bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer screening programs in South-east Asia and Western Pacific
Authors: Wee Hwee-Lin , Canfell Karen , Chiu Han-Mo , Choi Kui Son , Cox Brian , Bhoo-Pathy Nirmala , Simms Kate T , Hamashima Chisato , Shen Qianyu , Chua Brandon , Siwaporn Niyomsri , Toes-Zoutendijk Esther
Published: January 2024

Background

The burden of cancer can be altered by screening. The field of cancer screening is constantly evolving; from the initiation of program for new cancer types as well as exploring innovative screening strategies (e.g. new screening tests). The aim of this study was to perform a landscape analysis of existing cancer screening programs in South-East Asia and the Western Pacific.

Methods

We conducted an overview of cancer screening in the region with the goal of summarizing current designs of cancer screening programs. First, a selective narrative literature review was used as an exploration to identify countries with organized screening programs. Second, representatives of each country with an organized program were approached and asked to provide relevant information on the organizations of their national or regional cancer screening program.

Results

There was wide variation in the screening strategies offered in the considered region with only eight programs identified as having an organized design. The majority of these programs did not meet all the essential criteria for being organized screening. The greatest variation was observed in the starting and stopping ages.

Conclusions

Essential criteria of organized screening are missed. Improving organization is crucial to ensure that the beneficial effects of screening are achieved in the long-term. It is strongly recommended to consider a regional cancer screening network.
Physiotherapy-led, community-based airway clearance services for people with chronic lung conditions: a retrospective descriptive evaluation of an existing model of care
Authors: Cooper Laura , Johnston Kylie , Williams Marie
Published: January 2024

Objectives

Airway clearance interventions are recommended for people with chronic lung conditions and mucus hypersecretion, but there are few published models of care or descriptions of airway clearance service provision. This evaluation describes a dedicated, physiotherapy-led, community-based airway clearance service in a metropolitan local health network.

Design

Retrospective evaluation using existing airway clearance service administrative database.

Participants

All first referrals to the airway clearance service in a 5-year period (1/1/2017 to 31/12/2021).

Main outcome measures

Available service data grouped into four domains: participant demographics, referral demographics, service provision and outcomes.

Results

Of the 1335 first referrals eligible for inclusion, 1157 (87%) people attended. Bronchiectasis was the commonest condition (n = 649/1135, 49%). A total of 2996 occasions of service (face to face clinic n = 2108, 70%, phone n = 736, 25%, telehealth n = 99, 3%, home visit n = 53, 2%) were delivered. Airway clearance devices frequently prescribed were the Aerobika (525/1157, 45%), bubble-positive expiratory pressure (263/1157, 23%) and the Acapella (127/1157, 11%). On average, initial appointment with the airway clearance service occurred within 36 days of referral and people attended the service three times. Individuals voluntarily completed both pre/post service questionnaires around a third of the time. At least half of responders reported an improvement in respiratory symptom outcome measures consistent with the minimum clinically important difference.

Conclusions

This evaluation describes an airway clearance service as it exists, providing an example from which airway clearance services can be planned, implemented and improved.
Proteomic associations with forced expiratory volume: a Mendelian randomisation study
Authors: Axelsson Gisli Thor , Jonmundsson Thorarinn , Woo Youngjae , Frick Elisabet Alexandra , Aspelund Thor , Loureiro Joseph J. , Orth Anthony P. , Jennings Lori L. , Gudmundsson Gunnar , Emilsson Valur , Gudmundsdottir Valborg , Gudnason Vilmundur
Published: January 2024

Background

A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1.

Methods

Data from the population-based AGES-Reykjavik study were used. Serum proteomic measurements were done using 4782 DNA aptamers (SOMAmers). Data from 1479 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional two-sample Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102).

Results

In observational analyses, 530 SOMAmers were associated with FEV1 after multiple testing adjustment (FDR < 0.05). The most significant were Retinoic Acid Receptor Responder 2 (RARRES2), R-Spondin 4 (RSPO4) and Alkaline Phosphatase, Placental Like 2 (ALPPL2). Of the 257 SOMAmers with genetic instruments available, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta (ERO1B) and Apolipoprotein M (APOM). THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments.

Conclusions

In summary, this large scale proteogenomic analyses of FEV1 reveals circulating protein markers of FEV1, as well as several proteins with potential causality to lung function.
Unraveling EGFR-TKI resistance in lung cancer with high PD-L1 or TMB in EGFR-sensitive mutations
Authors: Ding Wuwu , Yang Pengmin , Zhao Xiaokai , Wang Xiaozhi , Liu Huaqing , Su Qing , Wang Xintao , Li Jieyi , Gong Ziying , Zhang Daoyun , Wang Xinwei
Published: January 2024

Background

Although EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) have been extensively studied, certain patient subgroups remain with unclear mechanisms. This retrospective study analysed mutation data of NSCLC patients with EGFR-sensitive mutations and high programmed death-ligand 1 (PD-L1) expression or high TMB to identify primary resistance mechanisms.

