bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy regimen for III–IVA esophageal squamous cell carcinoma post-surgery
Authors: Li Chunyang , Yu Pengyi , Li Hong , Yang Xin , Wang Jun , Jiang Bo
Published: January 2024

Background and aims

The treatment of esophageal squamous cell carcinoma is still controversial, and neoadjuvant chemotherapy combined with immunotherapy is a hot topic of current research. We investigated the recent efficacy and surgical safety of patients with III–IVA esophageal squamous cell carcinoma after neoadjuvant regimen of paclitaxel + cisplatin/nedaplatin/carboplatin + sindilizumab, to provide a theoretical basis for evaluating the feasibility of surgery after neoadjuvant therapy.

Methods

The clinical data of patients with stage III–IVA esophageal squamous cell carcinoma admitted from January 2022 to April 2023 at our hospital were collected for retrospective analysis. The patients were divided into the neoadjuvant combination surgery group (34 patients with the regimen of paclitaxel + cisplatin/nedaplatin/carboplatin + sintilimab two/three cycles of preoperative neoadjuvant therapy) and surgery-only group (36 patients). Statistical analysis was performed to compare the differences between both groups particularly for intraoperative bleeding, operative time, incidence of postoperative pulmonary complications, laryngeal recurrent nerve injury, thoracic duct injury, anastomotic fistula, and postoperative hospital days. Additionally, the pCR/MPR rates of the neoadjuvant group were analysed.

Results

Significant differences were present in the clinical and pathological staging before and after neoadjuvant treatment (P ≤ 0.001). The neoadjuvant group had a pCR rate of 26.47% and an ORR rate of 88.23%. No significant differences were discovered in R0 resection rate between both groups, as well as intraoperative bleeding, operative time, intraoperative laryngeal recurrent nerve injury rate, thoracic duct injury rate, postoperative anastomosis incidence, postoperative hospital days, and postoperative lung infection incidence (P > 0.05).

Conclusions

The neoadjuvant immune combination chemotherapy regimen had considerable tumor regression and pathological remission benefits, without reducing the safety of surgery, possibly presenting as a new treatment plan.
MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation
Authors: Yu Shanshan , Chen Cheng , Chen Ming , Liang Jinxiao , Jiang Kecheng , Lou Bin , Lu Jun , Zhu Xiaohua , Zhou Donghui
Published: January 2024

Background

Gastric cancer (GC) is associated with high mortality and heterogeneity and poses a great threat to humans. Gene therapies for the receptor tyrosine kinase RON and its spliceosomes are attracting increasing amounts of attention due to their unique characteristics. However, little is known about the mechanism involved in the formation of the RON mRNA alternative spliceosome RONΔ160.

Methods

Fourteen human GC tissue samples and six normal gastric tissue samples were subjected to label-free relative quantitative proteomics analysis, and MAGOH was identified as a candidate protein for subsequent studies. The expression of MAGOH in clinical specimens was verified by quantitative real-time PCR and western blotting. We then determined the biological function of MAGOH in GC through in vitro and in vivo experiments. RNA pulldown, RNA sequencing and RNA immunoprecipitation (RIP) were subsequently conducted to uncover the underlying mechanism by which MAGOH regulated the formation of RONΔ160.

Results

Proteomic analysis revealed that MAGOH, which is located at key nodes and participates in RNA processing and mRNA splicing, was upregulated in GC tissue and GC cell lines and was associated with poor prognosis. Functional analysis showed that MAGOH promoted the proliferation, migration and invasion of GC cells in vitro and in vivo. Mechanistically, MAGOH inhibited the expression of hnRNPA1 and reduced the binding of hnRNPA1 to RON mRNA, thereby promoting the formation of RONΔ160 to activate the PI3K/AKT signaling pathway and consequently facilitating GC progression.

Conclusions

Our study revealed that MAGOH could promote the formation of RONΔ160 and activate the PI3K/AKT signaling pathway through the inhibition of hnRNPA1 expression. We elucidate a novel mechanism and potential therapeutic targets for the growth and metastasis of GC based on the MAGOH-RONΔ160 axis, and these findings have important guiding significance and clinical value for the future development of effective therapeutic strategies for GC.
Sharenting: hidden pitfalls of a new increasing trend– suggestions on an appropriate use of social media
Authors: Gatto Antonio , Corsello Antonio , Ferrara Pietro
Published: January 2024

Background

The term “sharenting”, defining the practice of sharing children’s photos on social media, has become widespread globally. This phenomenon introduces new risks for children, often overlooked by parents lacking experience or caution in protecting their children from potential harms.

Main body

Parents share multimedia contents with positive intentions, but the lack of immediate risk perception prevails. An Italian study revealed that a significant percentage of parents (68%) frequently share their children’s photos on social platforms, often without considering potential risks. Pediatricians play a crucial role in raising awareness among parents regarding the dangers associated with online sharing and must empower families with defensive strategies to safeguard children’s privacy.

