bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis model of early Pneumocystis jirovecii pneumonia based on convolutional neural network: a comparison with traditional PCR diagnostic method
Authors: Li Yingying , Liu Hailin , Lv Qingwen , Long Jun
Published: April 2024

Background

Pneumocystis jirovecii pneumonia (PJP) is an interstitial pneumonia caused by pneumocystis jirovecii (PJ). The diagnosis of PJP primarily relies on the detection of the pathogen from lower respiratory tract specimens. However, it faces challenges such as difficulty in obtaining specimens and low detection rates. In the clinical diagnosis process, it is necessary to combine clinical symptoms, serological test results, chest Computed tomography (CT) images, molecular biology techniques, and metagenomics next-generation sequencing (mNGS) for comprehensive analysis.

Purpose

This study aims to overcome the limitations of traditional PJP diagnosis methods and develop a non-invasive, efficient, and accurate diagnostic approach for PJP. By using this method, patients can receive early diagnosis and treatment, effectively improving their prognosis.

Methods

We constructed an intelligent diagnostic model for PJP based on the different Convolutional Neural Networks. Firstly, we used the Convolutional Neural Network to extract CT image features from patients. Then, we fused the CT image features with clinical information features using a feature fusion function. Finally, the fused features were input into the classification network to obtain the patient's diagnosis result.

Results

In this study, for the diagnosis of PJP, the accuracy of the traditional PCR diagnostic method is 77.58%, while the mean accuracy of the optimal diagnostic model based on convolutional neural networks is 88.90%.

Conclusion

The accuracy of the diagnostic method proposed in this paper is 11.32% higher than that of the traditional PCR diagnostic method. The method proposed in this paper is an efficient, accurate, and non-invasive early diagnosis approach for PJP.
An observational study of quality of motion in the aging cervical spine: sequence of segmental contributions in dynamic fluoroscopy recordings
Authors: Schuermans Valérie N. E. , Smeets Anouk Y. J. M. , Breen Alexander , Branney Jonathan , Curfs Inez , van Santbrink Henk , Boselie Toon F. M.
Published: April 2024

Background

The term ‘physiological motion of the spine’ is commonly used although no proper definition exists. Previous work has revealed a consistent sequence of cervical segmental contributions in 80–90% of young healthy individuals. Age has been shown to be associated with a decreased quantity of motion. Therefore, it is of interest to study whether this sequence persists throughout aging.

The aim of this prospective cohort study is to investigate if the consistent sequence of cervical segmental contributions in young asymptomatic individuals remains present in elderly asymptomatic individuals.

Methods

In this prospective cohort study, dynamic flexion to extension cinematographic recordings of the cervical spine were made in asymptomatic individuals aged 55–70 years old. Individuals without neck pain and without severe degenerative changes were included. Two recordings were made in each individual with a 2-to-4-week interval (T1 and T2). Segmental rotation of each individual segment between C4 and C7 was calculated to determine the sequence of segmental contributions. Secondary outcomes were segmental range of motion (sRoM) and sagittal alignment.

Results

Ten individuals, with an average age of 61 years, were included. The predefined consistent sequence of segmental contributions was found in 10% of the individuals at T1 and 0% at T2. sRoM and total range of motion (tRoM) were low in all participants. There was no statistically significant correlation between sagittal alignment, degeneration and sRoM in the respective segments, nor between cervical lordosis and tRoM.

Conclusions

This study shows that aging is associated with loss of the consistent motion pattern that was observed in young asymptomatic individuals. The altered contribution of the cervical segments during extension did not appear to be correlated to the degree of degeneration or sagittal alignment.

Trial registration

clinicaltrials.gov NCT04222777, registered 10.01.2020.
Mid- and long-term clinical results of the Elektra and Moovis prosthesis for trapeziometacarpal joint replacement
Authors: Frey Pia-Elena , Bühner Christin , Falkner Florian , Harhaus Leila , Panzram Benjamin
Published: April 2024

Background

Total joint arthroplasty as a surgical treatment option for trapeziometacarpal joint arthritis is recently revived. The aim of this study is to report on mid- and long-term results of the Elektra (single-mobility) and Moovis (dual-mobility) prosthesis for treatment of primary thumb carpometacarpal joint arthritis.

