higher mortality, length of stay and discharge to facilities.
Understanding the Experiences of Family Caregivers of Nursing Home Residents With Dementia: A Grounded Theory Study
Authors: Piersol Catherine Verrier , Martínez Jenny , Chew Felicia , Perry Bonnie , Leland Natalie E
Published: July 2023

Background and Objectives

Alzheimer’s disease and related dementias progress over time and result in cognitive decline, loss of independence, and behavioral and psychiatric symptoms of dementia that can lead to nursing home placement. Research has focused on examining the effects of nursing home placement on the family caregiver; however, their experiences are less understood. We sought to investigate the experiences and perceptions of family caregivers of nursing home residents with dementia. The objective was to create a conceptual model that explains the complex nature of the family caregiver experience.

Research Design and Methods

This study is part of a larger randomized controlled trial. Following a grounded theory approach, we completed 30 in-depth, one-on-one interviews with family caregivers of nursing home residents with dementia. Data analysis followed an iterative process that employed open, axial, and selective coding.

Results

Our conceptual model depicts the interrelationship between contributing factors that interrelate and impact family caregiver satisfaction with nursing home care. Six factors contribute to family caregiver satisfaction: family caregiver interactions with nursing home staff; staff management of resident behavioral symptoms; nursing home context; family caregiver knowledge of dementia; family caregiver strain; and the resident experience.

Discussion and Implications

Our findings revealed family caregiver experiences that are unique to the institutional nursing home setting and not reflected in prior work focusing on experiences within community-based settings. Understanding family caregiver experiences and the contributors to how satisfaction in care is perceived, may foster collaboration and teamwork among families and staff.
Associations Between Family Caregiving and Romantic Relationships: An Exploratory Study With Nondistressed Couples Caring for an Outside Family Member
Authors: Cannon Christopher J , Barry Robin A
Published: July 2023

Background and Objectives

Family caregiving—providing emotional and physical health care for a family member or friend with an illness or disability—can result in many outcomes, including stress and beneficial experiences. Both romantic and caregiving relationships are complex and varied. Nevertheless, little research has examined how caregiving and romantic relationships influence one another. The purpose of this study was to understand ways romantic partners who care for a family member outside of their romantic relationship perceive that their romantic relationship and caregiving experiences influence one another.

Research Design and Methods

A qualitative study using thematic analysis was conducted. A sample of 5 couples where one or both partners were caring for a relative with dementia participated in interviews about their experiences in family caregiving and in their romantic relationship, as well as how the 2 roles interacted with each other. Couple members were interviewed separately and together.

Results

From these interviews, themes reflecting ways that caregiving influences romantic relationships, as well as ways romantic relationships influence caregiving emerged. Themes about caregiving influencing romantic relationships were caregiver stress interacting in the romantic relationship, the romantic relationship becoming less of a priority, and benefits experienced in the romantic relationship due to caregiving. Themes about romantic relationships influencing caregiving were partners improving the caregiving experience, and workload inequality.

Discussion and Implications

These findings broaden our understanding of how dyadic coping affects family caregiving and may suggest ways that the mutual influences caregivers experience between romantic relationships and caregiving benefits and challenges.
Mineral magnetic variation of the minle loess/palaeosol sequence of the late glacial to holocene period in the northeastern Tibetan Plateau
Authors: Xiong Jianguo , Zhong Yuezhi , Liu Caicai , Liu Qingri , Zhang Huiping , Deng Chenglong , Li Youli
Published: July 2023

