bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury
Authors: Hossain Iftakher , Mohammadian Mehrbod , Maanpää Henna-Riikka , Takala Riikka S. K. , Tenovuo Olli , van Gils Mark , Hutchinson Peter , Menon David K. , Newcombe Virginia F. , Tallus Jussi , Hirvonen Jussi , Roine Timo , Kurki Timo , Blennow Kaj , Zetterberg Henrik , Posti Jussi P.
Published: August 2023

Background

It is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI.

Methods

Ninety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups.

Results

The levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001—p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found.

Conclusion

In patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.
Effect of cumulative radiation exposure from Coronary catheterization on lung cancer mortality
Authors: Liu Jin , Chen Shiqun , Zhou Yang , Zheng Xueyan , Meng Ruilin , Tan Ning , Liu Yong
Published: August 2023

Background

Coronary catheterization (CC) procedure inevitably exposes patients with cardiovascular disease (CVD) to radiation, while cumulative radiation exposure may lead to higher risk of cancer.

Methods

This multi-center, retrospective study was based on the CC procedure in Cardiorenal ImprovemeNt II cohort (CIN-II, NCT05050877) among five regional central tertiary teaching hospitals in China between 2007 and 2020. Patients without known cancer were stratified according to the times they received CC procedure. Baseline information from their last CC procedure was analyzed. Cox regression and Fine-Gray competing risk models were used to assess the relationship between cumulative radiation exposure from CC procedures and cancer-specific, all-cause and cardiovascular mortality.

Results

Of 136,495 hospitalized survivors without cancer at baseline (mean age: 62.3 ± 11.1 years, 30.9% female), 116,992 patients (85.7%) underwent CC procedure once, 15,184 patients (11.1%) on twice, and 4,319 patients (3.2%) underwent CC procedure more than three times. During the median follow-up of 4.7 years (IQR: 2.5 to 7.4), totally 18,656 patients (13.7%) died after discharge, of which 617 (0.5%) died of lung cancer. Compared with the patients who underwent CC procedure once, the risk of lung cancer mortality increased significantly with the increase of the number of CC procedure (CC 2 times vs. 1 time: HR 1.42, 95% CI 1.13 to 1.78, P < 0.001; CC ≥ 3 times vs. 1 time: HR 1.64, 95%CI 1.13 to 2.39, P < 0.05). Similar results were observed in all-cause mortality and cardiovascular mortality, but not in other cancer-specific mortality.

Conclusions

Our data suggest that substantial proportion of CVD patients are exposed to multiple high levels of low-dose ionizing radiation from CC procedure, which is associated with an increased risk of cancer mortality in this population.

Trial registration

ClinicalTrials.gov: NCT05050877; URL:http://www.clinicaltrials.gov; 21/09/2021.
Veterinary deworming agent-induced toxic optic neuropathy: a case report
Authors: Qin Lin , Wang Kan , Ou Yang , Pang Long
Published: August 2023

Background

Veterinary antiparasitic drugs are widely used in countries and regions in which parasitic diseases are endemic, which leads to the risk of accidental ingestion and poisoning in humans. 

Case presentation

A 40-year-old male patient with a history of cirrhosis sought medical attention on November 25, 2021, due to progressive vision loss. He had previously taken triclabendazole and bithionol and was diagnosed with toxic optic neuropathy on examination. Steroid, neurotonic, and high-pressure oxygen therapy were ineffective.

Conclusions

Triclabendazole and bithionol have potential risk of optic neurotoxicity and should be considered for enhanced supervision and warning labels.
Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study
Authors: Wang Chengdong , Zhu Dongdong , Zhang Dongjun , Zuo Xiaowei , Yao Lei , Liu Teng , Ge Xiaodan , He Chenlu , Zhou Yuan , Shen Ziyuan
Published: August 2023

Background

Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings.

Methods

Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results.