Methods

In this retrospective, monocentric, descriptive cohort study, 31 prostheses were evaluated that were implanted by a single surgeon in 26 patients between 2009 and 2019. Indication for surgery was trapeziometacarpal joint osteoarthritis (Eaton/Littler Stage II and III). Clinical and radiological follow-up was performed at a minimum of 24 months. The postoperative assessment included range of motion, pain, strength as well as functional scores (DASH, MHQ). Implant survival and complications were the primary endpoints.

Results

10 Elektra and 21 Moovis prostheses were implanted between 2009 and 2019 with a mean follow-up of 74.2 months in the Elektra and 41.4 months in the Moovis group. The average patients’ age at surgery was 64 years. Postoperative pain levels (VAS 0–10) were below 2 at rest and under stress in both groups. Grip/pinch strength and range of motion showed results comparable to the contralateral hand. Opposition was excellent with an average Kapandji index of 9.6 in both groups. Elektra achieved slightly better functional scores in the DASH and MHQ score. Satisfaction was high in both groups, and 96% of the patients would recommend the procedure. Metacarpophalangeal hyperextension > 15° was seen in 3 patients per group preoperatively and was corrected to < 5° post-surgery. 3 Elektra prostheses were revised due to cup loosening and dislocation for cup and/or neck replacement or secondary trapeziectomy. 1 Moovis prosthesis was revised with an exchange of the neck to a larger size due to restricted movement. After the mean follow-up of 7.9 years in Elektra and 3.5 years in MOOVIS, cumulative survival was 68.6% vs. 95.2%, respectively.

Conclusions

In this mid- to long-term retrospective analysis, total joint arthroplasty in primary trapeziometacarpal joint arthritis results in low pain levels, excellent mobility and clinical function. Patient satisfaction is overall high. While revision due to cup loosening occurred more often in patients with single-mobility implants, no cases of dislocation or loosening of components were observed in the dual-mobility group.

Trial registration

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Medical Faculty of Heidelberg University, reference number S-150/2020.
INNBC DApp, a decentralized application to permanently store biomedical data on a modern, proof-of-stake (POS), blockchain such as BNB Smart Chain
Authors: Fior Jonathan
Published: April 2024

Background

A blockchain can be described as a distributed ledger database where, under a consensus mechanism, data are permanently stored in records, called blocks, linked together with cryptography. Each block contains a cryptographic hash function of the previous block, a timestamp, and transaction data, which are permanently stored in thousands of nodes and never altered. This provides a potential real-world application for generating a permanent, decentralized record of scientific data, taking advantage of blockchain features such as timestamping and immutability.

Implementation

Here, we propose INNBC DApp, a Web3 decentralized application providing a simple front-end user interface connected with a smart contract for recording scientific data on a modern, proof-of-stake (POS) blockchain such as BNB Smart Chain. Unlike previously proposed blockchain tools that only store a hash of the data on-chain, here the data are stored fully on-chain within the transaction itself as “transaction input data”, with a true decentralized storage solution. In addition to plain text, the DApp can record various types of files, such as documents, images, audio, and video, by using Base64 encoding. In this study, we describe how to use the DApp and perform real-world transactions storing different kinds of data from previously published research articles, describing the advantages and limitations of using such a technology, analyzing the cost in terms of transaction fees, and discussing possible use cases.

Results

We have been able to store several different types of data on the BNB Smart Chain: raw text, documents, images, audio, and video. Notably, we stored several complete research articles at a reasonable cost. We found a limit of 95KB for each single file upload. Considering that Base64 encoding increases file size by approximately 33%, this provides us with a theoretical limit of 126KB. We successfully overcome this limitation by splitting larger files into smaller chunks and uploading them as multi-volume archives. Additionally, we propose AES encryption to protect sensitive data. Accordingly, we show that it is possible to include enough data to be useful for storing and sharing scientific documents and images on the blockchain at a reasonable cost for the users.