Methods

Hybrid capture-based next-generation sequencing (NGS) was used to analyse mutations in 639 genes in tumor tissues and blood samples from 339 NSCLC patients. PD-L1 immunohistochemical staining was also performed on the same cell blocks. Molecular and pathway profiles were compared among patient subgroups.

Results

TMB was significantly higher in lung cancer patients with EGFR-sensitive mutations and high PD-L1 expression. Compared with the high-expression PD-L1 or high TMB and low-expression or TMB groups, the top 10 genes exhibited differences in both gene types and mutation rates. Pathway analysis revealed a significant mutations of the PI3K signaling pathway in the EGFR-sensitive mutation group with high PD-L1 expression (38% versus 12%, p < 0.001) and high TMB group (31% versus 13%, p < 0.05). Notably, PIK3CA and PTEN mutations emerged as the most important differentially mutated genes within the PI3K signaling pathway.

Conclusions

Our findings reveal that the presence of PI3K signaling pathway mutations may be responsible for inducing primary resistance to EGFR-TKIs in NSCLC patients with EGFR-sensitive mutations along with high PD-L1 expression or high TMB. This finding is of great significance in guiding subsequent precision treatments in NSCLC.
Phenotypic subtypes of fibrotic hypersensitivity pneumonitis identified by machine learning consensus clustering analysis
Authors: Petnak Tananchai , Cheungpasitporn Wisit , Thongprayoon Charat , Sodsri Tulaton , Tangpanithandee Supawit , Moua Teng
Published: January 2024

Background

Patients with fibrotic hypersensitivity pneumonitis (f-HP) have varied clinical and radiologic presentations whose associated phenotypic outcomes have not been previously described. We conducted a study to evaluate mortality and lung transplant (LT) outcomes among clinical clusters of f-HP as characterized by an unsupervised machine learning approach.

Methods

Consensus cluster analysis was performed on a retrospective cohort of f-HP patients diagnosed according to recent international guideline. Demographics, antigen exposure, radiologic, histopathologic, and pulmonary function findings along with comorbidities were included in the cluster analysis. Cox proportional-hazards regression was used to assess mortality or LT risk as a combined outcome for each cluster.

Results

Three distinct clusters were identified among 336 f-HP patients. Cluster 1 (n = 158, 47%) was characterized by mild restriction on pulmonary function testing (PFT). Cluster 2 (n = 46, 14%) was characterized by younger age, lower BMI, and a higher proportion of identifiable causative antigens with baseline obstructive physiology. Cluster 3 (n = 132, 39%) was characterized by moderate to severe restriction. When compared to cluster 1, mortality or LT risk was lower in cluster 2 (hazard ratio (HR) of 0.42; 95% CI, 0.21–0.82; P = 0.01) and higher in cluster 3 (HR of 1.76; 95% CI, 1.24–2.48; P = 0.001).

Conclusions

Three distinct phenotypes of f-HP with unique mortality or transplant outcomes were found using unsupervised cluster analysis, highlighting improved mortality in fibrotic patients with obstructive physiology and identifiable antigens.
‘Mother(Nature) knows best’ – hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database
Authors: Gorczyca Maria , Białas Wojciech , Nicaud Jean-Marc , Celińska Ewelina
Published: January 2024

Background

In the era of rationally designed synthetic biology, heterologous metabolites production, and other counter-nature engineering of cellular metabolism, we took a step back and recalled that ‘Mother(-Nature) knows best’. While still aiming at synthetic, non-natural outcomes of generating an ‘over-production phenotype’ we dug into the pre-designed transcriptional programs evolved in our host organism—Yarrowia lipolytica, hoping that some of these fine-tuned orchestrated programs could be hijacked and used. Having an interest in the practical outcomes of the research, we targeted industrially-relevant functionalities—stress resistance and enhanced synthesis of proteins, and gauged them over extensive experimental design’s completion.

Results

Technically, the problem was addressed by screening a broad library of over 120 Y. lipolytica strains under 72 combinations of variables through a carefully pre-optimized high-throughput cultivation protocol, which enabled actual phenotype development. The abundance of the transcription program elicitors—transcription factors (TFs), was secured by their overexpression, while challenging the strains with the multitude of conditions was inflicted to impact their activation stratus. The data were subjected to mathematical modeling to increase their informativeness.