Results

After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (β = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (β = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10− 4), and SSC-A on lymphocytes (β = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10− 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10− 3). SCZ also had a causal effect on IgD+ %B cell (β = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10− 4), and DP (CD4+CD8+) %T cell (β = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10− 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10− 5), HLA DR on CD14− CD16− (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10− 5), CD33dim HLA DR+ CD11b− AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10− 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10− 4).

Conclusions

Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.
Exploring negative symptoms heterogeneity in patients diagnosed with schizophrenia and schizoaffective disorder using cluster analysis
Authors: Fekih-Romdhane Feten , Hajje Romy , Haddad Chadia , Hallit Souheil , Azar Jocelyne
Published: August 2023

Background

Dissecting the heterogeneity of schizophrenia may help foster progress in understanding its etiology and lay the groundwork for the development of new treatment options for primary or enduring negative symptoms (NS). In this regard, the present study aimed to: (1) to use cluster analysis to identify subgroups of Lebanese patients diagnosed with either schizophrenia or schizoaffective disorder based on NS clusters, and (2) to relate the statistically-derived subgroups to clinically relevant external validators (including measures if state and trait depression, stigma, insight, loneliness, social support).

Method

A total of 202 adult long-stay, chronic, and clinically remitted patients (166 diagnosed with schizophrenia and 36 with schizoaffective disorder) were enrolled. A cluster analysis approach was adopted to classify patients based on the five NS domains social withdrawal, emotional withdrawal, alogia, avolition and anhedonia.

Results

A three-cluster solution was obtained based on unique NS profiles, and divided patients into (1) low NS (LNS; 42.6%) which characterized by the lowest mean scores in all NS domains, (2) moderate NS (MNS; 25.7%), and (3) high NS (HNS; 31.7%). Post-hoc comparisons showed that depression (state and trait), loneliness and social support could accurately distinguish the schizophrenia subgroups. Additionally, individuals in the HNS cluster had longer duration of illness, longer duration of hospitalization, and were given higher dosages of antipsychotic medication compared to those in the other clusters, but these differences did not achieve the statistical significance.

Conclusion

Findings provide additional support to the categorical model of schizophrenia by confirming the existence of three alternate subtypes based on NS. The determination of distinct NS subgroups within the broad heterogeneous population of people diagnosed with schizophrenia may imply that each subgroup possibly has unique underlying mechanisms and necessitates different treatment approaches.
Waist-to-height ratio associated cardiometabolic risk phenotype in children with overweight/obesity
Authors: Ukegbu Tochi E. , Wylie-Rosett Judith , Groisman-Perelstein Adriana E. , Diamantis Pamela M. , Rieder Jessica , Ginsberg Mindy , Lichtenstein Alice H. , Matthan Nirupa R. , Shankar Viswanathan
Published: August 2023

Background

Childhood overweight/obesity has been associated with an elevated risk of insulin resistance and cardiometabolic disorders. Waist-to-height ratio (WHtR) may be a simple screening tool to quickly identify children at elevated risk for cardiometabolic disorders. The primary objective of the present study was to create sex-specific tertile cut points of WHtR and assess its association with Insulin resistance and elevated liver enzyme concentrations in children, factors using cross-sectional data from the randomized, controlled Family Weight Management Study.

Methods

Baseline data from 360 children (7–12 years, mean Body Mass Index (BMI) ≥ 85th percentile for age and sex) were used to calculate WHtR tertiles by sex, male: ≤ 0.55 (T1), > 0.55- ≤ 0.59 (T2), > 0.59 (T3); female: ≤ 0.56 (T1), > 0.56- ≤ 0.6 (T2), > 0.6 (T3). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to categorize participants as insulin-resistant (HOMA-IR ≥ 2.6) and insulin-sensitive (HOMA-IR < 2.6). Liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were categorized as normal vs. elevated (AST of < 36.0 µkat/L or ≥ 36.0 µkat/L; ALT of < 30.0 µkat/L or ≥ 30.0 µkat/L; ALT > 26 µkat/L males, > 22 µkat/L females). We examined differences in baseline cardiometabolic risk factors by WHtR tertiles and sex-specific multivariable logistic regression models to predict HOMA-IR and elevation of liver enzymes.

