bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel anthropometric indicators of visceral obesity predict the severity of hyperlipidemic acute pancreatitis
Authors: Zhu Yi , Huang Yingbao , Sun Houzhang , Chen Lifang , Yu Huajun , Shi Liuzhi , Xia Weizhi , Sun Xuecheng , Yang Yunjun , Huang Hang
Published: April 2024

Background

Obesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP.

Method

The body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test.

Results

Patients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678–0.784.

Conclusions

This study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP.
A mixed methods evaluation of the impact of ECHO® telementoring model for capacity building of community health workers in India
Authors: Panda Rajmohan , Lahoti Supriya , Mishra Nivedita , Prabhu Rajath R. , Singh Kalpana , Rai Apoorva Karan , Rai Kumud
Published: April 2024

Introduction

India has the largest cohort of community health workers with one million Accredited Social Health Activists (ASHAs). ASHAs play vital role in providing health education and promoting accessible health care services in the community. Despite their potential to improve the health status of people, they remain largely underutilized because of their limited knowledge and skills. Considering this gap, Extension for Community Healthcare Outcomes (ECHO)® India, in collaboration with the National Health System Resource Centre (NHSRC), implemented a 15-h (over 6 months) refresher training for ASHAs using a telementoring interface. The present study intends to assess the impact of the training program for improving the knowledge and skills of ASHA workers.

Methods

We conducted a pre–post quasi-experimental study using a convergent parallel mixed-method approach. The quantitative survey (n = 490) assessed learning competence, performance, and satisfaction of the ASHAs. In addition to the above, in-depth interviews with ASHAs (n = 12) and key informant interviews with other stakeholders (n = 9) examined the experience and practical applications of the training. Inferences from the quantitative and qualitative approaches were integrated during the reporting stage and presented using an adapted Moore’s Expanded Outcomes Framework.

Results

There was a statistically significant improvement in learning (p = 0.038) and competence (p = 0.01) after attending the training. Participants were satisfied with the opportunity provided by the teleECHO™ sessions to upgrade their knowledge. However, internet connectivity, duration and number of participants in the sessions were identified as areas that needed improvement for future training programs. An improvement in confidence to communicate more effectively with the community was reported. Positive changes in the attitudes of ASHAs towards patient and community members were also reported after attending the training. The peer-to-peer learning through case-based discussion approach helped ensure that the training was relevant to the needs and work of the ASHAs.

Conclusions

The ECHO Model ™ was found effective in improving and updating the knowledge and skills of ASHAs across different geographies in India. Efforts directed towards knowledge upgradation of ASHAs are crucial for strengthening the health system at the community level. The findings of this study can be used to guide future training programs.

Trial registration The study has been registered at the Clinical Trials Registry, India (CTRI/2021/10/037189) dated 08/10/2021.
The future burden of type 2 diabetes in Belgium: a microsimulation model
Authors: Mertens Elly , Ocira Junior , Sagastume Diana , Vasquez Maria Salve , Vandevijvere Stefanie , Peñalvo José L.
Published: April 2024

Objective

To forecast the annual burden of type 2 diabetes and related socio-demographic disparities in Belgium until 2030.

Methods

This study utilized a discrete-event transition microsimulation model. A synthetic population was created using 2018 national register data of the Belgian population aged 0–80 years, along with the national representative prevalence of diabetes risk factors obtained from the latest (2018) Belgian Health Interview and Examination Surveys using Multiple Imputation by Chained Equations (MICE) as inputs to the Simulation of Synthetic Complex Data (simPop) model. Mortality information was obtained from the Belgian vital statistics and used to calculate annual death probabilities. From 2018 to 2030, synthetic individuals transitioned annually from health to death, with or without developing type 2 diabetes, as predicted by the Finnish Diabetes Risk Score, and risk factors were updated via strata-specific transition probabilities.

Results

A total of 6722 [95% UI 3421, 11,583] new cases of type 2 diabetes per 100,000 inhabitants are expected between 2018 and 2030 in Belgium, representing a 32.8% and 19.3% increase in T2D prevalence rate and DALYs rate, respectively. While T2D burden remained highest for lower-education subgroups across all three Belgian regions, the highest increases in incidence and prevalence rates by 2030 are observed for women in general, and particularly among Flemish women reporting higher-education levels with a 114.5% and 44.6% increase in prevalence and DALYs rates, respectively. Existing age- and education-related inequalities will remain apparent in 2030 across all three regions.