Located at the modern junction of the Asian Summer Monsoon and the Westerlies, the northeastern Tibetan Plateau and western Chinese Loess Plateau are in distinct climatic setting from the middle and eastern Chinese Loess Plateau. Besides, Holocene climate variations near the Asian Summer Monsoon margin are highly debated with different models proposed. We carried out environmental magnetic analyses on the Minle loess section, with continuous deposition between 13.3–0.5 ka, located near this margin. Results show that the magnetic susceptibilities of palaeosols are dominantly contributed by superparamagnetic (SP) and single-domain (SD) maghemite and/or magnetite produced by pedogenesis. Limited changes in the content of haematite indicate that dust origin hardly influenced the magnetic mineral variations. The section is divided into four substages according to the changes in magnetic indices and provides a full scene of Holocene climatic evolutions. During the coldest and driest Late Glacial (13.3–11.7 ka), it displays the weakest pedogenesis, as suggested by the lowest SP and SD concentration. The strongest pedogenesis in the Minle section produced higher magnetic susceptibility than the loess records in the Chinese Loess Plateau during the early Holocene Optimum (11.7–8.1 ka). The subsequently declined summer insolation, equatorward migrated Westerlies and the weakened Asian Summer Monsoon led to weak pedogenesis during the middle Holocene (8.1–5.3 ka). Stronger pedogenesis during the late Holocene (5.3–0.5 ka) than the middle Holocene might be due to lower evapotranspiration from weaker insolation and/or to the enhanced winter Westerlies. We attribute the spatiotemporal differences in climatic records of the Chinese loess to precipitation, effective humidity and aeolian geomorphological processes.
Galectin-12 modulates Kupffer cell polarization to alter the progression of nonalcoholic fatty liver disease
Authors: Lee Jyun-Lin , Wang Yao-Chien , Hsu Yu-An , Chen Chih-Sheng , Weng Rui-Cian , Lu Yen-Pei , Chuang Chun-Yu , Wan Lei
Published: July 2023

Nonalcoholic fatty liver disease is caused by an imbalance in lipid metabolism and immune response to pose a risk factor for liver fibrosis. Recent evidence indicates that M2 macrophages secrete transforming growth factor-β1, which contributes to liver fibrosis. Galectin-12 has been demonstrated to regulate lipid metabolism and macrophage polarization. The purpose of this study is to investigate the role of galectin-12 in the development of nonalcoholic fatty liver disease and fibrosis. Liver tissue from wild-type C57BL/6 mice fed with a high-fat diet containing cholesterol and cholic acid for 4–12 weeks was used to examine galectin-12 expression and its correlation with nonalcoholic fatty liver disease. Furthermore, the effects of galectin-12 on M2 macrophages during the progression of nonalcoholic fatty liver disease were investigated by studying Kupffer cells from galectin-12 knockout mice and doxycycline-inducible Gal12−/–THP-1 cells. Ablation of galectin-12 promoted M2 polarization of Kupffer cells, as indicated by higher levels of M2 markers, such as arginase I and chitinase 3-like protein 3. Furthermore, the activation of signal transducer and activator of transcription 6 was significantly higher in Gal12−/− macrophages activated by interleukin-4, which was correlated with higher levels of transforming growth factor-β1. Moreover, Gal12−/− macrophage-conditioned medium promoted hepatic stellate cells myofibroblast differentiation, which was indicated by higher α-smooth muscle actin expression levels compared with those treated with LacZ control medium. Finally, we demonstrated that galectin-12 knockdown negatively regulated the suppressor of cytokine signaling 3 levels. These findings suggested that galectin-12 balances M1/M2 polarization of Kupffer cells to prevent nonalcoholic fatty liver disease progression.
Systematic Review and Meta-Analysis of the Use of Serum Leucine-Rich Alpha-2 Glycoprotein to Assess Crohn’s Disease Activity
Authors: Okita Muneyori , Nakashima Keita , Yamamura Takeshi , Matsui Shigeyuki
Published: July 2023

Background

Although fecal calprotectin is the most widely used biomarker for assessing Crohn’s disease activity, serum leucine-rich alpha-2 glycoprotein has recently attracted attention, especially in Japan. Here we performed a systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein to obtain evidence for its accuracy in assessing Crohn’s disease activity.

Methods

On February 1, 2023, we performed searches of PubMed, Web of Science, and CENTRAL. The Prospero number is CRD42023396034. The primary outcomes were the sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein for assessing Crohn’s disease activity. We used a bivariate generalized linear mixed model, assuming a binomial distribution at the test level and a bivariate normal distribution at the between-test level.

Results

We selected 9 studies involving 797 individuals in our systematic review. Regarding the primary outcomes, the synthesized sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein were 77.0% (95% confidence interval, 67.8% to 84.2%) and 81.1% (95% confidence interval, 72.6% to 87.4%), respectively. The area under the curve was 0.86, and the partial area under the curve was 0.78. Regarding between-study heterogeneity, both the I2 value by Zhou and Dendukuri approach and the I2 value by Holling sample size–adjusted approaches were 0%.