Results

Study participants had a mean WHtR of 0.59 ([SD: 0.06]). Irrespective of sex, children in WHtR T3 had higher BMIz scores, blood pressure, triglycerides, 2-h glucose, fasting 2-h insulin, and lower high-density lipoprotein cholesterol (HDL-C) concentrations than those in T2 and T1. After adjusting for covariates, the odds of elevated HOMA-IR (> 2.6) were over five-fold higher among males in T3 versus T1 [OR, 95%CI: 5.83, 2.34–14.52] and T2 [OR, 95%CI: 4.81, 1.94–11.92] and females in T3 [OR, 95%CI: 5.06, 2.10–12.20] versus T1. The odds of elevated ALT values (≥ 30) were 2.9 [95%CI: 1.01–8.41] fold higher among females in T3 compared to T1.

Conclusion

In public health settings, WHtR may be a practical screening tool in pediatric populations to identify children at risk of metabolic syndrome.
Experiences with regular testing of students for SARS-CoV-2 in primary and secondary schools: results from a cross-sectional study in two Norwegian counties, autumn 2021
Authors: Franconeri Léa , Stebbings Sara , Heradstveit Petter , Johansen Mia , Løken Ragnhild , MacDonald Emily , Ødeskaug Liz , Naseer Umaer
Published: August 2023

Background

To allow for normal school attendance during the COVID-19 pandemic, regular testing of students was introduced in the autumn 2021 in Norway to manage COVID-19 transmission. We mapped the experiences of five stakeholders (parents, students, school staff and administration, contact tracing teams) regarding the implementation of regular testing in primary and secondary schools in Oslo and Viken counties, to assess the acceptability through different indicators and improve future guidelines.

Methods

A cross-sectional survey was conducted between October and November 2021 to explore experiences of implementation, compliance, satisfaction, difficulties, concerns, confidence in regular testing, quality of teaching and school attendance. Five stakeholder groups were invited to participate: contact tracing teams; school administrators and employees in primary, lower secondary, and upper-secondary school; students in upper-secondary school and parents of primary and lower secondary students. Bivariate analyses were performed for students, parents, and school employees groups. Descriptive analyses were done for contact tracing teams and school administrators.

Results

Four thousand five hundred sixty-five participants were included in our study. School attendance increased for most of the students in primary and lower secondary schools in Oslo and Viken after the implementation of regular testing. Students across all school levels reported high testing compliance and satisfaction with the implementation. Compliance was significantly associated with an increasing number of weekly tests across all school levels up to two weekly tests. Contact tracing teams were less satisfied with the cooperation with the educational authorities compared to the school employees. Higher educational level of parents was significantly associated with decreased concern of their children getting infected at school after regular testing implementation. Concerned parents were more likely to keep children at home from school, to protect all household members from becoming infected. Lack of time and communication were reported as challenging factors to implementation.

Conclusion

Compliance, satisfaction, and confidence in regular testing of COVID-19 were high among stakeholders. An acceptable testing regime for a future regular testing implementation would be a home-based, bi-weekly test. Increased awareness of the importance of school attendance, safety of regular testing along with good communication and role clarification should be prioritized for stakeholders involved in regular testing.
Chinese critical care certified course in intensive care unit: a nationwide-based analysis
Authors: Li Li , Xu Qianghong , Cai Guolong , Gong Shijin , Liu Dawei , Qiu Haibo , Yu Kaijiang , Chen Dechang , Guan Xiangdong , Yan Jing
Published: August 2023

Background

A training program for intensive care unit (ICU) physicians entitled “Chinese Critical Care Certified Course” (5 C) started in China in 2009, intending to improve the quality of intensive care provision. This study aimed to explore the associations between the 5 C certification of physicians and the quality of intensive care provision in China.