Conclusion

INNBC DApp represents a real use case for blockchain technology in decentralizing biomedical data storage and sharing, providing us with features such as immutability, timestamp, and identity that can be used to ensure permanent availability of the data and to provide proof-of-existence as well as to protect authorship, a freely available decentralized science (DeSci) tool aiming to help bring mass adoption of blockchain technology among the scientific community.
Care-receivers with physical disabilities’ perceptions on having humanoid assistive robots as assistants: a qualitative study
Authors: Sørensen Linda , Johannesen Dag Tomas , Melkas Helinä , Johnsen Hege Mari
Published: April 2024

Background

People with physical disabilities due to disease or injury face barriers to their daily activities and participation in society. Many depend on formal or informal caregivers for assistance to live independently. However, future healthcare challenges due to demographic changes threaten access to home care and assistants. Assistive technologies, such as robots for physical assistance, can support the independence and autonomy of people with physical disabilities. This study explore Norwegian care-receivers’ perceptions of using robot assistance in their homes, including preferences for tasks acceptable or unacceptable for robot assistance and the underlying reasons.

Method

Purposive sampling was employed to recruit 18 participants, aged between 18 and 77 years, with differences in physical function including diagnoses such as stroke, spinal cord injury, amputations, and muscular dystrophy. Qualitative data were gathered through four focus group interviews wherein participants watched videos featuring a humanoid assistive robot, EVEr3. The collected data underwent analysis using reflexive thematic analysis.

Results

Three themes with associated sub-themes were constructed: (a) How a robot could assist in daily life, (b) The robot’s appearance and functionality, and (c) Concerns about having a robot as an assistant. The participants welcomed the idea of a future robotic assistant in areas that may contribute to an increased feeling of independence and autonomy.

Conclusion

A robot assisting in activities of daily living would need to be individually customized to meet the needs of each user in terms of which tasks to assist with, how to assist in these defined tasks, and how it is controlled.
Development and implementation of a treatment pathway to reduce coronary angiograms - lessons from a failure
Authors: Jung-Henrich Jutta , Schlößler Kathrin , Uebel Til , Chikhradze Nino , Suslow Anastasia , Lindner Nicole , Fahrenkrog Sandra , Kraft Judith , Hummers Eva , Vollmar Horst Christian , Gágyor Ildikó , Heider Dirk , König Hans-Helmut , Donner-Banzhoff Norbert
Published: April 2024

Background

The rates of coronary angiograms (CA) and related procedures (percutaneous intervention [PCI]) are significantly higher in Germany than in other Organisation for Economic Co-ordination and Development (OECD) countries. The current guidelines recommend non-invasive diagnosis of coronary heart disease (CHD); CA should only have a limited role in choosing the appropriate revascularisation procedure. The aim of the present study was to explore whether improvements in guideline adherence can be achieved through the implementation of regional treatment pathways. We chose four regions of Germany with high utilisation of CAs for the study. Here we report the results of the concomitant qualitative study.

Methods

General practitioners and specialist physicians (cardiologists, hospital-based cardiologists, emergency physicians, radiologists and nuclear medicine specialists) caring for patients with suspected CHD were invited to develop regional treatment pathways. Four academic departments provided support for moderation, provision of materials, etc. The study team observed session discussions and took notes. After the development of the treatment pathways, 45 semi-structured interviews were conducted with the participating physicians. Interviews and field notes were transcribed verbatim and underwent qualitative content analysis.

Results

Pathway development received little support among the participants. Although consensus documents were produced, the results were unlikely to improve practice. The participants expressed very little commitment to change. Although this attempt clearly failed in all study regions, our experience provides relevant insights into the process of evidence appraisal and implementation. A lack of organisational skills, ignorance of current evidence and guidelines, and a lack of feedback regarding one’s own clinical behaviour proved to be insurmountable. CA was still seen as the diagnostic gold standard by most interviewees.

Conclusions

Oversupply and overutilisation can be assumed to be present in study regions but are not immediately perceived by clinicians. The problem is unlikely to be solved by regional collaborative initiatives; optimised resource planning within the health care system combined with appropriate economic incentives might best address these issues.
Dysregulation of innate immune signaling in animal models of spinal muscular atrophy
Authors: Garcia Eric L. , Steiner Rebecca E. , Raimer Amanda C. , Herring Laura E. , Matera A. Gregory , Spring Ashlyn M.
Published: April 2024

Background

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the survival motor neuron (SMN) protein. SMA presents across a broad spectrum of disease severity. Unfortunately, genetic models of intermediate SMA have been difficult to generate in vertebrates and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes.