Conclusions

The commentary emphasizes the need for increased parental assistance in comprehending the risks of sharenting and using social media prudently. Pediatricians are pivotal in guiding parents, striking a balance between the natural urge to share children’s progress and an awareness of associated risks. Immediate action by scientific societies involves training and informing parents through various digital and print resources. A concrete regulation of this phenomenon is needed to protect children’s rights, but prioritizing digital awareness and education seems pivotal in mitigating sharenting-related risks.
New insight into the intravenous immunoglobulin treatment in Multisystem Inflammatory Syndrome in children and adults
Authors: Chen Chih-Jen , Kao Hsu-Yen , Huang Ching-Hua , Li Chia-Jung , Hung Cheng-Hsien , Yong Su-Boon
Published: January 2024

Within 6 months of the coronavirus pandemic, a new disease entity associated with a multisystem hyperinflammation syndrome as a result of a previous infection with the SARS-CoV-2 virus is increasingly being identified in children termed Multisystem Inflammatory Syndrome in Children (MIS-C) and more recently in adults(MIS-A). Due to its clinical similarity with Kawasaki Disease, some institutions have used intravenous immunoglobulins and steroids as first line agents in the management of the disease. We seek to find how effective intravenous immunoglobulin therapy is across these two disease entities. A comprehensive English literature search was conducted across PubMed, MEDLINE, and EMBASE databases using the keywords multisystem inflammatory syndrome in children/adults and treatment. All major online libraries concerning the diagnosis and treatment of MIS-C and MIS-A were searched. Relevant papers were read, reviewed, and analyzed. The use of intravenous immunoglobulins (IVIG) and steroids for the treatment of multisystemic inflammatory syndrome in children(MIS-C) is well established and recommended by multiple pediatric governing institutions. However, there is still no optimal treatment guideline or consensus on the use of IVIG in adults. The use of IVIG in both the child and adult populations may lower the risk of treatment failure and the need for adjunctive immunomodulatory therapy. Despite the promising results of IVIG use for the management of MIS-C and MIS-A, considering the pathophysiological differences between MIS-C and MIS-A, healthcare professionals need to further assess the differences in disease risk and treatment. The optimal dose, frequency, and duration of treatment are still unknown, more research is needed to establish treatment guidelines.
Effect of glycosylation on the affinity of the MTB protein Ag85B for specific antibodies: towards the design of a dual-acting vaccine against tuberculosis
Authors: Bernardini Roberta , Tengattini Sara , Li Zhihao , Piubelli Luciano , Bavaro Teodora , Modolea Anamaria Bianca , Mattei Maurizio , Conti Paola , Marini Stefano , Zhang Yongmin , Pollegioni Loredano , Temporini Caterina , Terreni Marco
Published: January 2024

Background

To create a dual-acting vaccine that can fight against tuberculosis, we combined antigenic arabino-mannan analogues with the Ag85B protein. To start the process, we studied the impact of modifying different parts of the Ag85B protein on its ability to be recognized by antibodies.

Results

Through our research, we discovered that three modified versions of the protein, rAg85B-K30R, rAg85B-K282R, and rAg85B-K30R/K282R, retained their antibody reactivity in healthy individuals and those with tuberculosis. To further test the specificity of the sugar AraMan for AraMan antibodies, we used Human Serum Albumin glycosylated with AraMan-IME and Ara3Man-IME. Our findings showed that this specific sugar was fully and specifically modified. Bio-panning experiments revealed that patients with active tuberculosis exhibited a higher antibody response to Ara3Man, a sugar found in lipoarabinomannan (LAM), which is a major component of the mycobacterial cell wall. Bio-panning with anti-LAM plates could eliminate this increased response, suggesting that the enhanced Ara3Man response was primarily driven by antibodies targeting LAM. These findings highlight the importance of Ara3Man as an immunodominant epitope in LAM and support its role in eliciting protective immunity against tuberculosis. Further studies evaluated the effects of glycosylation on the antibody affinity of recombinant Ag85B and its variants. The results indicated that rAg85B-K30R/K282R, when conjugated with Ara3Man-IME, demonstrated enhanced antibody recognition compared to unconjugated or non-glycosylated versions.

Conclusions

Coupling Ara3Man to rAg85B-K30R/K282R could lead to the development of effective dual-acting vaccines against tuberculosis, stimulating protective antibodies against both AraMan and Ag85B, two key tuberculosis antigens.
Improving the inclusion of an under-served group in trials: development and implementation of the INCLUDE Impaired Capacity to Consent Framework
Authors: Shepherd Victoria , Joyce Katherine , Lewis Amanda , Flynn Samantha , Clout Madeleine , Nocivelli Brittany , Segrott Jeremy , Treweek Shaun
Published: January 2024

Background

For the potential benefits of trials to reach all that they should, trials must be designed to ensure that those taking part reflect the population who will receive the intervention. However, adults with impaired capacity to consent are frequently excluded from trials — partly because researchers are unfamiliar with the legal and ethical frameworks and lack the necessary methodological expertise. Researchers identified a need for guidance on designing more inclusive trials. Building on the NIHR INCLUDE initiative, we developed the INCLUDE Impaired Capacity to Consent Framework to help researchers design inclusive trials.

Methods

The framework was developed over five phases: (1) establishing the scope and content of the framework and adapting the INCLUDE Ethnicity Framework for this population; (2) scoping the relevance of the framework to different populations and piloting in a range of trials; (3) consulting people living with impairing conditions and carers to explore their views about the framework and identify missing content areas; (4) refining the framework; and (5) the development of an implementation toolkit of resources to support researchers using the framework.