The amount of the gathered data prompted us to present them in the form of a searchable catalog – the YaliFunTome database (https://sparrow.up.poznan.pl/tsdatabase/)—to facilitate the withdrawal of biological sense from numerical data. We succeeded in the identification of TFs that act as omni-boosters of protein synthesis, enhance resistance to limited oxygen availability, and improve protein synthesis capacity under inorganic nitrogen provision.

Conclusions

All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest.
Osteoking promotes bone formation and bone defect repair through ZBP1–STAT1–PKR–MLKL-mediated necroptosis
Authors: Zhang Suya , Liu Yudong , Ma Zhaochen , Gao Shuangrong , Chen Lin , Zhong Honggang , Zhang Chu , Li Tao , Chen Weiheng , Zhang Yanqiong , Lin Na
Published: January 2024

Background

Osteoking has been used for fracture therapy with a satisfying clinical efficacy. However, its therapeutic properties and the underlying mechanisms remain elusive.

Method

A bone defect rat model was established to evaluate the pharmacological effects of Osteoking by the dynamic observation of X-ray, micro-CT and histopathologic examination. Transcriptome profiling was performed to identify bone defect-related genes and Osteoking effective targets. Then, a “disease-related gene–drug target” interaction network was constructed and a list of key network targets were screened, which were experimentally verified.

Results

Osteoking effectively promoted bone defect repair in rats by accelerating the repair of cortical bone and the growth of trabeculae. Histopathologically, the bone defect rats displayed lower histopathologic scores in cortical bone, cancellous bone and bone connection than normal controls. In contrast, Osteoking exerted a favorable effect with a dose-dependent manner. The abnormal serum levels of bone turnover markers, bone growth factors and bone metabolism-related biochemical indexes in bone defect rats were also reversed by Osteoking treatment. Following the transcriptome-based network investigation, we hypothesized that osteoking might attenuate the levels of ZBP1–STAT1–PKR–MLKL-mediated necroptosis involved into bone defect. Experimentally, the expression levels of ZBP1, STAT1, PKR and the hallmark inflammatory cytokines for the end of necroptosis were distinctly elevated in bone defect rats, but were all effectively reversed by Osteoking treatment, which were also suppressed the activities of RIPK1, RIPK3 and MLKL in bone tissue supernatants.

Conclusions

Osteoking may promote bone formation and bone defect repair by regulating ZBP1–STAT1–PKR axis, leading to inhibit RIPK1/RIPK3/MLKL activation-mediated necroptosis.
Factors affecting the ability of patients with complex vascular anomalies to navigate the healthcare system
Authors: Sisk Bryan , Lin Sunny , Kerr Anna M.
Published: January 2024

Background

Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients’ ability to navigate the healthcare system.

Results

We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the “Navigating the Healthcare System” subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the healthcare system using multivariate linear regression (n = 136). We also performed an exploratory model that included the primary care doctor’s knowledge of VAs for the subset of participants with a primary care doctor (n = 114). Participants were predominantly women (n = 90, 66%), White and non-Hispanic (n = 109, 73%), and college-educated (n = 101, 73%). Most participants had PIK3CA-Related Overgrowth Spectrum (n = 107, 78%). Most participants reported that navigating the healthcare system was “sometimes” or “usually difficult” (mean score 16.4/30, standard deviation 5.6). In multivariate linear regression, ability to navigate the healthcare system was associated positively with quality of information exchange (β = 0.38, 95% Confidence Interval (CI) 0.22 to 0.55, p <.001) and whether patients had VA specialists (β = 2.31, 95% CI 0.35 to 4.28, p =.021), but not associated with patient self-advocacy, anxiety, education, age, race and ethnicity, gender, or having a primary care doctor. In exploratory analysis of participants with primary care doctors, ability to navigate the healthcare system was positively associated with quality of information exchange (β = 0.27, 95% CI 0.09 to 0.45, p =.004), having a VA specialist (β = 2.31, 95% CI 0.22 to 4.39, p =.031), and primary care doctors’ VA knowledge (β = 0.27, 95% CI 0.04 to 0.50, p =.023).

Conclusion

Patients with VAs struggle to navigate the healthcare system. High-quality information from clinicians and more knowledgeable primary care doctors might help patients to access needed care. Relying on patient self-advocacy is insufficient. Future efforts should focus on patient-directed and clinician-directed educational interventions. Additionally, future work should assess the structural barriers that impede healthcare access for these patients.
The reliability and quality of YouTube videos as a source of breath holding spell
Authors: Demirtas Mehmet Semih , Alici Nurettin
Published: January 2024

Background

Breath holding spells (BHS) are an important non-epileptic condition that is common in childhood and causes concern to families. YouTube is a powerful social media tool for accessing diseases and information such as BHS in child health. The aim of the study was to measure of the quality and reliability levels of the videos published in English on BHS uploaded on YouTube.