Conclusions

Our systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein demonstrated its accuracy in assessing Crohn’s disease activity. Further studies are needed to demonstrate its clinical utility and clinical validity.
What Do We Know about How Armed Conflict Affects Social Cohesion? A Review of the Empirical Literature
Authors: Fiedler Charlotte
Published: July 2023

How does armed conflict affect the social fabric of societies? This question is central if we want to understand better why some countries experience repeated cycles of violence. In recent years, considerable scientific work has been put into studying the social legacies of armed conflict. This article brings these academic studies together in a novel way, taking a holistic perspective and analyzing each of the three constituent elements of social cohesion—trust, cooperation, and identity—in detail and along both a vertical (state–society relations) and a horizontal (interpersonal and intergroup relations) dimension. Bringing together insights from fifty empirical studies, I call into question the initial optimism expressed by some scholars that conflict increases social cohesion. Only political participation seems to often be positively affected by experiencing conflict. In contrast, social and political trust as well as identification and cooperation across groups declines. However, research in several of these sub-elements of social cohesion is still nascent so that the strengths and shortcomings of the different studies are discussed and future avenues for research are identified.
The nuclear lamina is required for proper development and nuclear shape distortion in tomato
Authors: Blunt Endia L , Choi Junsik , Sussman Hayley , Christopherson Rachel C , Keen Patricia , Rahmati Ishka Maryam , Li Linda Y , Idrovo Joanna M , Julkowska Magdalena M , Van Eck Joyce , Richards Eric J
Published: July 2023

The nuclear lamina in plant cells is composed of plant-specific proteins, including nuclear matrix constituent proteins (NMCPs), which have been postulated to be functional analogs of lamin proteins that provide structural integrity to the organelle and help stabilize the three-dimensional organization of the genome. Using genomic editing, we generated alleles for the three genes encoding NMCPs in cultivated tomato (Solanum lycopersicum) to determine if the consequences of perturbing the nuclear lamina in this crop species were similar to or distinct from those observed in the model Arabidopsis thaliana. Loss of the sole NMCP2-class protein was lethal in tomato but is tolerated in Arabidopsis. Moreover, depletion of NMCP1-type nuclear lamina proteins leads to distinct developmental phenotypes in tomato, including leaf morphology defects and reduced root growth rate (in nmcp1b mutants), compared with cognate mutants in Arabidopsis. These findings suggest that the nuclear lamina interfaces with different developmental and signaling pathways in tomato compared with Arabidopsis. At the subcellular level, however, tomato nmcp mutants resembled their Arabidopsis counterparts in displaying smaller and more spherical nuclei in differentiated cells. This result argues that the plant nuclear lamina facilitates nuclear shape distortion in response to forces exerted on the organelle within the cell.
We need to talk about Candida tropicalis: Virulence factors and survival mechanisms
Authors: dos Santos Murilo Moreira , Ishida Kelly
Published: July 2023

Candida tropicalis is a notable species of the Candida genus representing an impressive epidemiology in tropical regions, especially in South America and Asia, where India already presents the species as the first in Candida epidemiology. Candida tropicalis has also shown a worrying antifungal resistance profile in recent years. It is essential to highlight that each pathogenic species of the Candida genus has a particular biology; however, Candida virulence factors are almost entirely based on studies with C. albicans. The intrinsic resistance of C. krusei to some azoles, the intrinsic osmotolerance of C. tropicalis, and the multidrug resistance of C. auris are just a few examples of how the biology of each Candida species is unique. Despite being a phylogenetically close species, C. tropicalis can support 15% NaCl, antagonistically metabolize and signal N-acetylglucosamine, encode 16 reported ALS genes, and other specificities discussed here compared to C. albicans. It is essential to clarify the details of the C. tropicalis infectious process, including identifying the participating secreted enzyme(s), the factors responsible for tissue damage, and the mechanisms underlying the morphogenesis and tolerance signaling pathways. In this review, we thoroughly assembled what is known about the main virulence factors of C. tropicalis, highlighting the missing pieces to stimulate further research with C. tropicalis and other non-Candida albicans species.
Identification of the simplest sugar-like molecule glycolaldehyde towards the hot molecular core G358.93–0.03 MM1
Authors: Manna Arijit , Pal Sabyasachi , Viti Serena , Sinha Sekhar
Published: July 2023