Results

The framework has two parts: a set of four key questions to help researchers identify who should be included in their trial, and a series of worksheets covering intervention design, recruitment and consent processes, data collection and analysis, and public involvement and dissemination. It is supported by a summary of the ethical and legal frameworks and a website of resources on capacity and consent. Implementation resources include infographics and animations, a library of completed frameworks, and facilitated workshops for researchers.

The framework and toolkit were launched at a webinar (November 2022), with polling demonstrating an increase in attendees’ awareness about research involving adults lacking capacity. A post-webinar survey found that stakeholders viewed the framework and toolkit as valuable tools to facilitate greater inclusion of this under-served population in trials. The framework is available online: https://www.capacityconsentresearch.com/include-impaired-capacity-to-consent-framework.html.

Conclusions

The INCLUDE Impaired Capacity to Consent Framework and implementation toolkit can support researchers to design more inclusive trials and other types of research studies. Further engagement, including with funders who are key to ensuring uptake, and evaluation is needed.
Kdr genotyping and the first report of V410L and V1016I kdr mutations in voltage-gated sodium channel gene in Aedes aegypti (Diptera: Culicidae) from Iran
Authors: Enayati Ahmadali , Valadan Reza , Bagherzadeh Mahboobeh , Cheraghpour Mohammad , Nikookar Seyed Hassan , Fazeli-Dinan Mahmoud , Hosseini-Vasoukolaei Nasibeh , Sahraei Rostami Farzaneh , Shabani Kordshouli Razieh , Raeisi Ahmad , Nikpour Fatemeh , Mirolyaei Abdolreza , Bagheri Fatemeh , Sedaghat Mohammad Mehdi , Zaim Morteza , Weetman David , Hemigway Janet
Published: January 2024

Background

Aedes aegyptiis the main vector of arboviral diseases worldwide. The species invaded and became established in southern Iran in 2020. Insecticide-based interventions are primarily used for its control. With insecticide resistance widespread, knowledge of resistance mechanisms is vital for informed deployment of insecticidal interventions, but information from IranianAe. aegyptiis lacking.

Methods

Fifty-sixAe. aegyptispecimens were collected from the port city of Bandar Lengeh in Hormozgan Province in the South of Iran in 2020 and screened forkdrmutations. The most commonkdrmutations in Latin America and Asia (V410L, S989P, V1016G/I and F1534C), especially when present in combinations, are highly predictive of DDT and pyrethroid resistance were detected. Phylogenetic analyses based on the diversity of S989P and V1016G/I mutations were undertaken to assess the phylogeography of thesekdrmutations.

Results

Genotyping all fourkdrpositions of V410L, S989P, V1016G/I and F1534C revealed that only 16 out of the 56 (28.57%) specimens were homozygous wild type for allkdrmutation sites. Six haplotypes including VSVF (0.537), VSVC (0.107), LSVF (0.016), LSIF (0.071), VPGC (0.257) and LPGC (0.011) were detected in this study. For the first time, 11 specimens harbouring the V410L mutation, and 8 samples with V1016I mutation were found. V410L and V1016I were coincided in 8 specimens. Also, six specimens contained 1016G/I double mutation which was not reported before.

Conclusions

The relatively high frequency of thesekdrmutations in IranianAe. aegyptiindicates a population exhibiting substantial resistance to pyrethroid insecticides, which are used widely in control operations and household formulations. The detection of the 410L/1016Ikdrmutant haplotype in IranianAe. aegyptisuggests possible convergence of invasive populations from West Africa or Latin America. However, as Iran has very limited maritime/air connections with those African countries, a Latin American origin for the invasiveAe. aegyptiin Iran is more plausible.

Graphical abstract
Comparison of three doses of amikacin on alternate days with a daily dose of meropenem during the same period for the treatment of urinary tract infection with E. coli: a double-blind clinical trial
Authors: Mohsenpour Behzad , Ahmadi Amjad , Azizzadeh Hero , Ghaderi Ebrahim , Hajibagheri Katayon , Afrasiabian Shahla , Lotfi Gohar , Farzinpoor Zhila
Published: January 2024

Objectives

Urinary tract infections (UTIs) are very common infections in humans, and Escherichia coli (E. coli) is the commonest pathogen leading to UTIs. The generation of beta-lactamase enzymes in this bacterium results in its resistance against many antibiotics. This study compares three doses of amikacin on alternate days with a daily dose of meropenem in the same period for the treatment of UTIs with E. coli in a double-blind clinical trial.

Methods

The current double-blind clinical trial compares three doses of amikacin on alternate days with a daily dose of meropenem in the same period for the treatment of UTIs with E. coli. The patients were assigned to two groups: Intervention (receiving a single dose of amikacin once a day at 48-h intervals for a week, three doses) and control (receiving meropenem for 1/TDS for a week).

Results

The E. coli infection frequency was 61 (21 cases of non-ESBL and 40 cases of ESBL-positive infections) and the frequency of the other infections was 52 (46%). In the patients with ESBL E. coli infection, ciprofloxacin (21; 70%) showed the highest antibiotic resistance, and nitrofurantoin (33; 91.7%) showed the highest sensitivity. The baseline variables between the control and intervention groups indicated no significant difference (p > 0.05). The frequency of signs and symptoms showed no significant difference between the amikacin and meropenem groups in the first 24 h and the first week. In the second week of follow-up, no clinical signs or symptoms were observed in the two groups.