Methods

The key words “infant”, “cry”, “breath holding spells”, holding spells” and “breath spells” were searched on the YouTube on November 14, 2022, in this study. Along with the general features of the videos, their quality and reliability were evaluated according to the global quality score (GQS), mDISCERN score.

Results

Fifty-five videos were evaluated. The mDISCERN and GQS scores of the videos in the useful group were higher than those in the misleading group (p < 0.001, p < 0.001). In the useful group, 87.5% of academic institutions and 93.3% of medical doctors (MDs) uploaded high-score GQS videos, while this rate was 16.7% in independent users (p = 0.005). The positive correlation was found between mDISCERN and GQS scores (p < 0.001).

Conclusion

The majority of YouTube videos on BHS contained useful information with sufficient quality. Professional associations such as universities and academic institutes need to produce better quality videos to provide families/users with more accurate and up-to-date information about BHS. We emphasize that YouTube should analyse videos published in the field of health, especially in the field of pediatrics, such as BHS, with committees consisting of expert health professionals, and publish them after evaluation. YouTube should consider collaborating with professional pediatrics health organizations such as American Academy of Pediatrics (AAP), academic institutes and universities in the field of BHS to produce high-quality videos.
The prevention of rectovaginal fistula after rectal cancer surgery by packing with laparoscopic dislocated fat flap containing ovarian vascular pedicle anterior to the anastomotic stoma: a parallel group randomized controlled trial protocol
Authors: Ye Dao-xiong , Huang Sheng-hui , Lin Yu , Ying-Huang  , Chi Pan
Published: January 2024

Background

Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation.

Methods

In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10–15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. Control group: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF.

Discussion

This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF.

Trial registration

Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol.
Association of biochemical markers with bone marrow lesion changes on imaging—data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium
Authors: Yu Shirley P. , Deveza Leticia A. , Kraus Virginia B. , Karsdal Morten , Bay-Jensen Anne-Christine , Collins Jamie E. , Guermazi Ali , Roemer Frank W. , Ladel Christoph , Bhagavath Venkatesha , Hunter David J.
Published: January 2024

Background

To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI.

Methods

Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0–3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iβ, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined.

Results

Increases in serum CTX-I and urinary CTX-Iβ over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline.

Conclusions

Short-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iβ hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.
Does video assistant referee technology change the magnitude and direction of home advantages and referee bias? A proof-of-concept study
Authors: Işın Ali , Yi Qing
Published: January 2024

Background

This study analyzed how Video Assistant Referee (VAR), introduced to improve the accuracy of referee decisions in football, changes the magnitude and direction of home advantage and referee bias in the Turkish Super League.

Methods

We analyzed points, goals, yellow cards and red cards, fouls, penalties, and offside data from 1,838 matches played in the Turkish Super League with and without VAR. Two-sample t-tests and two one-sided tests analysis were applied to determine the differences between the home and away team data between the seasons played with and without VAR.

Results

The findings revealed that the only variable that changed significantly after VAR was implemented was fouls, which decreased for both home (p <.001; d = 0.56, medium effect) and away teams (p <.001; d = 0.69, medium effect). The results also indicated that, with or without VAR, home teams had an advantage over away teams in points and goals, and away teams faced more referee bias regarding yellow cards and penalties (against).

Conclusions

Although this study shows that VAR does not significantly impact the HA and referee bias of football matches, nevertheless, teams should be more aware that bias is reduced when playing away. In addition, this study offers some practical applications that can help football players, coaches, and match officials better understand VAR technology’s effects on HA and referee bias.
Comparison of immediate versus optional delayed surgical repair for treatment of acute anterior cruciate ligament injury through a parallel, multicentric, pragmatic randomized controlled trial – IODA trial
Authors: Smeets Annemie , Ghafelzadeh Ahwaz Feryal , Bogaerts Stijn , Berger Pieter , Peers Koen
Published: January 2024

Background

Standard care for anterior cruciate ligament (ACL) injuries often includes surgical reconstruction of the ACL. However, two randomized controlled trials [1, 2] (RCT) concluded that conservative treatment does not result in inferior clinical outcomes compared to immediate ACL reconstruction. More research is needed to verify these results and assess whether patient-specific parameters determine if a patient would benefit from one treatment option over the other.