Methods

This nationwide analysis collected data regarding 5 C-certified physicians between 2009 and 2019. Fifteen ICU quality control indicators (three structural, four procedural, and eight outcome-based) were collected from the Chinese National Report on the Services, Quality, and Safety in Medical Care System. Provinces were stratified into three groups based on the cumulative number of 5 C certified physicians per million population.

Results

A total of 20,985 (80.41%) physicians from 3,425 public hospitals in 30 Chinese provinces were 5 C certified. The deep vein thrombosis (DVT) prophylaxis rate in the high 5 C physician-number provinces was significantly higher than in the intermediate 5 C physician-number provinces (67.6% vs. 55.1%, p = 0.043), while ventilator-associated pneumonia (VAP) rate in the low 5 C physician-number provinces was significantly higher than in the high 5 C physician-number provinces (14.9% vs. 8.9%, p = 0.031).

Conclusions

The higher number of 5 C-certified physicians per million population seemed to be associated with higher DVT prophylaxis rates and lower VAP rates in China, suggesting that the 5 C program might have a beneficial impact on the quality of intensive care provision.
The lecturer-tutor in undergraduate medical education; navigating complexity as “a recruiter, a timetabler, an administrator, a counsellor”
Authors: O’Connor Enda , Doyle Evin
Published: August 2023

Background

Tutors play an important role in the delivery of effective undergraduate medical education (UGME). These roles commonly involve competing clinical, educational and research commitments. We sought to obtain a rich description of these posts from doctors working in them.

Methods

We used a pragmatist, sequential explanatory mixed-methods design with a sampling frame of clinical lecturer/tutors in 5 Irish medical schools. Purposive sampling was used for recruitment. Quantitative data collected from a validated online questionnaire were used to inform a semi-structured interview question guide. Thematic analysis was conducted independently by each of the study researchers, using a coding frame derived in part from the findings of the online questionnaire. Quantitative and qualitative mixing occurred during data collection, analysis and reporting.

Results

34 tutors completed the online survey with 7 volunteers for interview. Most respondents took the job to gain experience in either educational practice (79.4%) or in research (61.8%). Major themes to emerge were the diverse interactions with students, balancing multiple professional commitments, a high degree of role-autonomy, mis-perception of role by non-tutor colleagues, challenges around work-life balance and unpredictable work demands. Using a complexity theory lens, the tutor role was defined by its relational interactions with numerous stakeholders, all in the context of an environment that changed regularly and in an unpredictable manner.

Conclusions

The undergraduate tutor works in a demanding role balancing educational and non-educational commitments with suboptimal senior guidance and feedback. The role is notable for its position within a complex adaptive system. An understanding of the system’s interactions recognises the non-linearity of the role. Using a complex systems lens, we propose improvements to undergraduate education centred around the tutor.
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

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

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

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

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

Glycolytic 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

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

In 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

Mathematical 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

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

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

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
Prevalence and correlates of stress, anxiety, and depression in patients with chronic diseases: a cross-sectional study
Authors: M. Swathi , S. Manjusha , Vadakkiniath Isatrin J. , A. Gururaj
Published: August 2023

Background

Many chronic diseases, including diabetes, heart disease, cancer, and respiratory problems, can lead to emotional distress, anxiety, and depression among patients. Likewise, psychological conditions such as anxiety and depression can elevate the risk of developing chronic diseases. The objective of the study was to examine the prevalence of stress, anxiety, and depression in individuals with chronic diseases, as well as to identify the chronic disease with the highest prevalence among all chronic conditions and the factors associated with stress, anxiety, and depression.