Conclusion

The results of this study showed that treatment with amikacin, 1 g q48h, for one week (three doses) has the same result as meropenem, 1 g q8h, for one week (21 doses). The results are the same for the treatment of UTIs with ESBL positive and ESBL negative. Amikacin can be used once every 48 h to treat UTIs, is less expensive and can be administered on an outpatient basis.

Trial registration

This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20170417033483N2 on the date 2018-02-13.
Preoperative CT-based deep learning radiomics model to predict lymph node metastasis and patient prognosis in bladder cancer: a two-center study
Authors: Sun Rui , Zhang Meng , Yang Lei , Yang Shifeng , Li Na , Huang Yonghua , Song Hongzheng , Wang Bo , Huang Chencui , Hou Feng , Wang Hexiang
Published: January 2024

Objective

To establish a model for predicting lymph node metastasis in bladder cancer (BCa) patients.

Methods

We retroactively enrolled 239 patients who underwent three-phase CT and resection for BCa in two centers (training set, n = 185; external test set, n = 54). We reviewed the clinical characteristics and CT features to identify significant predictors to construct a clinical model. We extracted the hand-crafted radiomics features and deep learning features of the lesions. We used the Minimum Redundancy Maximum Relevance algorithm and the least absolute shrinkage and selection operator logistic regression algorithm to screen features. We used nine classifiers to establish the radiomics machine learning signatures. To compensate for the uneven distribution of the data, we used the synthetic minority over-sampling technique to retrain each machine-learning classifier. We constructed the combined model using the top-performing radiomics signature and clinical model, and finally presented as a nomogram. We evaluated the combined model’s performance using the area under the receiver operating characteristic, accuracy, calibration curves, and decision curve analysis. We used the Kaplan–Meier survival curve to analyze the prognosis of BCa patients.

Results

The combined model incorporating radiomics signature and clinical model achieved an area under the receiver operating characteristic of 0.834 (95% CI: 0.659–1.000) for the external test set. The calibration curves and decision curve analysis demonstrated exceptional calibration and promising clinical use. The combined model showed good risk stratification performance for progression-free survival.

Conclusion

The proposed CT-based combined model is effective and reliable for predicting lymph node status of BCa patients preoperatively.

Critical relevance statement

Bladder cancer is a type of urogenital cancer that has a high morbidity and mortality rate. Lymph node metastasis is an independent risk factor for death in bladder cancer patients. This study aimed to investigate the performance of a deep learning radiomics model for preoperatively predicting lymph node metastasis in bladder cancer patients.

Key points

• Conventional imaging is not sufficiently accurate to determine lymph node status.

• Deep learning radiomics model accurately predicted bladder cancer lymph node metastasis.

• The proposed method showed satisfactory patient risk stratification for progression-free survival.

Graphical Abstract
A matched case-control study of early cervical spondylotic myelopathy based on diffusion magnetic resonance imaging
Authors: Ni Ming , Li Shujing , Wen Xiaoyi , Wang Ben , Jiang Chenyu , Zhang Xianchang , Lang Ning , Jiang Liang , Yuan Huishu
Published: January 2024

Background

Early cervical spondylotic myelopathy (CSM) is challenging to diagnose and easily missed. Diffusion MRI (dMRI) has the potential to identify early CSM.

Methods

Using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI), a 1:1 matched case-control study was conducted to evaluate the potential of dMRI in identifying early CSM and assessing uncompressed segments of CSM patients. CSM patients and volunteers were matched by age and spinal location. The differences in dMRI parameters between groups were assessed by the paired t-test, the multicollinearity of the dMRI parameters was evaluated by the variance inflation factor (VIF), and the value of dMRI parameters in distinguishing controls from CSM patients was determined by logistic regression. The univariate t-test was used to analyse differences between CSM patients and volunteers in adjacent uncompressed areas.

Results

In total, 56 CSM patients and 56 control volunteers were included. Paired t-tests revealed significant differences in nine dMRI parameters between groups. Multicollinearity calculated through VIF and combined with logistic regression showed that the orientation division index (ODI) was significantly positively correlated (r = 2.12, p = 0.035), and the anisotropic water fraction (AWF) was significantly negatively correlated (r = −0.98, p = 0.015). The fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), isotropic volume fraction (ISOVF), ODI, and AWF were significantly different in the upper and lower uncompressed areas at all ages.

Conclusion

dMRI can noninvasively identify early CSM patients and potentially identify the extent of CSM lesions involving the cervical spinal cord.

Critical relevance statement

Diffusion MRI (dMRI) can identify early cervical spondylotic myelopathy (CSM) and has the potential to help determine the extent of CSM involvement. The application of dMRI can help screen for early CSM and develop clinical surgical and rehabilitation treatment plans.

Key points

• Diffusion MRI can differentiate between normal and early-stage cervical spondylotic myelopathy patients.

• Diffusion MRI has the ability to identify the extent of spinal cord involvement in cervical spondylotic myelopathy.

• Diffusion MRI enables the early screening of cervical spondylotic myelopathy and helps guide clinical treatment.