Results

Here, we carried out transcriptomic and proteomic profiling of mild and intermediate Drosophila models of SMA to elucidate molecules and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling. We find that mutation or tissue-specific depletion of SMN induces hyperactivation of the immune deficiency (IMD) and Toll pathways, leading to overexpression of antimicrobial peptides (AMPs) and ectopic formation of melanotic masses in the absence of an external challenge. Furthermore, the knockdown of downstream targets of these signaling pathways reduced melanotic mass formation caused by SMN loss. Importantly, we identify SMN as a negative regulator of a ubiquitylation complex that includes Traf6, Bendless, and Diap2 and plays a pivotal role in several signaling networks.

Conclusions

In alignment with recent research on other neurodegenerative diseases, these findings suggest that hyperactivation of innate immunity contributes to SMA pathology. This work not only provides compelling evidence that hyperactive innate immune signaling is a primary effect of SMN depletion, but it also suggests that the SMN complex plays a regulatory role in this process in vivo. In summary, immune dysfunction in SMA is a consequence of reduced SMN levels and is driven by cellular and molecular mechanisms that are conserved between insects and mammals.
Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes
Authors: Yan Han , Zhou Qing , Wang Yaqiong , Tu Yifan , Zhao Yuxin , Yu Jie , Chen Kuangyang , Hu Yepeng , Zhou Qiao , Zhang Wen , Zheng Chao
Published: April 2024

Background

This study was designed to assess the associations between emerging cardiometabolic indices—the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)—and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients.

Methods

We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis.

Results

A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02–1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12–1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42–2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52–3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532.

Conclusions

Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.
Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice
Authors: Sun Hai-Jian , Ni Zhang-Rong , Liu Yao , Fu Xiao , Liu Shi-Yi , Hu Jin-Yi , Sun Qing-Yi , Li Yu-Chao , Hou Xiao-Hui , Zhang Ji-Ru , Zhu Xue-Xue , Lu Qing-Bo
Published: April 2024

Background

Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored.

Methods

The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured.

Results

Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1.

Conclusions

NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.
Willingness to accept malaria vaccines amongst women presenting at outpatient and immunization clinics in Enugu state, Southeast Nigeria
Authors: Chinawa Awoere T. , Ossai Edmund N. , Onukwuli Vivian O. , Nduagubam Obinna C. , Uwaezuoke Ndubuisi A. , Okafor Chinyere N. , Chinawa Josephat M.
Published: April 2024

Background

There are giant steps taken in the introduction of the novel malaria vaccine poised towards reducing mortality and morbidity associated with malaria.

Objectives

This study aimed to determine the knowledge of malaria vaccine and factors militating against willingness to accept the vaccine among mothers presenting in nine hospitals in Enugu metropolis.

Methods

This was a cross-sectional study carried out among 491 mothers who presented with their children in nine hospitals in Enugu metropolis, South-East Nigeria. A pre-tested and interviewer-administered questionnaire was used in this study.

Results

A majority of the respondents, 72.1% were aware of malaria vaccine. A majority of the respondents, 83.1% were willing to receive malaria vaccine. Similarly, a majority of the mothers, 92.9%, were willing to vaccinate baby with the malaria vaccine, while 81.1% were willing to vaccinate self and baby with the malaria vaccine. The subjects who belong to the low socio-economic class were five times less likely to vaccinate self and baby with malaria vaccine when compared with those who were in the high socio-economic class (AOR = 0.2, 95% CI 0.1–0.5). Mothers who had good knowledge of malaria vaccination were 3.3 times more likely to vaccinate self and baby with malaria vaccine when compared with those who had poor knowledge of malaria vaccination (AOR = 3.3, 95% CI 1–6–6.8).

Conclusion

Although the study documented a high vaccine acceptance among the mothers, there exists a poor knowledge of the malaria vaccine among them.
MSC-derived mitochondria promote axonal regeneration via Atf3 gene up-regulation by ROS induced DNA double strand breaks at transcription initiation region
Authors: Zhang Yingchi , Xu Tao , Xie Jie , Wu Hua , Hu Weihua , Yuan Xuefeng
Published: April 2024

Background

The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear.

Methods

We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs).

Results

The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites.

Conclusion

These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.
Pan-cancer analysis implicates novel insights of lactate metabolism into immunotherapy response prediction and survival prognostication
Authors: Chen Dongjie , Liu Pengyi , Lu Xiongxiong , Li Jingfeng , Qi Debin , Zang Longjun , Lin Jiayu , Liu Yihao , Zhai Shuyu , Fu Da , Weng Yuanchi , Li Hongzhe , Shen Baiyong
Published: April 2024

Background

Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy.

