bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building a trustworthy AI differential diagnosis application for Crohn’s disease and intestinal tuberculosis
Authors: Lu Keming , Tong Yuanren , Yu Si , Lin Yucong , Yang Yingyun , Xu Hui , Li Yue , Yu Sheng 
Published: August 2023

Abstract
Background
Differentiating between Crohn’s disease (CD) and intestinal tuberculosis (ITB) with endoscopy is challenging. We aim to perform more accurate endoscopic diagnosis between CD and ITB by building a trustworthy AI differential diagnosis application.

Methods
A total of 1271 electronic health record (EHR) patients who had undergone colonoscopies at Peking Union Medical College Hospital (PUMCH) and were clinically diagnosed with CD (n = 875) or ITB (n = 396) were used in this study. We build a workflow to make diagnoses with EHRs and mine differential diagnosis features; this involves finetuning the pretrained language models, distilling them into a light and efficient TextCNN model, interpreting the neural network and selecting differential attribution features, and then adopting manual feature checking and carrying out debias training.

Results
The accuracy of debiased TextCNN on differential diagnosis between CD and ITB is 0.83 (CR F1: 0.87, ITB F1: 0.77), which is the best among the baselines. On the noisy validation set, its accuracy was 0.70 (CR F1: 0.87, ITB: 0.69), which was significantly higher than that of models without debias. We also find that the debiased model more easily mines the diagnostically significant features. The debiased TextCNN unearthed 39 diagnostic features in the form of phrases, 17 of which were key diagnostic features recognized by the guidelines.

Conclusion
We build a trustworthy AI differential diagnosis application for differentiating between CD and ITB focusing on accuracy, interpretability and robustness. The classifiers perform well, and the features which had statistical significance were in agreement with clinical guidelines.
Navigating language discordance in public health care in rural South Africa: a qualitative descriptive study of occupational therapists’ perspectives
Authors: Ramafikeng M. C. , Marshall E. 
Published: August 2023

Abstract
Background
Language discordance occurs in healthcare when staff and service users do not share proficiency in the same language. It is a global phenomenon impacting on the quality of health services, as person-centred practice requires communication to establish partnerships and rapport. In a country as linguistically diverse as South Africa, effective ways to navigate language discordance in health care are urgently required, yet there is limited research. This study aimed to describe how occupational therapists navigated language discordance when working in the public health sector in KwaZulu-Natal.

Methods
A qualitative descriptive design involved using purposive sampling to recruit occupational therapists as participants (n = 8) for 15 semi-structured interviews. Thematic analysis was used to analyse the data, which included reflective journal entries from all participants.

Results
The four emergent themes were: (1) concurrent use of strategies, (2) I’m doing as much I can, what more can I do? (3) Language definitely impacts that therapy process and lastly, (4) systemic oppression perpetuating language discordance.

Conclusion
Language discordance is a complex context-specific phenomenon, therefore insight into concurrent use of strategies is important to practitioners to enable them to navigate language discordance and ensure provision of quality services. These insights are significant for healthcare professionals and resource allocators as they shed light on the shortcomings of advocating for a single strategy such as providing trained interpreters. Successful navigation is characterised by determination, being kind to oneself, willingness to learn and use of pragmatic and flexible approaches. To prepare to navigate language discordance in a low-resource context, education should extend in time and scope, to include multiple strategies, culture and relevant languages.
Healthcare fragmentation, multimorbidity, potentially inappropriate medication, and mortality: a Danish nationwide cohort study
Authors: Prior Anders , Vestergaard Claus Høstrup , Vedsted Peter , Smith Susan M. , Virgilsen Line Flytkjær , Rasmussen Linda Aagaard , Fenger-Grøn Morten 
Published: August 2023

Abstract
Background
Patients with multimorbidity are frequent users of healthcare, but fragmented care may lead to suboptimal treatment. Yet, this has never been examined across healthcare sectors on a national scale. We aimed to quantify care fragmentation using various measures and to analyze the associations with patient outcomes.