Conclusions

The projected increase in the burden of T2D in Belgium highlights the urgent need for primary and secondary preventive strategies. While emphasis should be placed on the lower-education groups, it is also crucial to reinforce strategies for people of higher socioeconomic status as the burden of T2D is expected to increase significantly in this population segment.
A promising frontier: targeting NETs for stroke treatment breakthroughs
Authors: Fang Huijie , Bo Yunfei , Hao Zhongfei , Mang Ge , Jin Jiaqi , Wang Hongjun
Published: April 2024

Stroke is a prevalent global acute cerebrovascular condition, with ischaemic stroke being the most frequently occurring type. After a stroke, neutrophils accumulate in the brain and subsequently generate and release neutrophil extracellular traps (NETs). The accumulation of NETs exacerbates the impairment of the blood‒brain barrier (BBB), hampers neovascularization, induces notable neurological deficits, worsens the prognosis of stroke patients, and can facilitate the occurrence of t-PA-induced cerebral haemorrhage subsequent to ischaemic stroke. Alternative approaches to pharmacological thrombolysis or endovascular thrombectomy are being explored, and targeting NETs is a promising treatment that warrants further investigation.
Effect of S-region mutations on HBsAg in HBsAg-negative HBV-infected patients
Authors: Liu Hui , Chen Shuxiang , Liu Xin , Lou Jinli
Published: April 2024

Background

Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI.

Methods

Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism.

Results

Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure.

Conclusions

HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.
“Qi Nan” agarwood restores podocyte autophagy in diabetic kidney disease by targeting EGFR signaling pathway
Authors: Li Ning , Liu Xuenan , Wang Hao , Duan Yingling , Zhang Yu , Zhou Ping , Dai Haofu , Lan Tian
Published: April 2024

Background

Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus, contributing to end-stage renal disease with limited treatment options. The development of DKD is attributed to podocyte injury resulting from abnormal podocyte autophagy. Consequently, the restoration of podocyte autophagy is deemed a practicable approach in the treatment of DKD.

Methods

Diabetic mice were induced by streptozotocin and high-fat diet feeding. Following 8 weeks of “QN” agarwood treatment, metrics such as albuminuria, serum creatinine (Scr), and blood urea nitrogen (BUN) were evaluated. Renal histological lesions were evaluated by H&E, PAS, Masson, and Sirius red staining. Evaluation of the effects of “QN” agarwood on renal inflammation and fibrosis in DKD mice through WB, q-PCR, and IHC staining analysis. Cytoscape 3.7.1 was used to construct a PPI network. With the DAVID server, the gene ontology (GO) functional annotation and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the target enrichment were performed. Molecular docking and binding affinity calculations were conducted using AutoDock, while PyMOL software was employed for visualizing the docking results of active compounds and protein targets.

Results

The results of this study show that “QN” agarwood reduced albuminuria, Scr, and BUN in DKD mice, and improved the renal pathological process. Additionally, “QN” agarwood was observed to downregulate the mRNA and protein expression levels of pro-inflammatory and pro-fibrotic factors in the kidneys of DKD mice. Network pharmacology predicts that “QN” agarwood modulates the epidermal growth factor receptor (EGFR) signaling pathway. “QN” agarwood can increase the expression of LC3B and Nphs1 in DKD mice while reducing the expression of EGFR.

Conclusion

The present study demonstrated that “QN” agarwood ameliorated renal injury in DKD by targeting EGFR and restoring podocyte autophagy.

Graphical Abstract
Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression
Authors: Zhuang Wanzhen , Liu Chengxiu , Hong Yilin , Zheng Yue , Huang Minjian , Tang Haijun , Zhao Lilan , Huang Zhixin , Tu Mingshu , Yu Lili , Chen Jianlin , Zhang Yi , Chen Xiongfeng , Lin Fan , Gao Qi , Yu Chundong , Huang Yi
Published: April 2024

Background

Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood.

Methods

A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC.

Results

We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes.

Conclusions

NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.
Prevalence of airway patency and air pocket in critically buried avalanche victims - a scoping review
Authors: Eisendle Frederik , Rauch Simon , Wallner Bernd , Brugger Hermann , Strapazzon Giacomo
Published: April 2024

Introduction

Survival of critically buried avalanche victims is directly dependent on the patency of the airway and the victims’ ability to breathe. While guidelines and avalanche research have consistently emphasized on the importance of airway patency, there is a notable lack of evidence regarding its prevalence.

Objective

The aim of this review is to provide insight into the prevalence of airway patency and air pocket in critically buried avalanche victims.