Methods

Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments.

Results

The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy.

Conclusions

We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy.
Assessment of the in vitro acaricidal activity of Bravecto® (fluralaner) and a proposed orange oil-based formulation vehicle for the treatment of Sarcoptes scabiei
Authors: Takano Kotaro , Carver Scott , Vermaak Yolandi , Fischer Katja , Harvey Robert J. , Mounsey Kate E.
Published: April 2024

Background

Sarcoptic mange is a serious animal welfare concern in bare-nosed wombats (Vombatus ursinus). Fluralaner (Bravecto®) is a novel acaricide that has recently been utilised for treating mange in wombats. The topical ‘spot-on’ formulation of fluralaner can limit treatment delivery options in situ, but dilution to a volume for ‘pour-on’ delivery is one practicable solution. This study investigated the in vitro acaricidal activity of Bravecto, a proposed essential oil-based diluent (Orange Power®), and two of its active constituents, limonene and citral, againstSarcoptes scabiei.

Methods

Sarcoptes scabieiwere sourced from experimentally infested pigs. In vitro assays were performed to determine the lethal concentration (LC50) and survival time of the mites when exposed to varying concentrations of the test solutions.

Results

All compounds were highly effective at killing mites in vitro. The LC50values of Bravecto, Orange Power, limonene and citral at 1 h were 14.61 mg/ml, 4.50%, 26.53% and 0.76%, respectively. The median survival times of mites exposed to undiluted Bravecto, Orange Power and their combination were 15, 5 and 10 min, respectively. A pilot survival assay of mites collected from a mange-affected wombat showed survival times of < 10 min when exposed to Bravecto and Orange Power and 20 min when exposed to moxidectin.

Conclusions

These results confirm the acaricidal properties of Bravecto, demonstrate acaricidal properties of Orange Power and support the potential suitability of Orange Power and its active constituents as a diluent for Bravecto. As well as killing mites via direct exposure, Orange Power could potentially enhance the topical delivery of Bravecto to wombats by increasing drug penetration in hyperkeratotic crusts. Further research evaluating the physiochemical properties and modes of action of Orange Power and its constituents as a formulation vehicle would be of value.

Graphical Abstract
Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy
Authors: Lee Seulkee , Kang Seonyoung , Kim Hyungjin , Lee Jaejoon , Kim Min-Ji , Cha Hoon-Suk
Published: April 2024

Background

We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi).

Methods

Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA.

Results

This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200–2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678–1.455), after adjusting for other baseline characteristics.

Conclusions

The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.
Effect of the SARS-CoV-2 pandemic on metabolic control in patients with type 2 diabetes: a 5-year cohort follow-up managed by a dynamic multidisciplinary team in Northeastern Mexico
Authors: Morales-Rodriguez Devany Paola , González-Cantú Arnulfo , Garza-Silva Arnulfo , Rivera-Cavazos Andrea , Fernández-Chau Iván Francisco , Cepeda-Medina Andrea Belinda , Sanz-Sánchez Miguel Angel , del Rio-Parra Gerardo Francisco , Torres-Fuentes María Angelina , Rodriguez-Puente Miguel Assael , Romero-Ibarguengoitia Maria Elena
Published: April 2024

Background

The SARS-CoV-2 pandemic brought a radical shift in the healthcare system and suboptimal care for vulnerable patients, such as those with Type 2 Diabetes Mellitus (T2D). Therefore, we compared metabolic control and macro/microvascular complications of patients with T2D before and throughout the three-year SARS-CoV-2 pandemic.

Research design and methods

A retrospective observational cohort of subjects with T2D studied from 2018 to 2022 in Northern Mexico was treated by a dynamic multidisciplinary team. Levels of Glycated hemoglobin (HbA1c), fasting serum glucose (FG), LDL-Cholesterol (LDL-C), blood pressure (BP), albuminuria, triglycerides, Body Mass Index (BMI), and FIB-4 score, micro and macrovascular complications were evaluated.