Methods
We conducted a register-based nationwide cohort study with 4.7 million Danish adult citizens. All healthcare contacts to primary care and hospitals during 2018 were recorded. Clinical fragmentation indicators included number of healthcare contacts, involved providers, provider transitions, and hospital trajectories. Formal fragmentation indices assessed care concentration, dispersion, and contact sequence. The patient outcomes were potentially inappropriate medication and all-cause mortality adjusted for demographics, socioeconomic factors, and morbidity level.

Results
The number of involved healthcare providers, provider transitions, and hospital trajectories rose with increasing morbidity levels. Patients with 3 versus 6 conditions had a mean of 4.0 versus 6.9 involved providers and 6.6 versus 13.7 provider transitions. The proportion of contacts to the patient’s own general practice remained stable across morbidity levels. High levels of care fragmentation were associated with higher rates of potentially inappropriate medication and increased mortality on all fragmentation measures after adjusting for demographic characteristics, socioeconomic factors, and morbidity. The strongest associations with potentially inappropriate medication and mortality were found for ≥ 20 contacts versus none (incidence rate ratio 2.83, 95% CI 2.77–2.90) and ≥ 20 hospital trajectories versus none (hazard ratio 10.8, 95% CI 9.48–12.4), respectively. Having less than 25% of contacts with your usual provider was associated with an incidence rate ratio of potentially inappropriate medication of 1.49 (95% CI 1.40–1.58) and a mortality hazard ratio of 2.59 (95% CI 2.36–2.84) compared with full continuity. For the associations between fragmentation measures and patient outcomes, there were no clear interactions with number of conditions.

Conclusions
Several clinical indicators of care fragmentation were associated with morbidity level. Care fragmentation was associated with higher rates of potentially inappropriate medication and increased mortality even when adjusting for the most important confounders. Frequent contact to the usual provider, fewer transitions, and better coordination were associated with better patient outcomes regardless of morbidity level.
Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors
Authors: Stachura Paweł , Liu Wei , Xu Haifeng C. , Wlodarczyk Agnès , Stencel Olivia , Pandey Piyush , Vogt Melina , Bhatia Sanil , Picard Daniel , Remke Marc , Lang Karl S. , Häussinger Dieter , Homey Bernhard , Lang Philipp A. , Borkhardt Arndt , Pandyra Aleksandra A. 
Published: August 2023

Abstract
Background
New therapies are urgently needed in melanoma, particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors. To uncover novel potentiators of T cell anti-tumor immunity, we carried out an ex vivo pharmacological screen and identified 5-Nonyloxytryptamine (5-NL), a serotonin agonist, as increasing the ability of T cells to target tumor cells.

Methods
The pharmacological screen utilized lymphocytic choriomeningitis virus (LCMV)-primed splenic T cells and melanoma B16.F10 cells expressing the LCMV gp33 CTL epitope. In vivo tumor growth in C57BL/6 J and NSG mice, in vivo antibody depletion, flow cytometry, immunoblot, CRISPR/Cas9 knockout, histological and RNA-Seq analyses were used to decipher 5-NL’s immunomodulatory effects in vitro and in vivo.

Results
5-NL delayed tumor growth in vivo and the phenotype was dependent on the hosts’ immune system, specifically CD8+ T cells. 5-NL’s pro-immune effects were not directly consequential to T cells. Rather, 5-NL upregulated antigen presenting machinery in melanoma and other tumor cells in vitro and in vivo without increasing PD-L1 expression. Mechanistic studies indicated that 5-NL’s induced MHC-I expression was inhibited by pharmacologically preventing cAMP Response Element-Binding Protein (CREB) phosphorylation. Importantly, 5-NL combined with anti-PD1 therapy showed significant improvement when compared to single anti-PD-1 treatment.

Conclusions
This study demonstrates novel therapeutic opportunities for augmenting immune responses in poorly immunogenic tumors.
m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism
Authors: Yue Shi-Wei , Liu Hai-Ling , Su Hong-Fei , Luo Chu , Liang Hui-Fang , Zhang Bi-Xiang , Zhang Wei 
Published: August 2023