Glycolaldehyde (CH2OHCHO) is the simplest monosaccharide sugar in the interstellar medium, and it is directly involved in the origin of life via the ‘RNA world’ hypothesis. We present the first detection of CH2OHCHO towards the hot molecular core G358.93–0.03 MM1 using the Atacama Large Millimetre/Submillimetre Array (ALMA). The calculated column density of CH2OHCHO towards G358.93–0.03 MM1 is (1.52 ± 0.9) × 1016 cm−2 with an excitation temperature of 300 ± 68.5 K. The derived fractional abundance of CH2OHCHO with respect to H2 is (4.90 ± 2.92) × 10−9, which is consistent with that estimated by existing two-phase warm-up chemical models. We discuss the possible formation pathways of CH2OHCHO within the context of hot molecular cores and hot corinos and find that CH2OHCHO is likely formed via the reactions of radical HCO and radical CH2OH on the grain-surface of G358.93–0.03 MM1.
Quasi-periodic eruptions from mildly eccentric unstable mass transfer in galactic nuclei
Authors: Lu Wenbin , Quataert Eliot
Published: July 2023

We propose that the recently observed quasi-periodic eruptions (QPEs) in galactic nuclei are produced by unstable mass transfer due to Roche lobe overflow of a low-mass main-sequence star in a mildly eccentric (e ∼ 0.5) orbit. We argue that the QPE emission is powered by circularization shocks, but not directly by black hole (BH) accretion. Our model predicts the presence of a time-steady accretion disc that is bolometrically brighter than the time-averaged QPE luminosity, but primarily emits in the extreme-ultraviolet. This is consistent with the quiescent soft X-ray emission detected in between the eruptions in eROSITA QPE1, QPE2, and GSN 069. Such accretion discs have an unusual νLν ∝ ν12/7 optical spectrum. The lifetime of the bright QPE phase, 102–103 yr, is set by mass-loss triggered by ram-pressure interaction between the star and the accretion disc fed by the star itself. We show that the stellar orbits needed to explain QPEs can be efficiently created by the Hills breakup of tight stellar binaries provided that (i) the stellar binary orbit is tidally hardened before the breakup due to diffusive growth of the f-mode amplitude and (ii) the captured star’s orbit decays by gravitational wave emission without significant orbital angular momentum diffusion (which is the case for low-mass BHs, MBH ≲ 106 M⊙). We conclude by discussing the implications of our model for hyper-velocity stars, extreme mass ratio inspirals, repeating partial TDEs, and related stellar phenomena in galactic nuclei.
The MillenniumTNG Project: the impact of baryons and massive neutrinos on high-resolution weak gravitational lensing convergence maps
Authors: Ferlito Fulvio , Springel Volker , Davies Christopher T , Hernández-Aguayo César , Pakmor Rüdiger , Barrera Monica , White Simon D M , Delgado Ana Maria , Hadzhiyska Boryana , Hernquist Lars , Kannan Rahul , Bose Sownak , Frenk Carlos
Published: July 2023

We study weak gravitational lensing convergence maps produced from the MillenniumTNG simulations by direct projection of the mass distribution on the past backwards lightcone of a fiducial observer. We explore the lensing maps over a large dynamic range in simulation mass and angular resolution, allowing us to establish a clear assessment of numerical convergence. By comparing full physics hydrodynamical simulations with corresponding dark-matter-only runs, we quantify the impact of baryonic physics on the most important weak lensing statistics. Likewise, we predict the impact of massive neutrinos reliably far into the non-linear regime. We also demonstrate that the ‘fixed & paired’ variance suppression technique increases the statistical robustness of the simulation predictions on large scales not only for time slices but also for continuously output lightcone data. We find that both baryonic and neutrino effects substantially impact weak lensing shear measurements, with the latter dominating over the former on large angular scales. Thus, both effects must explicitly be included to obtain sufficiently accurate predictions for stage IV lensing surveys. Reassuringly, our results agree accurately with other simulation results where available, supporting the promise of simulation modelling for precision cosmology far into the non-linear regime.
Towards a full wCDM map-based analysis for weak lensing surveys
Authors: Zürcher D , Fluri J , Ajani V , Fischbacher S , Refregier A , Kacprzak T
Published: July 2023