Methods

This is a pragmatic, multi-center RCT with two parallel groups. Patients with an acute ACL injury will be recruited from Belgian hospitals. Patients will be randomized to conservative treatment (rehabilitation + optional delayed surgery) or immediate ACL reconstruction (< 12 weeks). The primary outcome is the Knee injury and Osteoarthritis Outcome Score (KOOS) at 7 months (short term) and 1-year long term) post-injury. These following additional outcomes will be administered at 4 and 7 months (short term) and 1, 2, and 3 years post-injury (long term): patient-reported outcomes concerning knee symptoms, knee function and quality of life, functional knee tests, time to return to pre-injury activity level and return to work, structural knee joint damage and cartilage health (only at 4 months and 3 years post-injury), as well as adverse events such as re-rupture rates. Furthermore, the secondary objective is to identify (through a predictive analysis) individuals who would benefit the most from early reconstruction versus those who should rather be treated conservatively.

Discussion

This large RCT will assess the clinical effectiveness of both surgical and conservative treatment. In addition, it will be the first study that provides insights into which patient-specific factors predict successful outcomes after conservative treatment of ACL injuries. These results will be the first step toward early patient identification regarding treatment decisions. This is urgently needed to avoid (1) delayed surgeries and prolonged rehabilitation and (2) unnecessary surgeries.

Trial registration

this trial was registered on ClinicalTrials.gov (NCT05747079) on 10/02/2023.
A single-domain antibody detects and neutralises toxic Aβ42 oligomers in the Alzheimer’s disease CSF
Authors: Bigi Alessandra , Napolitano Liliana , Vadukul Devkee M. , Chiti Fabrizio , Cecchi Cristina , Aprile Francesco A. , Cascella Roberta
Published: January 2024

Background

Amyloid-β42 (Aβ42) aggregation consists of a complex chain of nucleation events producing soluble oligomeric intermediates, which are considered the major neurotoxic agents in Alzheimer’s disease (AD). Cerebral lesions in the brain of AD patients start to develop 20 years before symptom onset; however, no preventive strategies, effective treatments, or specific and sensitive diagnostic tests to identify people with early-stage AD are currently available. In addition, the isolation and characterisation of neurotoxic Aβ42 oligomers are particularly difficult because of their transient and heterogeneous nature. To overcome this challenge, a rationally designed method generated a single-domain antibody (sdAb), named DesAb-O, targeting Aβ42 oligomers.

Methods

We investigated the ability of DesAb-O to selectively detect preformed Aβ42 oligomers both in vitro and in cultured neuronal cells, by using dot-blot, ELISA immunoassay and super-resolution STED microscopy, and to counteract the toxicity induced by the oligomers, monitoring their interaction with neuronal membrane and the resulting mitochondrial impairment. We then applied this approach to CSF samples (CSFs) from AD patients as compared to age-matched control subjects.

Results

DesAb-O was found to selectively detect synthetic Aβ42 oligomers both in vitro and in cultured cells, and to neutralise their associated neuronal dysfunction. DesAb-O can also identify Aβ42 oligomers present in the CSFs of AD patients with respect to healthy individuals, and completely prevent cell dysfunction induced by the administration of CSFs to neuronal cells.

Conclusions

Taken together, our data indicate a promising method for the improvement of an early diagnosis of AD and for the generation of novel therapeutic approaches based on sdAbs for the treatment of AD and other devastating neurodegenerative conditions.
Associations of cerebrospinal fluid complement proteins with Alzheimer’s pathology, cognition, and brain structure in non-dementia elderly
Authors: Li Meng , Ma Ya-Hui , Guo Yun , Liu Jia-Yao , Tan Lan ,   on behalf of Alzheimer’s Disease Neuroimaging Initiative
Published: January 2024

Background

Cerebrospinal fluid (CSF) complement activation is a key part of neuroinflammation that occurs in the early stages of Alzheimer’s disease (AD). However, the associations of CSF complement proteins with AD pathology, cognition, and structural neuroimaging biomarkers for AD have been rarely investigated.

Methods

A total of 210 participants (125 mild cognitive impairment [MCI] patients and 85 normal controls) were included from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who measured AD pathology, cognition, and neuroimaging at baseline and every 12 months. The mixed-effect linear models were utilized to investigate longitudinal associations of CSF complement proteins with AD pathology, cognition, and neuroimaging in cognitively normal (CN) and mild cognitive impairment (MCI) subjects. Causal mediation analyses were conducted to explore the potential mediators between CSF complement proteins and cognitive changes.