Methods

A scoping review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline extension for scoping reviews. MEDLINE and Cochrane databases, as well as additional manual searching was performed to identify literature reporting data on airway patency and the presence of an air pocket in critically buried avalanche victims. After eliminating duplicates, we screened abstracts and main texts to identify eligible studies.

Results

Of 4,109 studies identified 154 were eligible for further screening. Twenty-four publications and three additional data sources with a total number of 566 cases were included in this review. The proportion of short-term (< 35 min) to long-term burial (≥ 35 min) in the analysed studies was 19% and 66%, respectively. The burial duration remained unknown in 12% of cases. The prevalence of airway patency in critically buried avalanche victims was 41% while that of airway obstruction was 12%, with an overall rate of reporting as low as 50%. An air pocket was present in 19% of cases, absent in 46% and unknown in 35% of the cases.

Conclusion

The present study found that in critically buried avalanche victims patent airways were more than three times more prevalent than obstructed, with the airway status reported only in half of the cases. This high rate of airway patency supports the ongoing development and the effectiveness of avalanche rescue systems which oppose asphyxiation in critically buried avalanche victims. Further effort should be done to improve the documentation of airway patency and the presence of an air pocket in avalanche victims and to identify factors affecting the rate of airway obstruction.
The ten “hard” questions in pediatric functional constipation
Authors: Fedele Flora , Fioretti Maria Teresa , Scarpato Elena , Martinelli Massimo , Strisciuglio Caterina , Miele Erasmo
Published: April 2024

Functional constipation is a common problem in childhood and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. No organic cause of the constipation can be found in approximately 95% of children, defining the “so-called” chronic functional constipation. Its prevalence has been reported to range from 0.7 to 29.6%, with a median of 12%. The diagnosis of functional constipation is exclusively clinical based on the pediatric diagnostic Rome criteria for functional gastrointestinal disorders and does not routinely require laboratory and/or radiological investigations. In case of alarm signs and symptoms that may suggest organic diseases, further investigations can be required. The therapeutic management is based on non-pharmacological and pharmacological approaches. Education, demystification of constipation and reward-based toilet training represent the cornerstones of nonpharmacological management. Disimpaction, maintenance treatment and weaning of medication are all elements of pharmacological treatment. Osmotic laxatives, mainly polyethylene glycol (PEG), are considered the first-choice laxative for both disimpaction and maintenance treatment. The aim of this review is to provide pediatric gastroenterologists with a practical tool to support the clinical and therapeutic management of children and adolescents affected by chronic functional constipation.
Point-of-care ultrasound (POCUS) pediatric resident training course: a cross-sectional survey
Authors: Lo Bianco Manuela , Presti Santiago , Finocchiaro Maria Carla , Trobia Gian Luca , Sciacca Tiziana Virginia , Cucuzza Maria Elena , Caudullo Elia , Calcara Giacomo , Ruggieri Martino , Di Stefano Vita Antonella
Published: April 2024

Background

Point-of-care ultrasound (POCUS) is becoming increasingly crucial in the Pediatric Emergency Department for objective patient examination. However, despite its growing interest and wide-ranging applications, POCUS remains relatively unexplored in general pediatric training and education. Many physicians still find it challenging to comprehend and implement.

Methods

A theoretical-practical POCUS course for pediatric residents was conducted at the University of Catania, Italy. The course’s effectiveness and practical impact on residents was assessed through a pre-post training survey. The first part of the questionnaire focused on the self-perceived time needed to learn how to recognize the following conditions using POCUS: (i) Pleural effusion (ii) Lung consolidation (iii) Pneumothorax (PNX) (iv) Cardiac contractility (v) Pericardial effusion (vi) Perisplenic effusion (vii) Morison’s pouch effusion (viii) Douglas’ pouch effusion (ix) Filling and collapsibility of the inferior vena cava. In the second part, we compared the potential role of POCUS in (i) Reducing the use of ionizing radiation in children (ii) Increasing the sense of security in diagnosis and treatment decisions making and (iii) Increasing the residents’ confidence level with POCUS after the course on a 1-to-10 rating scale.

Results

Seventy-two residents participated in the study. The statistical analysis showed significant pre-post differences in almost all the items considered, except for “cardiac contractility” and “PNX”. Furthermore, the perceived potential role of POCUS in reducing ionizing radiation usage and the sense of security in diagnosis and treatment decisions showed statistically significant differences (p < 0.05) before and after the course. Data analysis also revealed a consistently high confidence level with POCUS after the course.