AbstractGlycolytic reprogramming is one of the most important features of cancer and plays an integral role in the progression of cancer. In cancer cells, changes in glucose metabolism meet the needs of self-proliferation, angiogenesis and lymphangiogenesis, metastasis, and also affect the immune escape, prognosis evaluation and therapeutic effect of cancer. The n6-methyladenosine (m6A) modification of RNA is widespread in eukaryotic cells. Dynamic and reversible m6A modifications are widely involved in the regulation of cancer stem cell renewal and differentiation, tumor therapy resistance, tumor microenvironment, tumor immune escape, and tumor metabolism. Lately, more and more evidences show that m6A modification can affect the glycolysis process of tumors in a variety of ways to regulate the biological behavior of tumors. In this review, we discussed the role of glycolysis in tumor genesis and development, and elaborated in detail the profound impact of m6A modification on different tumor by regulating glycolysis. We believe that m6A modified glycolysis has great significance and potential for tumor treatment.
HBO treatment enhances motor function and modulates pain development after sciatic nerve injury via protection the mitochondrial function
Authors: Awad-Igbaria Yaseen , Ferreira Nadine , Keadan Ali , Sakas Reem , Edelman Doron , Shamir Alon , Francous-Soustiel Jean , Palzur Eilam 
Published: August 2023

Abstract
Background
Peripheral nerve injury can cause neuroinflammation and neuromodulation that lead to mitochondrial dysfunction and neuronal apoptosis in the dorsal root ganglion (DRG) and spinal cord, contributing to neuropathic pain and motor dysfunction. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential therapeutic tool for neuropathic pain and nerve injury. However, the specific cellular and molecular mechanism by which HBOT modulates the development of neuropathic pain and motor dysfunction through mitochondrial protection is still unclear.

Methods
Mechanical and thermal allodynia and motor function were measured in rats following sciatic nerve crush (SNC). The HBO treatment (2.5 ATA) was performed 4 h after SNC and twice daily (12 h intervals) for seven consecutive days. To assess mitochondrial function in the spinal cord (L2–L6), high-resolution respirometry was measured on day 7 using the OROBOROS-O2k. In addition, RT-PCR and Immunohistochemistry were performed at the end of the experiment to assess neuroinflammation, neuromodulation, and apoptosis in the DRG (L3–L6) and spinal cord (L2–L6).

Results
HBOT during the early phase of the SNC alleviates mechanical and thermal hypersensitivity and motor dysfunction. Moreover, HBOT modulates neuroinflammation, neuromodulation, mitochondrial stress, and apoptosis in the DRG and spinal cord. Thus, we found a significant reduction in the presence of macrophages/microglia and MMP-9 expression, as well as the transcription of pro-inflammatory cytokines (TNFa, IL-6, IL-1b) in the DRG and (IL6) in the spinal cord of the SNC group that was treated with HBOT compared to the untreated group. Notable, the overexpression of the TRPV1 channel, which has a high Ca2+ permeability, was reduced along with the apoptosis marker (cleaved-Caspase3) and mitochondrial stress marker (TSPO) in the DRG and spinal cord of the HBOT group. Additionally, HBOT prevents the reduction in mitochondrial respiration, including non-phosphorylation state, ATP-linked respiration, and maximal mitochondrial respiration in the spinal cord after SNC.

Conclusion
Mitochondrial dysfunction in peripheral neuropathic pain was found to be mediated by neuroinflammation and neuromodulation. Strikingly, our findings indicate that HBOT during the critical period of the nerve injury modulates the transition from acute to chronic pain via reducing neuroinflammation and protecting mitochondrial function, consequently preventing neuronal apoptosis in the DRG and spinal cord.
Human nutritional relevance and suggested nutritional guidelines for vitamin A5/X and provitamin A5/X
Authors: Bohn Torsten , Hellman-Regen Julian , de Lera Angel R. , Böhm Volker , Rühl Ralph 
Published: August 2023