Results

We found that the subjects with low CSF complement protein levels at baseline had worse outcomes in AD pathology, indicated by their lowest concentrations observed in A + and A + T + individuals. The reduced CSF complement proteins were associated with faster accumulation of tau among CN subjects and with cognitive decline and greater brain atrophy of specific regions among MCI subjects. Furthermore, mediation analyses showed that the effects of CSF complement proteins on cognitive performance were partially mediated by regional brain structures (mediation proportions range from 19.78 to 94.92%; p < 0.05).

Conclusions

This study demonstrated that CSF complement proteins were involved in the early progression of AD. Our results indicated that regional brain atrophy might be a plausible way to connect CSF complement protein levels and cognition.
The buffet challenge: a behavioral assessment of eating behavior in adolescents with an eating disorder
Authors: Cooper Marita , Mears Connor , Heckert Kerri , Orloff Natalia , Peebles Rebecka , Timko C. Alix
Published: January 2024

Objective

Eating disorders are characterized by disturbances in nutritional intake and abnormal mealtime behaviors. Laboratory eating paradigms offer a unique opportunity to accurately measure dietary intake and eating behaviors, however, these studies have predominantly occurred in adults. This paper describes the development and preliminary psychometric examination of the Buffet Challenge, a laboratory-based meal task for youths with an eating disorder.

Method

We recruited and assessed 56 participants as part of a randomized controlled trial of Family-Based Treatment for adolescents with anorexia nervosa. Adolescents completed the Buffet Challenge at baseline, midway through treatment (~ week 16 of a 6 months course), and end of treatment. Participants and their parents also reported eating disorder symptomatology and treatment related variables of interest were recorded.

Results

All adolescents were willing to complete the Buffet Challenge at all time points, although one refused to give up their cellphone, and there were no significant adverse events recorded. Preliminary results are presented.

Conclusions

Our initial pilot of this task in adolescents with anorexia nervosa demonstrates its acceptability, although investigation of our hypotheses was hindered by significant missing data due to COVID-related research shutdowns. Future studies should replicate procedures in a larger sample to ensure analyses are adequately powered.
A simplified measure of burnout symptoms among paramedics - an exploratory analysis of a Hungarian sample
Authors: Ivánkovits László , Kazinczi Csaba , Kocsis Krisztián , Stankovic Mona , Koday Zsuzsanna , Pető Zoltán , Töreki Annamária
Published: January 2024

Background

Burnout is still one of the leading mental health problems. According to research results over the past decades, healthcare workers, including paramedics, are considered a high-risk group. In concordance with these results, the available resources need to prioritize monitoring paramedics’ mental health.

Methods

In our study, we investigated whether the available test batteries measuring burnout could be reduced while maintaining their effectiveness. We reduced the 21-item Burnout Measurement and the 8-item version of the Psychosomatic Symptom Scale using the data of 727 Hungarian paramedics. We selected the top four items of the questionnaires that were significantly correlated with the original Burnout Measure Index and the Psychosomatic Scale Index. The classification efficiency of the shortened list of items was based on the initial risk categories of the Burnout Measure and its sensitivity was analyzed using Binary Logistic regression and ROC curves. We then used Two-Step Cluster Analysis to test the ability of the shortened Burnout Measure Index to develop new risk categories. The reliability indicators were also explored.

Results

The results show that the Burnout Measurement can be reduced to 4 items with a classification efficiency of 93.5% in determining the level of burnout. The 5-item reduction of the Psychosomatic Symptom Scale can classify subjects to the appropriate intervention level for burnout with an efficiency of 81.6%. The ROC analysis suggests that the shortened questionnaires have an excellent separative ability to discriminate between the initial risk groups. Three new risk categories were also identified as a result of the cluster analysis.

Conclusion

The shortened scales may be proven effective in resource management, which could significantly quicken the assessment of burnout in the future. The abbreviated scale is also suitable for classifying subjects into risk categories. However, further research is needed to see whether the shortened scales can be used as a diagnostic tool.
The interrelationships between Chinese learners’ trait emotional intelligence and teachers’ emotional support in learners’ engagement
Authors: Yan Yao , Zhang Xusheng , Lei Tong , Zheng Pei , Jiang Chao
Published: January 2024

Background

One noteworthy concern within the realm of education is the level of engagement demonstrated by students. Among the factor that can have a crucial role in this domain is teacher support, especially emotional support which has an impact on several aspects of learners’ education. Furthermore, various studies have investigated the relationship between Emotional Intelligence (EI) and learners’ engagement.