Results

A total of 999 patients were studied, 51.7% males with a mean (SD) age of 60.1 (12.7) years. Adequate glycemic control based on HbA1c increased by 15.2% and 42.3% in FSG (p < 0.001) between the beginning 2018 and the end of 2022. LDL-C control decreased by 5.1% between 2018 and 2022 (p < 0.001). Systolic BP control decreased by 2.6% (p < 0.001), whereas diastolic BP control increased by 1.8% (p = 0.01) between 2018 and 2022. Albuminuria control increased by 8.5% (p = 0.002). When comparing the Area Under the Curve (AUC) of metabolic parameters between patients who developed SARS-CoV-2 vs. those who did not, AUC was statistically higher in those who developed SARS-CoV-2 (p < 0.05). Diabetic neuropathy was the most prevalent microvascular complication (n = 35; 3.6%); ischemic heart disease was the most frequent macrovascular complication (n = 11;1.1%).

Conclusions

A multidisciplinary dynamic team that adapts to the pandemic SARS-CoV-2 maintains and increases metabolic control in subjects with type 2 diabetes in Mexico. This represents a low percentage of chronic complications. The AUC of metabolic parameters of subjects with SARS-CoV-2 infection is higher, reflecting more variability in metabolic control.

Graphical Abstract
Evaluating Night-Eating Syndrome in bariatric surgery patients: A cross-sectional study
Authors: Almuammar Sarah , Aljaaly Elham , Alqarni Lama , Alazwari Hadeel , Alsubhi Ruba , Alatawi Nouf
Published: April 2024

Background

Night-Eating Syndrome (NES) is a complex eating disorder that has gained recognition in the context of bariatric surgery. However, its prevalence and associated factors in this specific patient population remain understudied, particularly in the Saudi Arabian context.

Methods

This cross-sectional study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, from June to November 2022. Adult patients who had undergone bariatric surgery with a postoperative follow-up of 6 months were included. NES was assessed using the Night Eating Questionnaire (NEQ).

Results

A total of 154 patients were enrolled in the study, with a mean age of 38.8 ± 11.4 years. The mean BMI before surgery was 44.8 ± 8.2 kg/m2, which reduced to 28.9 ± 5.8 kg/m2 post-surgery. Of these, 52 patients (33.8%) met the criteria for NES based on NEQ scores. The prevalence of NES was significantly higher among female patients, with 35 out of 83 females (42.2%) compared to 17 out of 71 males (23.9%) experiencing NES. While NES was not significantly associated with age, nationality, diet adherence, BMI, or surgery type, chronic diseases—particularly diabetes—emerged as significant risk factors for NES in post-bariatric surgery patients.

Conclusion

NES is a prevalent concern among post-bariatric surgery patients, with distinct associations with gender and chronic diseases, particularly diabetes. This study provides valuable insights into NES prevalence and its risk factors in the Saudi Arabian context, highlighting the importance of addressing eating disorders within the framework of bariatric surgery care.
A study about the impact of indoor air pollution on cognitive function among middle-aged and older adult people in India
Authors: Saha Subhadeep , Das Priya , Das Tanu , Das Partha , Roy Tamal Basu
Published: April 2024

Background

In the 21st century, people still use solid fuel for cooking at home, resulting in poor indoor air quality. Prolonged exposure to such conditions may negatively affect one’s cognitive function. So, the present study examines the possible association between IAP and the cognitive function of individuals aged 45 years or above in India.

Methods

The study utilizes secondary data, procured from the longitudinal ageing study in India (2017-18). Treatment effects through regression-adjusted models were applied to represent the association between IAP and cognitive health and the results are represented by beta coefficient (β). Three separate models with a 95% confidence interval adjusting with the other factors like housing environment, individual and behavioural were framed.

Results

The study revealed that households without a separate kitchen (β = -0.64; 95%CI: -0.90 to -0.39) and electricity (β = -0.97; 95%CI: -1.34 to -0.61) significantly affect cognitive strength. Cognitive decline is likely more pronounced among older adults (β = -1.19; 95%CI: -1.42 to -0.96) than the middle-aged population. Moreover, the cognitive ability of rural residents (β = -1.11; 95%CI: -1.49 to -0.73) and women (β = -2.05; 95%CI: -2.29 to -1.81) is negatively associated with IAP exposure. Older adults with no reading habits (β = -6.28; 95%CI: -6.72; to -5.85) and physical inactivity (β = -0.96; 95%CI: -1.22 to -0.70) had a sign of notable decline in cognitive ability.