Results

In our study, the prevalence rate of stress, anxiety, and depression in patients having chronic diseases was found to be 68.7%, 51.1%, and 58.8%, respectively. The chronic diseases which are included in this study are cardiovascular diseases, metabolic disorders, cancer, respiratory disorders, degenerative disorders, chronic kidney disease, and chronic liver disorders. Among these diseases, cardiovascular disease patients were found to have the highest prevalence of stress, anxiety, and depression. The psychosocial determinants that can trigger stress, anxiety, and depression were analyzed. The factors like age, marital status, primary caretakers of the patient, social isolation, length of hospital stay, social relationships, number of frequent visits to the hospital/month, and the lifestyle of the patient have a significant association with the levels of stress, anxiety, and depression. Factors like monthly income and educational status were also found to be statistically significant with the stress levels, and length of intensive care unit (ICU) stay was significantly associated with the levels of anxiety.

Conclusion

In conclusion, this study found a high prevalence of stress, anxiety, and depression among patients with chronic disease(s). Among all the chronic diseases, cardiovascular disease patients were found to have the highest prevalence of stress, anxiety, and depression. In addition, our study also identified several psychosocial factors that contribute to the development of these mental health conditions which exacerbate the present chronic condition of the patient. These findings highlight the importance of considering the impact of chronic disease on mental health problems.
Low-dose CT radiomics features-based neural networks predict lymphoma types
Authors: Erturk Hasan , Eser Mehmet Bilgin , Buz Yaşar Aysenur , Ayaz Muzaffer , Atalay Basak , Tatoglu Mehmet Tarık , Caymaz Ismail
Published: August 2023

Background

Fluorodeoxyglucose positron emission tomography (PET)–computed tomography (CT) is preferred for pretreatment staging and treatment planning in patients with lymphoma. This study aims to train and validate the neural networks (NN) for predicting lymphoma types using low-dose CT radiomics.

Results

Few radiomics features were stable in intraclass correlation coefficient and coefficient of variation analysis (n = 119). High collinear ones with variance inflation factor were eliminated (n = 56). Twenty-four features were selected with the least absolute shrinkage and selection operator regression for network training. NN had 75.76% predictive accuracy in the validation set and has 0.73 (95% CI 0.55–0.91) area under the curve (AUC) to differentiate Hodgkin lymphoma from non-Hodgkin lymphoma. NN which was used to differentiate B-cell lymphoma from T-cell lymphoma had 78.79% predictive accuracy and has 0.81 (95% CI 0.63–0.99) AUC.

Conclusions

In this study, in which we used low-dose CT images of PET–CT scans, predictions of the neural network were near acceptable lower bound for Hodgkin and non-Hodgkin lymphoma discrimination, and B-cell and T-cell lymphoma differentiation.
Influencing factors of e-learning adoption amongst students in a developing country: the post-pandemic scenario in Bangladesh
Authors: Maisha Kashfia , Shetu Sabakun Naher
Published: August 2023

E-learning is the consequence of the merging of technology and education, and it is now a highly efficient educational medium. Therefore, this study aims to explore the notion of continuous usage of online learning in education. Here, the study examined the key elements influencing whether Bangladeshi university students will continue usage of online learning following the outbreak. It explores a novel setting, extending the UTAUT model and laying the groundwork for upcoming scholars. The UTAUT3 model served as the theoretical foundation for the analysis of the relationship between the components using structural equation modeling. Additionally, this research was conducted as soon as face-to-face education resumed following each pandemic lockdown. According to the study's findings, among the independent variables-performance expectancy, social influence, and behavioral intention were the most important indicators of students' intention to continue use e-learning systems after the COVID-19 pandemic. Moreover, voluntariness of use on social influence was also found to be significant. This is one of the first studies to investigate a new technical service (e-learning services) in the extended framework of UTAUT3 model and gives us an understanding of reasons as to why students keep using e-learning following the epidemic. Furthermore, the findings of the current study provide an innovative perspective for Bangladeshi university administration and policymakers to assess and apply to ensure the successful application of e-learning technologies.