Methods

Accordingly, this study investigated the possible role of trait EI and the emotional support of teachers and how these constructs may work to associate learners’ engagement. For this objective, a total of 309 Chinese students across different colleges and universities in 5 provinces of Beijing, Shanghai, Jiangsu, Hubei, and Shaanxi were enrolled. They were 126 females and 183 males, with ages ranging from 18 to 30 years old (Mean = 24.6).

Results

The results of this research through running Structural Equation Modeling (SEM) demonstrated that teachers’ emotional support and trait EI both can associate students’ learning engagement. The final measurement model shows that about 73% of changes in learners’ engagement can be associated by their trait EI and teachers’ emotional support.

Conclusions

This study underscores the importance of emotional support from teachers and the trait of EI in relation to students’ engagement in learning. Both factors were shown to play a significant role in associating student engagement. Moreover, this study could potentially have wider impacts on members of academic teams.
A study protocol testing pre-exposure dose and compound pre-exposure on the mechanisms of latent inhibition of dental fear
Authors: Geers Andrew L. , Seligman Laura D. , Pituch Keenan A. , Colagiuri Ben , Marusak Hilary A. , Rabinak Christine A. , Turner Natalie , Al-Ado Sena L. , Nedley Michael
Published: January 2024

Background

Dental stimuli can evoke fear after being paired - or conditioned - with aversive outcomes (e.g., pain). Pre-exposing the stimuli before conditioning can impair dental fear learning via a phenomenon known as latent inhibition. Theory suggests changes in expected relevance and attention are two mechanisms responsible for latent inhibition. In the proposed research, we test whether pre-exposure dose and degree of pre-exposure novelty potentiate changes in expected relevance and attention to a pre-exposed stimulus. We also assess if the manipulations alter latent inhibition and explore the possible moderating role of individual differences in pain sensitivity.

Methods

Participants will be healthy individuals across a wide range of ages (6 to 35 years), from two study sites. Participants will undergo pre-exposure and conditioning followed by both a short-term and long-term test of learning, all in a novel virtual reality environment. The unconditioned stimulus will be a brief pressurized puff of air to a maxillary anterior tooth. Pre-exposure dose (low vs. high) and pre-exposure novelty (element stimulus vs. compound stimuli) will be between-subject factors, with stimulus type (pre-exposed to-be conditioned stimulus, a non-pre-exposed conditioned stimulus, and an unpaired control stimulus) and trial as within-subject factors. Pain sensitivity will be measured through self-report and a cold pressor test. It is hypothesized that a larger dose of pre-exposure and compound pre-exposure will potentiate the engagement of the target mechanisms and thereby result in greater latent inhibition in the form of reduced fear learning. Further, it is hypothesized that larger effects will be observed in participants with greater baseline pain sensitivity.

Discussion

The proposed study will test whether pre-exposure dose and compound stimulus presentation change expected relevance and attention to the pre-exposed stimulus, and thereby enhance latent inhibition of dental fear. If found, the results will add to our theoretical understanding of the latent inhibition of dental fear and inform future interventions for dental phobia prevention.
Non-targeted discovery of high-value bio-products in Nicotiana glauca L: a potential renewable plant feedstock
Authors: Carreno-Quintero Natalia , Tohge Takayuki , Van Acker Rebecca , McKee Lauren S. , Zhou Qi , Bolze Antje , Xing Xiaohui , Özparpucu Merve , Rüggeberg Markus , Piofczyk Thomas , Koram Yaw , Bulone Vincent , Boerjan Wout , Fernie Alisdair R. , Fraser Paul D.
Published: January 2024

The evaluation of plant-based feedstocks is an important aspect of biorefining. Nicotiana glauca is a solanaceous, non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions. In the present article, compatible sequential solvent extractions were applied to N. glauca leaves to enable the generation of enriched extracts containing higher metabolite content comparing to direct leaf extracts. Typically, between 60 to 100 metabolite components were identified within the fractions. The occurrence of plant fatty acids, fatty acid alcohols, alkanes, sterols and terpenoids was detected by gas liquid chromatography–mass spectrometry (GC–MS) and metabolite identification was confirmed by comparison of physico-chemical properties displayed by available authentic standards. Collectively, co-products such waxes, oils, fermentable sugars, and terpenoids were all identified and quantified. The enriched fractions of N. glauca revealed a high level of readily extractable hydrocarbons, oils and high value co-products. In addition, the saccharification yield and cell wall composition analyses in the stems revealed the potential of the residue material as a promising lignocellulosic substrate for the production of fermentable sugars. In conclusion a multifractional cascade for valuable compounds/commodities has been development, that uses N. glauca biomass. These data have enabled the evaluation of N. glauca material as a potential feedstock for biorefining.