Conclusions

The results highlight the importance of including a POCUS track course in pediatric post-graduate programs due to its simplicity, rapid learning time, and clinical usefulness. Based on these findings, it would be recommended to increase the teaching hours dedicated to the recognition of pneumothorax and cardiology POCUS examination. Emphasizing POCUS training in pediatric education can enhance patient care and diagnostic accuracy while minimizing radiation exposure.
Improving mental health in chronic care in general practice: study protocol for a cluster-randomised controlled trial of the Healthy Mind intervention
Authors: Søjbjerg Anne , Mygind Anna , Rasmussen Stinne Eika , Christensen Bo , Pedersen Anette Fischer , Maindal Helle Terkildsen , Burau Viola , Christensen Kaj Sparle
Published: April 2024

Background

Mental health issues are common among patients with chronic physical conditions, affecting approximately one in five patients. Poor mental health is associated with worse disease outcomes and increased mortality. Problem-solving therapy (PST) may be a suitable treatment for targeting poor mental health in these patients. This study protocol describes a randomised controlled trial of the Healthy Mind intervention, a general practice-based intervention offering PST to patients with type 2 diabetes and/or ischaemic heart disease and poor mental well-being.

Methods

A stepped-wedge cluster-randomised controlled trial with 1-year follow-up will be conducted in Danish general practice. At the annual chronic care consultation, patients with type 2 diabetes and/or chronic ischaemic heart disease will be screened for poor mental well-being. Patients in the control group will be offered usual care while patients in the intervention group will be offered treatment with PST provided by general practitioners (GPs) or general practice staff, such as nurses, who will undergo a 2-day PST course before transitioning from the control to the intervention group. The primary outcome is change in depressive symptoms after 6 and 12 months. Secondary outcomes include change in mental well-being, anxiety, and diabetes distress (patients with type 2 diabetes) after 6 and 12 months as well as change in total cholesterol levels, low-density lipoprotein (LDL) levels, and blood glucose levels (patients with diabetes) after 12 months. Process outcomes include measures of implementation and mechanisms of impact. We aim to include a total of 188 patients, corresponding to approximately 14 average-sized general practices.

Discussion

The Healthy Mind trial investigates the impact of PST treatment for patients with chronic disease and poor mental well-being in general practice. This will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic diseases in general practice. The results of this study will provide relevant insights to aid GPs, and general practice staff manage patients with poor mental well-being.

Trial registration

ClinicalTrials.gov NCT05611112. Registered on October 28, 2022.
Development and validation of a pulmonary function test data extraction tool for the US department of veterans affairs electronic health record
Authors: Rabin Alexander S. , Weinstein Julien B. , Seelye Sarah M. , Whittington Taylor N. , Hogan Cainnear K. , Prescott Hallie C.
Published: April 2024

Objective

Pulmonary function test (PFT) results are recorded variably across hospitals in the Department of Veterans Affairs (VA) electronic health record (EHR), using both unstructured and semi-structured notes. We developed and validated a hospital-specific code to extract pre-bronchodilator measures of obstruction (ratio of forced expiratory volume in one second [FEV1] to forced vital capacity [FVC]) and severity of obstruction (percent predicted of FEV1).

Results

Among 36 VA facilities with the most PFTs completed between 2018 and 2022 from a parent cohort of veterans receiving long-acting controller inhalers, 12 had a consistent syntactical convention or template for reporting PFT data in the EHR. Of the 42,718 PFTs identified from these 12 facilities, the hospital-specific text processing pipeline yielded 24,860 values for the FEV1:FVC ratio and 23,729 values for FEV1. A ratio of FEV1:FVC less than 0.7 was identified in 17,615 of 24,922 studies (70.7%); 8864 of 24,922 (35.6%) had a severe or very severe reduction in FEV1 (< 50% of the predicted value). Among 100 randomly selected PFT reports reviewed by two pulmonary physicians, the coding solution correctly identified the presence of obstruction in 99 out of 100 studies and the degree of obstruction in 96 out of 100 studies.
Machine learning security and privacy: a review of threats and countermeasures
Authors: Paracha Anum , Arshad Junaid , Farah Mohamed Ben , Ismail Khalid
Published: April 2024