The next generation of weak lensing surveys will measure the matter distribution of the local universe with unprecedented precision, allowing the resolution of non-Gaussian features of the convergence field. This encourages the use of higher-order mass-map statistics for cosmological parameter inference. We extend the forward-modelling based methodology introduced in a previous forecast paper to match these new requirements. We provide multiple forecasts for the $w$CDM parameter constraints that can be expected from stage 3 and 4 weak lensing surveys. We consider different survey setups, summary statistics and mass map filters including wavelets. We take into account the shear bias, photometric redshift uncertainties, and intrinsic alignment. The impact of baryons is investigated and the necessary scale cuts are applied. We compare the angular power spectrum analysis to peak and minima counts as well as Minkowski functionals of the mass maps. We find a preference for Starlet over Gaussian filters. Our results suggest that using a survey setup with 10 instead of 5 tomographic redshift bins is beneficial. Adding cross-tomographic information improves the constraints on cosmology and especially on galaxy intrinsic alignment for all statistics. In terms of constraining power, we find the angular power spectrum and the peak counts to be equally matched for stage 4 surveys, followed by minima counts and the Minkowski functionals. Combining different summary statistics significantly improves the constraints and compensates the stringent scale cuts. We identify the most ‘cost-effective’ combination to be the angular power spectrum, peak counts and Minkowski functionals following Starlet filtering.
The complex spectral behavior of the newly discovered neutron star X-ray binary Swift J1858.6-0814
Authors: Mondal Aditya S , Raychaudhuri B , Dewangan G C
Published: July 2023

We report on the NuSTAR observation of the newly discovered neutron star X-ray binary Swift J1858.6-0814 taken on 23rd March 2019. The light curve of the source exhibits several large flares during some time intervals of this observation. The source is softer in the high-intensity interval where the large flaring activity mainly occurs. We perform time-resolved spectroscopy on the source by extracting spectra for two different intensity intervals. The source was observed with a 3 − 79keV luminosity of ∼9.68 × 1036 ergs/s and ∼4.78 × 1036 ergs/s for high and low-intensity interval, respectively assuming a distance of 15 kpc. We find a large value of the absorbing column density ($\rm {N_{H}}\sim 1.1\times 10^{23}$ cm−2), and it appears to be uncorrelated with the observed flux of the source. Each spectrum shows evidence of Fe Kα emission in the 5 − 7keV energy band, an absorption edge around ∼7 − 8keV, and a broad Compton hump above 15keV, indicating the presence of a reflection spectrum. The observed features are well explained by the contribution of a relativistic reflection model and a partially covering absorption model. From the best-fit spectral model, we found an inner disc radius to be $4.87_{-0.96}^{+1.63}\,\,R_{ISCO}$ (for the high-intensity interval) and $5.68_{-2.78}^{+9.54}\,\,R_{ISCO}$ (for the low-intensity interval), indicating a significant disc truncation. The disk inclination is found to be relatively low, i < 330. We further place an upper limit on this source’s magnetic field strength considering the disc is truncated at the magnetospheric radius.
Detection of a strong ~2.5 Hz modulation in the newly discovered millisecond pulsar MAXI J1816–195
Authors: Li P P , Tao L , Zhang L , Bu Q C , Qu J L , Ji L , Wang P J , Chen Y P , Zhang S , Ma R C , Yang Z X , Ye W T , Zhao S J , Zhao Q C , Huang Y , Ma X , Qiao E L , Jia S M , Zhang S N
Published: July 2023

MAXI J1816–195 is a newly discovered accreting millisecond X-ray pulsar that went outburst in 2022 June. Through timing analysis with Neutron star Interior Composition Explorer (NICER) and Nuclear Spectroscopic Telescope Array (NuSTAR) observations, we find a transient modulation at ~2.5 Hz during the decay period of MAXI J1816–195. The modulation is strongly correlated with a spectral hardening, and its fractional rms amplitude increases with energy. These results suggest that the modulation is likely to be produced in an unstable corona. In addition, the presence of the modulation during thermonuclear bursts indicates that it may originate from a disc-corona where the optical depth is likely the main factor affecting the modulation, rather than temperature. Moreover, we find significant reflection features in the spectra observed simultaneously by NICER and NuSTAR, including a relativistically broadened Fe-K line around 6–7 keV, and a Compton hump in the 10–30 keV energy band. The radius of the inner disc is constrained to be Rin  = (1.04–1.23) RISCO based on reflection modeling of the broad-band spectra. Assuming that the inner disc is truncated at the magnetosphere radius, we estimate that the magnetic field strength is $\le 4.67 \times 10^{8}\, \rm G$.