AbstractIn the last century, vitamin A was identified that included the nutritional relevant vitamin A1 / provitamin A1, as well as the vitamin A2 pathway concept. Globally, nutritional guidelines have focused on vitamin A1 with simplified recommendations and calculations based solely on vitamin A. The vitamin A / provitamin A terminology described vitamin A with respect to acting as a precursor of 11-cis-retinal, the chromophore of the visual pigment, as well as retinoic acid(s), being ligand(s) of the nuclear hormone receptors retinoic acid receptors (RARs) α, β and γ. All-trans-retinoic acid was conclusively shown to be the endogenous RAR ligand, while the concept of its isomer 9-cis-retinoic acid, being “the” endogenous ligand of the retinoid-X receptors (RXRs), remained inconclusive. Recently, 9-cis-13,14-dihydroretinoic acid was conclusively reported as an endogenous RXR ligand, and a direct nutritional precursor was postulated in 2018 and further confirmed by Rühl, Krezel and de Lera in 2021. This was further termed vitamin A5/X / provitamin A5/X. In this review, a new vitamin A5/X / provitamin A5/X concept is conceptualized in parallel to the vitamin A(1) / provitamin A(1) concept for daily dietary intake and towards dietary guidelines, with a focus on the existing national and international regulations for the physiological and nutritional relevance of vitamin A5/X. The aim of this review is to summarize available evidence and to emphasize gaps of knowledge regarding vitamin A5/X, based on new and older studies and proposed future directions as well as to stimulate and propose adapted nutritional regulations.
Spectrum subtraction as a complementary method for six resolution techniques resolving overlapping spectra; application to multicomponent veterinary formulation with greenness and whiteness assessment
Authors: Hagag Mahmoud G. , Hemdan Ahmed M. , Nadim Ahmed H. , Abbas Samah S. , Fahmy Nesma M. 
Published: August 2023

AbstractMathematical filtration is an efficient tool to resolve the overlapping spectra of binary mixtures in zero or first order form. Herein, a comparative study was conducted between six economic, accurate and precise spectrophotometric methods for determination of Triclabendazole (TCB) and Levamisole HCl (LVM). Each component was resolved with minimum mathematical steps in its zero-order absorption spectrum by ratio subtraction, constant multiplication, and the recent factorized response method; coupled with spectrum subtraction. In addition, the mixture was resolved in its first derivative form by derivative subtraction, D1 constant multiplication, and the recent D1 factorized response method; coupled with spectrum subtraction. Results obtained were also compared to those obtained from constant value, concentration value, and derivative ratio methods. The linearity range was found to be either 1.0–10.0 µg/mL or 2.0–20.0 µg/mL for TCB, and 2.0–14.0 µg/mL for LVM with LOD of 0.08 µg/mL and 0.19 µg/mL, respectively. Validation of the proposed methods was performed according to VICH guidelines. Results obtained from the statistical data showed no significant difference regarding accuracy and precision compared to the reported methods. The developed spectrophotometric methods followed the principles of green analytical chemistry, in which the green assessment was done through four tools, called, National Environmental Methods Index (NEMI), Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE). Also, a white assessment was performed using RGB model. The proposed methods could offer an economic alternative for the routine analysis of bulk materials and combined veterinary dosage form.
Graphical Abstract
Eggshell calcified hydrocele sac: a case report
Authors: Molla Yohannis Derbew , Mekonnen Desyibelew Chanie , Gebrehiwot Cheru Lilay , Tadesse Amanuel Kassa , Abera Samuel Addisu , Temeche Lidetu 
Published: August 2023

Abstract
Introduction
Hydrocele, an abnormal fluid collection between parietal and visceral layers of the tunica vaginalis, is the commonest cause of scrotal swelling, and it affects all age groups. Calcification of hydrocele sac/wall is a rare clinical entity. The etiology of calcification of hydrocele sac is not clear, but most literature proposes that calcification is secondary to chronic irritation. Trauma and infectious diseases including Schistosoma haematobium, filariasis, and tuberculosis can also cause calcification of the hydrocele sac.

Case presentation
A 74-year-old Ethiopian male patient presented with left side scrotal swelling of 3 years duration, which was initially small but progressively increased. He had no history of trauma, and he had no history of swelling on the contralateral side. Scrotal ultrasound (US) showed a large echodebrinous left-side scrotal collection with calcifications, bilateral testis appear normal in size, echogenicity, and color Doppler flow with the index of likely chronic hematocele. Therefore, with a diagnosis of left-sided calcified hydrocele, the patient was operated on and the calcified sac was excised and sent for histopathology. Finally, the patient was discharged improved after 2 days of hospital stay.