Machine learning has become prevalent in transforming diverse aspects of our daily lives through intelligent digital solutions. Advanced disease diagnosis, autonomous vehicular systems, and automated threat detection and triage are some prominent use cases. Furthermore, the increasing use of machine learning in critical national infrastructures such as smart grids, transport, and natural resources makes it an attractive target for adversaries. The threat to machine learning systems is aggravated due to the ability of mal-actors to reverse engineer publicly available models, gaining insight into the algorithms underpinning these models. Focusing on the threat landscape for machine learning systems, we have conducted an in-depth analysis to critically examine the security and privacy threats to machine learning and the factors involved in developing these adversarial attacks. Our analysis highlighted that feature engineering, model architecture, and targeted system knowledge are crucial aspects in formulating these attacks. Furthermore, one successful attack can lead to other attacks; for instance, poisoning attacks can lead to membership inference and backdoor attacks. We have also reviewed the literature concerning methods and techniques to mitigate these threats whilst identifying their limitations including data sanitization, adversarial training, and differential privacy. Cleaning and sanitizing datasets may lead to other challenges, including underfitting and affecting model performance, whereas differential privacy does not completely preserve model’s privacy. Leveraging the analysis of attack surfaces and mitigation techniques, we identify potential research directions to improve the trustworthiness of machine learning systems.
Severe enduring anorexia nervosa (SE-AN) treatment options and their effectiveness: a review of literature
Authors: Marcolini Federica , Ravaglia Alessandro , Tempia Valenta Silvia , Bosco Giovanna , Marconi Giorgia , De Ronchi Diana , Atti Anna Rita
Published: April 2024

Introduction

 For nearly 20% of patients diagnosed with Anorexia Nervosa (AN), the eating disorder (ED) is prolonged and becomes long-lasting. It has been reported that patients diagnosed with Severe Enduring Anorexia Nervosa (SE-AN) have worse ED symptoms, higher rates of lifetime hospitalization, and lower psychosocial well-being compared to patients with shorter disease duration.

Objectives

 This review aims to describe the treatments proposed to date and their effectiveness on SE-AN-related outcomes.

Methods

 We conducted a PubMed search for studies addressing the issue of treatment approach to SE-AN adults, that were published between 2003 and 2023, peer-reviewed, written in the English language, and available in full-text. Next, we inductively created relevant macro-themes by synthesizing the data from the included articles.

Results

 Of 251 PubMed studies, 25 articles were considered for data extraction, all published between 2003 and 2022. We identified three macro-themes. The first macro-theme, “Psychotherapy”, mostly takes into consideration treatment effectiveness of cognitive behavioral therapy (CBT). Various reports determined its greater effectiveness compared to Specialist Supportive Clinical Management (SSCM), and one study proved that outpatient CBT is a valid alternative to hospitalization. The second one involves “Pharmacological Treatments”. Research on dronabinol, a synthetic orexigenic cannabinoid, antipsychotics (in particular, olanzapine and haloperidol), and ketamine showed some mixed results regarding the often-complementary areas of weight gain and improvement in ED-related symptoms. Regarding the third macro-theme, “Brain Stimulation Therapies,” such as Repetitive Transcranial Magnetic Stimulation (rTMS) and Deep Brain Stimulation (DBS), we found promising results in improving ED-related psychological traits (such as mood and anxiety), affective regulation, and quality of life. However, we have observed divergent results regarding outcome measures such as BMI and weight gain.

Conclusions

 SE-AN patients are predicted to encounter both medical complications and psychological distress of increasing severity that will inevitably affect their quality of life; to our knowledge, research evidence on treatment options for SE-AN remains limited, and the methodological quality of studies is generally low. These findings denote the need to focus future research efforts on effective treatment strategies specific to long-lasting EDs.
MicroRNAs predict early complications of autologous hematopoietic stem cell transplantation
Authors: Mikulski Damian , Nowicki Mateusz , Dróżdż Izabela , Perdas Ewelina , Strzałka Piotr , Kościelny Kacper , Misiewicz Małgorzata , Stawiski Konrad , Wierzbowska Agnieszka , Fendler Wojciech
Published: April 2024