Graphical Abstract
Blow-up solutions for a 4-dimensional semilinear elliptic system of Liouville type in some general cases
Authors: Baraket Sami , Ghorbal Anis Ben , Chetouane Rima , Grine Azedine
Published: January 2024

This paper is devoted to the existence of singular limit solutions for a nonlinear elliptic system of Liouville type under Navier boundary conditions in a bounded open domain of $\mathbb{R}^{4}$

R
4

. The concerned results are obtained employing the nonlinear domain decomposition method and a Pohozaev-type identity.
Least energy nodal solutions for a weighted $(N, p)$-Schrödinger problem involving a continuous potential under exponential growth nonlinearity
Authors: Baraket Sami , Dridi Brahim , Grine Azedine , Jaidane Rached
Published: January 2024

This article aims to investigate the existence of nontrivial solutions with minimal energy for a logarithmic weighted $(N,p)$
(
N
,
p
)
-Laplacian problem in the unit ball B of $\mathbb{R}^{N}$

R
N

, $N>2$
N
>
2
. The nonlinearities of the equation are critical or subcritical growth, which is motivated by weighted Trudinger–Moser type inequalities. Our approach is based on constrained minimization within the Nehari set, the quantitative deformation lemma, and degree theory results.
Reported antibiotic use among patients in the multicenter ANDEMIA infectious diseases surveillance study in sub-saharan Africa
Authors: Wieters Imke , Johnstone Siobhan , Makiala-Mandanda Sheila , Poda Armel , Akoua-Koffi Chantal , Abu Sin Muna , Eckmanns Tim , Galeone Valentina , Kaboré Firmin Nongodo , Kahwata François , Leendertz Fabian H. , Mputu Benoit , Ouedraogo Abdoul-Salam , Page Nicola , Schink Susanne B. , Touré Fidèle Sounan , Traoré Adjaratou , Venter Marietjie , Vietor Ann Christin , Schubert Grit , Tomczyk Sara
Published: January 2024

Background

Exposure to antibiotics has been shown to be one of the drivers of antimicrobial resistance (AMR) and is critical to address when planning and implementing strategies for combatting AMR. However, data on antibiotic use in sub-Saharan Africa are still limited. Using hospital-based surveillance data from the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA), we assessed self-reported antibiotic use in multiple sub-Saharan African countries.

Methods

ANDEMIA included 12 urban and rural health facilities in Côte d’Ivoire, Burkina Faso, Democratic Republic of the Congo, and Republic of South Africa. Patients with acute respiratory infection (RTI), acute gastrointestinal infection (GI) and acute febrile disease of unknown cause (AFDUC) were routinely enrolled, and clinical, demographic, socio-economic and behavioral data were collected using standardized questionnaires. An analysis of ANDEMIA data from February 2018 to May 2022 was conducted. Reported antibiotic use in the ten days prior to study enrolment were described by substance and by the WHO AWaRe classification (“Access”, “Watch”, “Reserve”, and “Not recommended” antibiotics). Frequency of antibiotic use was stratified by location, disease syndrome and individual patient factors.

Results

Among 19,700 ANDEMIA patients, 7,258 (36.8%) reported antibiotic use. A total of 9,695 antibiotics were reported, including 54.7% (n = 5,299) from the WHO Access antibiotic group and 44.7% (n = 4,330) from the WHO Watch antibiotic group. The Watch antibiotic ceftriaxone was the most commonly reported antibiotic (n = 3,071, 31.7%). Watch antibiotic use ranged from 17.4% (56/322) among RTI patients in Côte d’Ivoire urban facilities to 73.7% (630/855) among AFDUC patients in Burkina Faso urban facilities. Reported antibiotic use included WHO Not recommended antibiotics but no Reserve antibiotics.

Conclusions

Reported antibiotic use data from this multicenter study in sub-Saharan Africa revealed a high proportion of WHO Watch antibiotics. Differences in Watch antibiotic use were found by disease syndrome, country and health facility location, which calls for a more differentiated approach to antibiotic use interventions including further evaluation of accessibility and affordability of patient treatment.
Association between visceral adiposity and generalized anxiety disorder (GAD)
Authors: Nameni Ghazaleh , Jazayeri Shima , Salehi Masoud , Esrafili Ali , Hajebi Ahmad , Motevalian Seyed Abbas
Published: January 2024

Background and objectives

Due to an increased rate of inflammation in generalized anxiety disorder (GAD), insight into the mediating factors in the onset and recurrence of the inflammatory response can help to achieve novel treatments for alleviating the risk of GAD. In the current study, we aimed to evaluate the possible relationship between visceral adipose tissue (VAT) as an important intermediary in inflammation pathways and GAD in participants of the Employees’ Health Cohort Study of Iran (EHCSIR).

Method

We analyzed the data from 3889 included participants aged > 18 years in the EHCSIR study, which were collected from 2017 to 2020. Lifetime and 12-month GAD were assessed using the Composite International Diagnostic Interview (CIDI-2.1) questionnaire. The adjusted prevalence ratio was computed to evaluate the association between GAD and visceral adiposity index (VAI), GAD and visceral fat area (VFA), GAD and body mass index (BMI) and ultimately GAD and waist circumference (WC) in males and females using STATA software.