Conclusion
Calcification of the tunica vaginalis is very rare and is probably due to chronic irritation of the wall from the coexisting hydrocele. Surgical excision of calcified hydrocele sac is the treatment of choice.
Glycemic index, glycemic load, dietary insulin index, and dietary insulin load in relation to cardiometabolic risk factors among participants with atherosclerosis: a cross-sectional study
Authors: Behbahani Hossein Bavi , Shokuhi Mahshad , Clark Cain C. T. , Javid Ahmad Zare , Aghamohammadi Vahideh , bazyar Hadi , Samadani Mahsa , Haybar Habib 
Published: August 2023

Abstract
Background
We examined the cross-sectional associations of dietary Glycemic Index (GI), Glycemic Load (GL), Dietary Insulin Index (DII), and Dietary Insulin Load (DIL) with cardiovascular disease (CVD) factors in subjects with atherosclerosis.

Methods
The present cross-sectional study was conducted on subjects with atherosclerosis. Regular dietary intake was assessed using a 168-item semi-quantitative food frequency questionnaire (FFQ) and GI, GL, DIL, and DII were also calculated. Odds Ratio (OR) and 95% Confidence Intervals (CIs) were estimated for general and central obesity according to the GI, GL, DII, and DIL.

Results
According to the continuous score of GL, there was a significant positive association between GL and central obesity for women in all models. Regarding the association between DIL score and biochemical variables, there was a significant positive association between Na and Aspartate transaminase (AST) with DII. Moreover, there was a significant positive association between LDL-c(p = 0.03) and AST (p = 0.04)with DIL score in all 3 models.

Conclusion
In this study, GL was associated with greater odds of central obesity in women, but not in men. Neither dietary DII nor DIL was associated with BMI and central obesity. GI, GL, DII, and DIL were significantly associated with some CVD risk biomarkers in subjects with atherosclerosis.
In vivo tracking of adenoviral-transduced iron oxide-labeled bone marrow-derived dendritic cells using magnetic particle imaging
Authors: Fink Corby , Gevaert Julia J. , Barrett John W. , Dikeakos Jimmy D. , Foster Paula J. , Dekaban Gregory A. 
Published: August 2023

Abstract
Background
Despite widespread study of dendritic cell (DC)-based cancer immunotherapies, the in vivo postinjection fate of DC remains largely unknown. Due in part to a lack of quantifiable imaging modalities, this is troubling as the amount of DC migration to secondary lymphoid organs correlates with therapeutic efficacy. Magnetic particle imaging (MPI) has emerged as a suitable modality to quantify in vivo migration of superparamagnetic iron oxide (SPIO)-labeled DC. Herein, we describe a popliteal lymph node (pLN)-focused MPI scan to quantify DC in vivo migration accurately and consistently.

Methods
Adenovirus (Ad)-transduced SPIO+ (Ad SPIO+) and SPIO+ C57BL/6 bone marrow-derived DC were generated and assessed for viability and phenotype, then fluorescently labeled and injected into mouse hind footpads (n = 6). Two days later, in vivo DC migration was quantified using whole animal, pLN-focused, and ex vivo pLN MPI scans.

Results
No significant differences in viability, phenotype and in vivo pLN migration were noted for Ad SPIO+ and SPIO+ DC. Day 2 pLN-focused MPI quantified DC migration in all instances while whole animal MPI only quantified pLN migration in 75% of cases. Ex vivo MPI and fluorescence microscopy confirmed that pLN MPI signal was due to originally injected Ad SPIO+ and SPIO+ DC.

Conclusion
We overcame a reported limitation of MPI by using a pLN-focused MPI scan to quantify pLN-migrated Ad SPIO+ and SPIO+ DC in 100% of cases and detected as few as 1000 DC (4.4 ng Fe) in vivo. MPI is a suitable preclinical imaging modality to assess DC-based cancer immunotherapeutic efficacy.

Relevance statement
Tracking the in vivo fate of DC using noninvasive quantifiable magnetic particle imaging can potentially serve as a surrogate marker of therapeutic effectiveness.

Key points
• Adenoviral-transduced and iron oxide-labeled dendritic cells are in vivo migration competent.
• Magnetic particle imaging is a suitable modality to quantify in vivo dendritic cell migration.
• Magnetic particle imaging focused field of view overcomes dynamic range limitation.

Graphical Abstract