Autologous hematopoietic stem cell transplantation (AHSCT) remains the most prevalent type of stem cell transplantation. In our study, we investigated the changes in circulating miRNAs in AHSCT recipients and their potential to predict early procedure-related complications. We collected serum samples from 77 patients, including 54 with multiple myeloma, at four key time points: before AHSCT, on the day of transplantation (day 0), and at days + 7 and + 14 post-transplantation. Through serum miRNA-seq analysis, we identified altered expression patterns and miRNAs associated with the AHSCT procedure. Validation using qPCR confirmed deviations in the levels of miRNAs at the beginning of the procedure in patients who subsequently developed bacteremia: hsa-miR-223-3p and hsa-miR-15b-5p exhibited decreased expression, while hsa-miR-126-5p had increased level. Then, a neural network model was constructed to use miRNA levels for the prediction of bacteremia. The model achieved an accuracy of 93.33% (95%CI: 68.05-99.83%), with a sensitivity of 100% (95%CI: 67.81-100.00%) and specificity of 90.91% (95%CI: 58.72-99.77%) in predicting bacteremia with mean of 6.5 ± 3.2 days before occurrence. In addition, we showed unique patterns of miRNA expression in patients experiencing platelet engraftment delay which involved the downregulation of hsa-let-7f-5p and upregulation of hsa-miR-96-5p; and neutrophil engraftment delay which was associated with decreased levels of hsa-miR-125a-5p and hsa-miR-15b-5p. Our findings highlight the significant alterations in serum miRNA levels during AHSCT and suggest the clinical utility of miRNA expression patterns as potential biomarkers that could be harnessed to improve patient outcomes, particularly by predicting the risk of bacteremia during AHSCT.
Immune escape of multiple myeloma cells results from low miR29b and the ensuing epigenetic silencing of proteasome genes
Authors: Leone Patrizia , Malerba Eleonora , Prete Marcella , Solimando Antonio Giovanni , Croci Giorgio Alberto , Ditonno Paolo , Tucci Marco , Susca Nicola , Derakhshani Afshin , Dufour Antoine , De Re Valli , Silvestris Nicola , Racanelli Vito
Published: April 2024

Background

Activation of CD28 on multiple myeloma (MM) plasma cells, by binding to CD80 and CD86 on dendritic cells, decreases proteasome subunit expression in the tumor cells and thereby helps them evade being killed by CD8+ T cells. Understanding how CD28 activation leads to proteasome subunit downregulation is needed to design new MM therapies.

Methods

This study investigates the molecular pathway downstream of CD28 activation, using an in vitro model consisting of myeloma cell lines stimulated with anti-CD28-coated beads.

Results

We show that CD28 engagement on U266 and RPMI 8226 cells activates the PI3K/AKT pathway, reduces miR29b expression, increases the expression of DNA methyltransferase 3B (DNMT3B, a target of miR29b), and decreases immunoproteasome subunit expression. In vitro transfection of U266 and RPMI 8226 cells with a miR29b mimic downregulates the PI3K/AKT pathway and DNMT3B expression, restores proteasome subunit levels, and promotes myeloma cell killing by bone marrow CD8+ T cells from MM patients. Freshly purified bone marrow plasma cells (CD138+) from MM patients have lower miR29b and higher DNMT3B (mRNA and protein) than do cells from patients with monoclonal gammopathy of undetermined significance. Finally, in MM patients, high DNMT3B levels associate with shorter overall survival.

Conclusions

Altogether, this study describes a novel molecular pathway in MM. This pathway starts from CD28 expressed on tumor plasma cells and, through the PI3K-miR29b-DNMT3B axis, leads to epigenetic silencing of immunoproteasome subunits, allowing MM plasma cells to elude immunosurveillance. This discovery has implications for the design of innovative miR29b-based therapies for MM.
Systematic analysis of multi-omics data reveals component-specific blood-based biomarkers for Parkinson’s disease
Authors: Tng Teddy J. W. , Wong Barbara Wing Yan , Sim Esther H. Y. , Tan Eng King , Goh Wilson W. B. , Lim Kah-Leong
Published: April 2024

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder affecting millions of elderly individuals worldwide. Clinically, PD is diagnosed based on the presentation of motoric symptoms. Other methods such as F-DOPA PET scan or α-Synuclein detection from the cerebral spinal fluid are either too expensive or invasive for routine use. Omics platforms such as transcriptomics, proteomics, and metabolomics may identify PD biomarkers from blood, which can reduce cost and increase efficiency. However, there are many biological moieties being measured and issues with false positives/negatives. It is also unknown which omics platform offers most useful information. Therefore, it is important to assess the reliability of these omics studies. Here, we shortlisted and analysed nearly 80 published reports across transcriptomics, proteomics and metabolomics in search of overlapping blood-based biomarkers for PD. The top biomarkers were reported across 29%, 42% and 12.5% of shortlisted papers in transcriptomics, proteomics and metabolomics respectively. These percentages increased to 42%, 60% and 50% accordingly when studies were grouped by specific blood subtypes for analysis, demonstrating the need for test kits to be blood-subtype specific. Following systematic analyses, we propose six novel PD biomarkers: two mRNAs (Whole blood, WB) – Arg1 and SNCA, two proteins (Plasma EV) – SNCA and APOA1, and two metabolites (WB) – 8-OHdG and uric acid for further validation. While these proposed biomarkers are useful, they are also snapshots, representing subsets of larger pathways of origin where the different omics levels corroborate. Indeed, identifying the interconnections across different biological layers can strengthen contextual reasoning, which in turn, would give rise to better quality biomarkers. Knowledge integration across the omics spectrum revealed consistent aberrations on the same neuroinflammation pathway, showcasing the value of integrative (i)-omics agreements for increasing confidence of biomarker selection. We believe that our findings could pave the way for identifying reproducible PD biomarkers, with potential for clinical deployment.