Results

Log-binomial analysis showed a higher prevalence ratio of 12-month GAD associated with VFA in women [PR: 1.42, CI: 1.07–1.87, P: 0.015]. The prevalence of lifetime GAD was higher in obese women (BM1 > 30) [PR: 2.35, CI: 1.07–5.13, P:0.03] than in women with normal BMI. Women with higher VAI were also significantly more likely to suffer lifetime GAD [PR: 1.25, CI: 1.05]. 1.48, P:0.01]. In males, the prevalence of lifetime diagnosed GAD per 1 standard deviation increase in VFA was 0.65 [CI: 0.46–0.91, P: 0.01].

Conclusion

Visceral adiposity as a positive agent was associated with GAD prevalence in women. The presence of GAD symptoms showed no relationship to VFA in men.
Crustal density structure investigation of the East China Sea and adjacent regions using wavenumber domain 3D density imaging method
Authors: He Huiyou , Sun Heping , Fang Jian , Guo Dongmei , Li Jinbo
Published: January 2024

The East China Sea, situated at the intersection of the Eurasian, Philippine Sea, and Pacific plates, is characterized by complex geology influenced by tectonic phenomena such as plate movements, volcanism, faults, and uplifts. Crustal density structure inversion provides a thorough understanding of the region's geological history as well as Earth's dynamical evolution, providing critical insights into seismic disaster mitigation, resource exploration, marine environmental protection, and maritime safety. The inversion process, on the other hand, presents challenges in data quality, quantity, model complexity, uncertainty, and computational resources. With the advancement of next-generation satellite gravity measurements and developing inversion techniques, the inversion of marine crustal density structures promises to be more precise and comprehensive. We explored the density distribution in the East China Sea and surrounding areas using an innovative wavenumber domain three-dimensional density imaging method along with high-precision global satellite gravity data. By overcoming data quality and computing resource constraints, wavenumber domain three-dimensional density imaging has transformed the discipline of marine geophysics, successfully delivering accurate density distributions in the study area. We were able to get a more precise and comprehensive characterization of the crustal density structure by combining high-precision satellite gravity data and cutting-edge imaging methods. Our investigation has unveiled previously unknown details about density distribution in the East China Sea and its environs. The East China Sea shelf displays smooth low-density perturbations at 18 km depth, whereas the trench–arc–basin region exhibits increasing density perturbations. Notably, the Okinawa Trough, which is surrounded by the Tokara Volcanic Ridge and the Ryukyu Trench, displays strong positive anomalies with a north–northeastern to northeastern orientation. In contrast, the Ryukyu Ridge and the Philippine Sea Basin exhibit smaller negative values and substantial northwestward positive density trends, respectively. These findings indicate diverse material distribution, which provides important insights into the area’s geological evolution and tectonic processes. This study adds new insights into density distribution in the East China Sea and adjacent regions, offering information on the geological complexity of the region. The research lays the groundwork for future research on crustal dynamics and enhances the field of marine geophysics and related disciplines.

Graphical abstract
Relationship between animal-based on-farm indicators and meat inspection data in pigs
Authors: Witt Johanna , Krieter Joachim , Büttner Kathrin , Wilder Thore , Hasler Mario , Bussemas Ralf , Witten Stephanie , Czycholl Irena
Published: January 2024

Background

This study aimed to validate slaughterhouse indicators collected during meat inspection as an alternative to on-farm animal welfare indicators. For this purpose, the assessments of twelve on-farm and seven slaughterhouse indicators of 628 pigs from three different farms were combined into three indices, differentiated between on-farm and slaughterhouse: (1) limb health, (2) other organ health, and (3) respiratory health. At first, an assessment at animal-level using agreement parameters was carried out to ascertain whether the same welfare or health issues were identified on-farm and at slaughterhouse, taking the production period (farrowing, rearing and fattening period) and the last weeks before slaughtering into account. Second, the connection of slaughterhouse findings on the individual on-farm health indices was examined using logistic regressions, to determine whether certain welfare issues can be better monitored using slaughterhouse indicators.

Results

Acceptable agreement was determined using the Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) for the farrowing and fattening period, but not for the rearing period. A more detailed analysis of the weeks before slaughter shows that there is still a poor agreement 8 weeks before slaughter and an acceptable agreement 4 weeks before slaughter. This indicated the slaughterhouse indicators pneumonia, pleuritis and pericarditis as possible estimators of fever and deviant behavior on-farm and the slaughterhouse indicators bursitis and joint inflammations as possible estimators of lameness. In the second part of the analysis, the connection of slaughterhouse findings on the individual on-farm health indices was investigated; a significant influence of the farm on the limb and respiratory indices and no significant influence of the slaughterhouse findings could be determined, provided that all weekly assessments during the lifetime of the pigs have been taken into account. However, an influence of the slaughterhouse findings on the respiratory index and on the other organ index could be determined if only the weekly assessments four and eight weeks before slaughter, respectively, were taken into account.

Conclusions

In general, the possible suitable indicators detected by the PABAK, could replace some health-related indicators but a complete substitution of on-farm welfare assessment is not possible. In addition, the traceability over time must be investigated further.
Comprehensive analysis revealed the immunoinflammatory targets of rheumatoid arthritis based on intestinal flora, miRNA, transcription factors, and RNA-binding proteins databases, GSEA and GSVA pathway observations, and immunoinfiltration typing
Authors: Guan Yin , Zhang Yue , Zhao Xiaoqian , Wang Yue
Published: January 2024

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. This study aimed to identify potential biomarkers and possible pathogenesis of RA using various bioinformatics analysis tools.