Conclusions

Findings revealed that cognitive function is negatively associated with IAP, demanding a deep intervention plan to minimize the detrimental effect.
Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench
Authors: Dang Yan-Ru , Cha Qian-Qian , Liu Sha-Sha , Wang Shu-Yan , Li Ping-Yi , Li Chun-Yang , Wang Peng , Chen Xiu-Lan , Tian Ji-Wei , Xin Yu , Chen Yin , Zhang Yu-Zhong , Qin Qi-Long
Published: April 2024

Background

The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes.

Results

In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50–9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench.

Conclusions

Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench.
Assessing intersectional gender analysis in Nepal’s health management information system: a case study on tuberculosis for inclusive health systems
Authors: Parajuli Ayuska , Kakchapati Sampurna , Arjyal Abriti , Joshi Deepak , Kharel Chandani , Otmani del Barrio Mariam , Baral Sushil C
Published: April 2024

Background

Tuberculosis (TB) remains a major public health problem in Nepal, high in settings marked by prevalent gender and social inequities. Various social stratifiers intersect, either privileging or oppressing individuals based on their characteristics and contexts, thereby increasing risks, vulnerabilities and marganilisation associated with TB. This study aimed to assess the inclusiveness of gender and other social stratifiers in key health related national policies and the Health Management Information System (HMIS) of National Tuberculosis Programme (NTP) by conducting an intersectional analysis of TB cases recorded via HMIS.

Methods

A desk review of key policies and the NTP’s HMIS was conducted. Retrospective intersectional analysis utilized two secondary data sources: annual NTP report (2017–2021) and records of 628 TB cases via HMIS 6.5 from two TB centres (2017/18–2018/19). Chi-square test and multi-variate analysis was used to assess the association between social stratifers and types of TB, registration category and treatment outcome.

Results

Gender, social inclusion and concept of intersectionality are incorporated into various health policies and strategies but lack effective implementation. NTP has initiated the collection of age, sex, ethnicity and location data since 2014/15 through the HMIS. However, only age and sex disaggregated data are routinely reported, leaving recorded social stratifiers of TB patients static without analysis and dissemination. Furthermore, findings from the intersectional analysis using TB secondary data, showed that male more than 25 years exhibited higher odds [adjusted odds ratio (aOR) = 4.95, 95% confidence interval (CI): 1.60–19.06, P = 0.01)] of successful outcome compared to male TB patients less than 25 years. Similarly, sex was significantly associated with types of TB (P < 0.05) whereas both age (P < 0.05) and sex (P < 0.05) were significantly associated with patient registration category (old/new cases).

Conclusions

The results highlight inadequacy in the availability of social stratifiers in the routine HMIS. This limitation hampers the NTP’s ability to conduct intersectional analyses, crucial for unveiling the roles of other social determinants of TB. Such limitation underscores the need for more disaggregated data in routine NTP to better inform policies and plans contributing to the development of a more responsive and equitable TB programme and effectively addressing disparities.
Unveiling the dynamics of "scenes changing as steps move" in a Chinese classical garden: a case study of Jingxinzhai Garden
Authors: Chen Yujia , Gu Yang , Liu Yaxin , Cao Lei
Published: April 2024

Chinese classical gardens are a significant cultural heritage in the history of world gardening, with their central architectural principle of "scenes changing as steps move" (步移景异) embodying traditional Chinese aesthetic ideals. This study employed the variation of visual complexity during a tour as a representation of this principle, using Jingxinzhai (静心斋) Garden as a case study. The visual environmental characteristics were quantified using the Fraclab box-counting, Canny edge detection, and DeepLab V3 + model, and the spatial distribution of fractal dimension and visual index of landscape elements were analyzed. Through partial correlation analysis, hierarchical regression analysis, and one-way ANOVA, the relevant factors (BVI, RVI, GVI, WVI) and influencing factors (BVI, RVI, GVI) and the differences among landscape element combinations of visual complexity were identified. Furthermore, the distribution patterns and causes of visual complexity in Chinese classical gardens were then discussed. This study proposes an effective method for quantifying the visual environmental characteristics of Chinese classical gardens and provides an explanation of the concept of "scenes changing as steps move" from the perspective of visual environment. It offers important references for a deeper understanding of Chinese classical garden design and planning.