Graphical Abstract

Six Proposed blood-based biomarkers. Seventy-nine publications across transcriptomics, proteomics and metabolomics were shortlisted and analysed for reported biomarkers. The proposed biomarkers are SNCA, APOA1, Arg1, 8-OHdG and Uric acid.
The impact of face coverings on audio-visual contributions to communication with conversational speech
Authors: Jackson I. R. , Perugia E. , Stone M. A. , Saunders G. H.
Published: April 2024

The use of face coverings can make communication more difficult by removing access to visual cues as well as affecting the physical transmission of speech sounds. This study aimed to assess the independent and combined contributions of visual and auditory cues to impaired communication when using face coverings. In an online task, 150 participants rated videos of natural conversation along three dimensions: (1) how much they could follow, (2) how much effort was required, and (3) the clarity of the speech. Visual and audio variables were independently manipulated in each video, so that the same video could be presented with or without a superimposed surgical-style mask, accompanied by one of four audio conditions (either unfiltered audio, or audio-filtered to simulate the attenuation associated with a surgical mask, an FFP3 mask, or a visor). Hypotheses and analyses were pre-registered. Both the audio and visual variables had a statistically significant negative impact across all three dimensions. Whether or not talkers’ faces were visible made the largest contribution to participants’ ratings. The study identifies a degree of attenuation whose negative effects can be overcome by the restoration of visual cues. The significant effects observed in this nominally low-demand task (speech in quiet) highlight the importance of the visual and audio cues in everyday life and that their consideration should be included in future face mask designs.
Desirable and realistic futures of the university: a mixed-methods study with teachers in Denmark
Authors: Pischetola Magda , Stenalt Maria Hvid , Nøhr Liv , Hagood Danielle Elizabeth , Misfeldt Morten
Published: April 2024

In this paper, we put in dialogue the local dimension of a nation-state with the global challenges faced by universities worldwide. We focus on the case of Denmark, a nation that was exceptionally active in implementing international university reforms and where digitalisation is a high priority of the public sector governance. The article seeks to contribute to speculative research and critical studies by presenting a mixed-methods study that explores higher education teachers’ views about desirable and realistic future scenarios in Denmark. The study draws on data from a survey applied at a large Danish university, analysed both quantitatively (N = 755) and qualitatively (N = 53). The findings show that teachers share clusters of concern about uncontrolled digitalisation and teaching automation, commodification of education, and modularisation of university courses, the latter being a contested but realistic perspective in the latest political reforms. They reaffirm the mission of the university as preparing students for solving real problems and contributing to the challenges of the present time. The paper concludes with a call for university management to recalibrate future imaginaries to the values expressed by the teachers, and the university they wish to create.
Biological control potential of two Beauveria bassiana isolates against the stink bugs Nezara viridula L. and Piezodorus guildinii Westwood (Hemiptera: Pentatomidae) in common bean
Authors: Ramos Yordanys , Portal Orelvis , Meyling Nicolai V. , Klingen Ingeborg
Published: April 2024

Background

The stink bugs, Nezara viridula L. and Piezodorus guildinii Westwood (Hemiptera: Pentatomidae) are the most important and widespread species of polyphagous stink bugs in the tropical and subtropical regions of Latin America, which affect the quality and yield of the common bean (Phaseolus vulgaris L.). The use of synthetic chemical insecticides is the major control strategy to manage stink bugs in common beans and alternatives are needed. In this study, mortality and median Lethal Time (LT50) of two Cuban isolates of the entomopathogenic fungus Beauveria bassiana (18 S-O-R and 96 P-O-E), as well as one commercial Cuban isolate (Bb-18), at a concentration of 1 × 108 conidia/ml were evaluated. These evaluations were conducted against both stink bug species using Petri dish bioassays and a semi-field experiment in common beans.