Methods

The GMrepo database provided a visual representation of the analysis of intestinal flora. We selected the GSE55235 and GSE55457 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) separately. With the intersection of these DEGs with the target genes associated with RA found in the GeneCards database, we obtained the DEGs targeted by RA (DERATGs). Subsequently, Disease Ontology, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes were used to analyze DERATGs functionally. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on the data from the gene expression matrix. Additionally, the protein-protein interaction network, transcription factor (TF)-targets, target-drug, microRNA (miRNA)-mRNA networks, and RNA-binding proteins (RBPs)-DERATGs correlation analyses were built. The CIBERSORT was used to evaluate the inflammatory immune state. The single-sample GSEA (ssGSEA) algorithm and differential analysis of DERATGs were used among the infiltration degree subtypes.

Results

There were some correlations between the abundance of gut flora and the prevalence of RA. A total of 54 DERATGs were identified, mainly related to immune and inflammatory responses and immunodeficiency diseases. Through GSEA and GSVA analysis, we found pathway alterations related to metabolic regulations, autoimmune diseases, and immunodeficiency-related disorders. We obtained 20 hub genes and 2 subnetworks. Additionally, we found that 39 TFs, 174 drugs, 2310 miRNAs, and several RBPs were related to DERATGs. Mast, plasma, and naive B cells differed during immune infiltration. We discovered DERATGs’ differences among subtypes using the ssGSEA algorithm and subtype grouping.

Conclusions

The findings of this study could help with RA diagnosis, prognosis, and targeted molecular treatment.
Assessment of perinatal anxiety: diagnostic accuracy of five measures
Authors: Ayers Susan , Coates Rose , Sinesi Andrea , Cheyne Helen , Maxwell Margaret , Best Catherine , McNicol Stacey , Williams Louise R. , Uddin Nazihah , Hutton Una , Howard Grace , Shakespeare Judy , Walker James J. , Alderdice Fiona , Jomeen Julie ,   the MAP Study Team
Published: January 2024

Background

Anxiety in pregnancy and after giving birth (the perinatal period) is highly prevalent but under-recognised. Robust methods of assessing perinatal anxiety are essential for services to identify and treat women appropriately.

Aims

To determine which assessment measures are most psychometrically robust and effective at identifying women with perinatal anxiety (primary objective) and depression (secondary objective).

Method

We conducted a prospective longitudinal cohort study of 2243 women who completed five measures of anxiety and depression (Generalized Anxiety Disorder scale (GAD) two- and seven-item versions; Whooley questions; Clinical Outcomes in Routine Evaluation (CORE-10); and Stirling Antenatal Anxiety Scale (SAAS)) during pregnancy (15 weeks, 22 weeks and 31 weeks) and after birth (6 weeks). To assess diagnostic accuracy a sample of 403 participants completed modules of the Mini-International Neuropsychiatric Interview (MINI).

Results

The best diagnostic accuracy for anxiety was shown by the CORE-10 and SAAS. The best diagnostic accuracy for depression was shown by the CORE-10, SAAS and Whooley questions, although the SAAS had lower specificity. The same cut-off scores for each measure were optimal for identifying anxiety or depression (SAAS ≥9; CORE-10 ≥9; Whooley ≥1). All measures were psychometrically robust, with good internal consistency, convergent validity and unidimensional factor structure.

Conclusions

This study identified robust and effective methods of assessing perinatal anxiety and depression. We recommend using the CORE-10 or SAAS to assess perinatal anxiety and the CORE-10 or Whooley questions to assess depression. The GAD-2 and GAD-7 did not perform as well as other measures and optimal cut-offs were lower than currently recommended.
Solomon Islands Oncology Unit: Sustainability in Terms of Outcomes
Authors: Bush Dylan , Love Mark , Bugoro Hugo , Panda Nixon
Published: January 2024

Bush et al emphasize that the key to establishing enduring and efficient global health systems lies in prioritizing local stakeholders and, above all, the welfare of patients.
Characteristics and Survival Outcomes of Patients With Metastatic RET Fusion–Positive Solid Tumors Receiving Non-RET Inhibitor Standards of Care in a Real-World Setting
Authors: Hackshaw Allan , Fajardo Otto , Dafni Urania , Gelderblom Hans , Garrido Pilar , Siena Salvatore , Taylor Matthew H. , Bordogna Walter , Nikolaidis Christos
Published: January 2024

PURPOSE

RET fusions are oncogenic drivers across different solid tumors. However, the genomic landscape and natural history of patients with RET fusion–positive solid tumors are not well known. We describe the clinical characteristics of RET tyrosine kinase inhibitor (TKI)-naïve patients with RET fusion–positive solid tumors (excluding non–small-cell lung cancer [NSCLC]), treated in a real-world setting and assess the prognostic effect of RET fusions.