Graphical Abstract
Inexpensive short-circuit current limiter and switching device based on one commutation circuit for a three-phase system
Authors: Ahmed A. R. , Hamada Abdallah M. , Hasan Saady , Abdel-Latif K. M.
Published: January 2024

The escalating levels of fault currents resulting from short circuits, particularly in the context of distribution generators, have presented a critical need for the widespread implementation of fault current limiters (FCLs) in power systems. Despite their evident advantages, the extensive adoption of FCLs has been hindered by the high production costs associated with these devices. To address this challenge, a comprehensive study was conducted to develop a cost-effective FCL tailored specifically for three-phase power systems. This paper proposes a novel approach based on a single commutation circuit for the FCL and offers detailed insights into the construction of the FCL circuit, with a particular focus on efficient current interruption. Additionally, the study comprehensively discusses the logic controller and measurement system employed in conjunction with the proposed FCL, ensuring precise fault detection and rapid response to disturbances within the power grid. The integration of an artificial zero-crossing circuit within the FCL design further enhances its capability to limit short-circuit currents proactively, even before the occurrence of the first peak, thereby bolstering overall system reliability and stability. The study's significant contribution lies in achieving cost-effectiveness through the simplicity of the FCL's design, eliminating the need for extensive upgrades to various network components.
A comparative study of short-term phonatory outcomes in primary cases of early glottic cancer treated with radiotherapy versus laser surgery
Authors: Gupta Devender Kumar , Ravunnikutty Mahesh , Singh Sanajeet Kumar , Chugh Rajeev , Roy Ravi , Goyal Sunil , Swami Himanshu , Patel Bhaumik , Yadav Sneha , Banger Sween
Published: January 2024

Background

Early-stage glottic carcinomas can be treated with either laser surgery or radiotherapy. Both approaches have demonstrated similar cure rates. However, the question of which modality is superior in terms of voice outcomes remains a topic of debate.

Methods

In our study, we conducted a comparison of short-term phonatory outcomes in patients with primary early glottic cancer who underwent treatment using both modalities. We assessed these outcomes using videostroboscopy and voice analysis software at three time points: immediately following treatment, at 1 month, and at 3 months post-treatment.

Results

Voice analysis revealed that laser surgery had a more favorable immediate effect compared to radiotherapy in parameters such as jitter, shimmer, harmonics-to-noise ratio, and fundamental frequency. However, at the 3-month post-treatment mark, both treatment modalities demonstrated similar effects. Additionally, both modalities had comparable effects on maximum phonation time. Videostroboscopy observations showed that mucosal wave forms were more prominent immediately after laser surgery and gradually improved following radiotherapy. Furthermore, patients with incomplete glottic closure experienced recovery after both treatment modalities.

Conclusion

Based on the results, there are better outcomes immediately following LS compared to RT. However, after a 3-month period, the outcomes of both treatment modalities become comparable. The treating physicians must consider various factors such as complications, patient-specific considerations, treatment costs, and duration to make informed decisions. A personalized approach considering the individual patient’s circumstances is crucial in achieving optimal results in the management of T1 laryngeal cancer.
Efficient signal-to-noise ratio enhancement model for severely contaminated distributed acoustic sensing seismic data based on heterogeneous knowledge distillation
Authors: Feng Qiankun , Wang Shignag , Li Yue
Published: January 2024

Distributed acoustic sensing (DAS) is an emerging seismic acquisition technique with great practical potential. However, various types of noise seriously corrupt DAS signals, making it difficult to recover signals, particularly in low signal-to-noise ratio (S/N) regions. Existing deep-learning methods address this challenge by augmenting data sets or strengthening the complex architecture, which can cause overdenoising and a computational power burden. Hence, the heterogeneous knowledge distillation (HKD) method is developed to more efficiently address the signal reconstruction under low S/N. HKD uses ResNet 20 as the teacher and student (T-S) model. It uses residual learning and skip connections to facilitate feature representation at deeper levels. The main contribution is the training of the T-S framework with different noise levels. The teacher model that is trained using slightly noisy data serves as a powerful feature extractor to capture more accurate signal features because high-quality data are easy to recover. By minimizing the difference between the outputs of T-S models, the student model that is trained using severely noisy data can distill the absent signal features from the teacher to improve its own signal recovery, which enables heterogeneous feature distillation. Furthermore, simultaneous positive and negative learning (P&NL) is developed to extract more useful features from the teacher, enabling the T-S framework to learn from the predicted signal and noise during training. Consequently, a new loss function that combines student denoising loss and HKD loss weighted by P&NL is developed to alleviate signal leakage. The experimental results demonstrate that the HKD achieves distinct and consistent signal recovery without increasing computational costs.