Results

In Petri dish bioassays, the isolates 18 S-O-R and 96 P-O-E caused 100% mortality of both N. viridula and P. guildinii. This was significantly higher than for isolate Bb-18, which caused 86.3% N. viridula and 81.3% P. guildinii mortality. In the semi-field experiment, when pooling both stink bug species, total mortality after 14 days was 91.3% for 18 S-O-R, 80.0% for 96 P-O-E and 73.8% for Bb-18 isolates. LT50 value for isolate 18 S-O-R tested under laboratory conditions was 6.04 ± 0.18 days for N. viridula and 5.32 ± 0.14 days for P. guildinii at the same concentration of 1 × 108 conidia/ml. LT50 value for isolate 18 S-O-R in semi field was 6.79 ± 0.37 days for N. viridula and 7.71 ± 0.32 days for P. guildinii at 1 × 108 conidia/ml.

Conclusion

The study highlights the potential of B. bassiana 18 S-O-R as a promising candidate for control of stink bugs in common bean under tropical conditions as an alternative to conventional chemical insecticides in integrated pest management (IPM) programs. Moving forward, further research should focus on validating the efficacy under diverse field conditions and integrating application methods into practical IPM approaches. Future use of B. bassiana will enhance sustainability and reduce environmental impacts associated with pesticide use.
PeNAC67-PeKAN2-PeSCL23 and B-class MADS-box transcription factors synergistically regulate the specialization process from petal to lip in Phalaenopsis equestris
Authors: Xu Qingyu , Yang Zhenyu , Jia Yupeng , Wang Rui , Zhang Qiyu , Gai Ruonan , Wu Yiding , Yang Qingyong , He Guoren , Wu Ju Hua , Ming Feng
Published: April 2024

The molecular basis of orchid flower development involves a specific regulatory program in which MADS-box transcription factors play a central role. The recent ‘perianth code’ model hypothesizes that two types of higher-order heterotetrameric complexes, namely SP complex and L complex, play pivotal roles in the orchid perianth organ formation. Therefore, we explored their roles and searched for other components of the regulatory network.

Through the combined analysis for transposase-accessible chromatin with high-throughput sequencing and RNA sequencing of the lip-like petal and lip from Phalaenopsis equestris var.trilip, transcription factor-(TF) genes involved in lip development were revealed. PeNAC67 encoding a NAC-type TF and PeSCL23 encoding a GRAS-type TF were differentially expressed between the lip-like petal and the lip. PeNAC67 interacted with and stabilized PeMADS3, which positively regulated the development of lip-like petal to lip. PeSCL23 and PeNAC67 competitively bound with PeKAN2 and positively regulated the development of lip-like petal to petal by affecting the level of PeMADS3. PeKAN2 as an important TF that interacts with PeMADS3 and PeMADS9 can promote lip development. These results extend the ‘perianth code’ model and shed light on the complex regulation of orchid flower development.
Approach to the Patient: Concept and Application of Targeted Radiotherapy in the Paraganglioma Patient
Authors: Pacak Karel , Taieb David , Lin Frank I , Jha Abhishek
Published: April 2024

Paragangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians’ knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. Perspectives in radiotherapies of paraganglioma patients are outlined since they hold promising approaches in the near future that can improve patient outcomes.
Adrenocortical Adenoma With Protrusion Into the Inferior Vena Cava Initially Suspected to Be Adrenocortical Carcinoma
Authors: Takizawa Hiroki , Higuchi Reo , Fukumura Yuki , Terasawa Muga , Sano Katsuhiro , Goto Hiromasa
Published: April 2024

Adrenal tumors with invasion into the inferior vena cava (IVC) are typically malignant. Here, we present a case of adrenocortical adenoma with protrusion into the IVC. A 70-year-old man was referred to our hospital after his magnetic resonance imaging scan of the abdomen coincidently revealed a right adrenal tumor invading the IVC. We suspected an aggressive adrenal carcinoma and tumor resection was performed. However, all 3 existing pathological criteria (Weiss, modified Weiss, and Helsinki) suggested the tumor was benign. Immunohistochemistry for CD31 showed the tumor inside the central adrenal vein (CAV), right adrenal vein (RAV), and IVC was entirely covered with CD31-positive vascular endothelial cells. The CAV is known to sometimes lack smooth muscle in its walls and normal adrenocortical cells covered by endothelial cells sometimes protrude into the CAV from this gap. These findings suggest that this tumor likely protruded into the IVC by pushing against the CAV wall, rather than by invasion into the vascular wall. In the case with adrenal tumors protruding into the IVC, the fact that the tumor surface was covered by vascular endothelial cells was considered supportive of its benign nature.