METHODS

Data for RET TKI-naïve patients with metastatic solid tumors (excluding NSCLC) who had ≥one Foundation Medicine comprehensive genomic profiling test (January 1, 2011-March 31, 2022) were obtained from a deidentified nationwide (US-based) clinicogenomic database. The primary objective of this study was to compare the overall survival (OS) of patients with RET fusion–positive tumors versus matched patients with RET wild-type ( RET-WT) tumors. Patients with RET-WT solid tumors were matched (4:1) to patients with RET fusion–positive tumors on the basis of preselected covariates.

RESULTS

The study population included 26 patients in the RET fusion–positive cohort, 7,220 patients in the RET-WT cohort (before matching), and 104 patients in the matched RET-WT cohort. Co-occurring genomic alterations were rare in the RET fusion–positive cohort. Median OS was consistently lower in patients with RET fusion–positive tumors versus those with RET-WT tumors, using three different analyses (hazard ratios, 2.0, 1.7, and 2.2).

CONCLUSION

These data suggest that RET fusions represent a negative prognostic factor in patients with metastatic solid tumors and highlight the need for wider genomic testing and use of RET-specific TKIs that could improve patient outcomes. Our study also highlights the value of real-world data when studying rare cancers or cancers with rare genomic alterations.
Effect of Thyroid Function on Offspring Neurodevelopment in People Receiving ART Therapy: A Prospective Cohort Study
Authors: Wang Haofeng , Peng Yuting , Xia Xinru , Jiang Yangqian , Du Jiangbo , Lv Hong , Ma Hongxia , Ma Xiang , Lin Yuan
Published: January 2024

Context

Adequate maternal thyroid hormone is vital for fetal neurodevelopment. Abnormal thyroid function can cause developmental defects in offspring from spontaneous pregnancies; however, research in assisted reproduction is lacking.

Objectives

This work aimed to investigate the association between thyroid disorders and offspring neurodevelopment from assisted reproduction.

Methods

In this prospective and longitudinal birth cohort study (Jiangsu, China), we included 729 women who had their thyroid function tested before an assisted reproductive technology cycle and delivered liveborn babies between November 2015 and June 2020. Maternal thyroid function was assessed by measuring thyroid antibodies, free thyroxine, and serum thyrotropin. The third edition Bayley Scales of Infant and Toddler Development screening test (Bayley-III screening test) was used to assess infant neurodevelopment.

Results

In multivariable-corrected linear regression analysis, infants of women with subclinical hypothyroidism (SCH) demonstrated a significantly lower receptive communication score (β = −.63; 95% CI, −1.12 to −0.14; P = .013), with stratified analysis showing a significant association among female offspring (β = −.87; 95% CI, −1.59 to −0.15; P = .018) but a null association among male offspring (β = −.44; 95% CI, −1.03 to 0.15; P = .145). No significant differences were found in the assisted pregnancy population with normal thyroid function and positive antibodies according to the diagnostic cutoffs applied to normal pregnant women.

Conclusion

SCH in assisted pregnancies correlates with lower communication scores in 1-year-olds, especially in girls. We recommend medication for SCH throughout, regardless of thyroid autoantibody status.
Low and Borderline Ankle–Brachial Index Is Associated With Intracranial Aneurysms: A Retrospective Cohort Study
Authors: Laukka Dan , Kangas Essi , Kuusela Aino , Hirvonen Jussi , Rissanen Tiia , Rahi Melissa , Kivelev Juri , Rantasalo Ville , Venermo Maarit , Rinne Jaakko , Hakovirta Harri
Published: January 2024

BACKGROUND AND OBJECTIVES:

A low ankle–brachial index (ABI) has been linked to systemic inflammation and an elevated risk of cardiovascular events, most notably myocardial infarction and stroke. Intracranial aneurysms (IAs) share similar risk factors with other cardiovascular diseases. However, the association between low ABI and IAs has not been sufficiently investigated. Our objective was to investigate the potential connection between ABI values and the prevalence of unruptured IAs.

METHODS:

This retrospective cohort study reviewed 2751 patients who had ABI measurements at a public tertiary hospital from January 2011 to December 2013. Patients with available cerebrovascular imaging or a diagnosis of ruptured IA were included in the study (n = 776) to examine the association between ABI and saccular IAs. The patients were classified into 4 groups: low ABI (≤0.9, n = 464), borderline ABI (0.91-0.99; n = 47), high ABI (>1.4, n = 57), and normal ABI (1.00-1.40; n = 208).

RESULTS:

The prevalence of IAs was 20.3% (18.1% unruptured IAs) in the low ABI group, 14.9% (12.8% unruptured IAs) in the borderline ABI group, 7.0% (5.3% unruptured IAs) in the high ABI group, and 2.4% (1.9% unruptured IAs) in the normal ABI group (P < .001). There were no significant differences in the prevalence of ruptured IAs between the ABI groups (P = .277). Sex- and age-adjusted multinomial regression, including clinically relevant variables, revealed that low ABI (odds ratio [OR], 13.02; 95% CI, 4.01-42.24), borderline ABI (OR, 8.68; 95% CI, 2.05-36.69), and smoking history (OR, 2.01; 95% CI, 1.07-3.77) were associated with unruptured IAs.

CONCLUSION:

The prevalence of unruptured IAs was 9-fold higher in the low ABI group and nearly 7-fold higher in the borderline ABI group when compared with the normal ABI group. ABI measurements could be clinically relevant for identifying individuals at higher risk of IAs and may help guide screening and preventive strategies.