bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mobility group box 1 and a network of other biomolecules influence fatigue in patients with Crohn’s disease
Authors: Kvivik Ingeborg , Grimstad Tore , Bårdsen Kjetil , Jonsson Grete , Kvaløy Jan Terje , Omdal Roald 
Published: June 2023

Abstract
Background
Fatigue is common in patients with chronic inflammatory and autoimmune diseases, often with a severe impact on the patient’s daily life. From a biological point of view, fatigue can be regarded as an element of the sickness behavior response, a coordinated set of responses induced by pathogens to enhance survival during an infection and immunological danger. The mechanisms are not fully understood but involve activation of the innate immune system, with pro-inflammatory cytokines, in particular interleukin (IL)-1β, acting on cerebral neurons. These mechanisms are also active during chronic inflammatory conditions. High mobility group box 1 (HMGB1) protein has interleukin-1 like properties and is a strong inducer of innate immune responses. Its role in generation of fatigue is not clarified. Emerging evidence indicates that also other biomolecules may influence sickness behavior. We aimed to elucidate how HMGB1 influences fatigue in patients with Crohn’s disease, and how the protein interacts with other candidate biomarkers of fatigue.

Methods
In 56 patients with newly diagnosed Crohn’s disease, fatigue was evaluated using three different fatigue instruments: the fatigue visual analog scale (fVAS), Fatigue Severity Scale (FSS), and the vitality subscale of Medical Outcomes Study Short-Form Health Survey (SF-36vs). The biochemical markers IL-1 receptor antagonist (RA), soluble IL-1 receptor type 2 (sIL-RII), heat shock protein 90 alpha (HSP90α), HMGB1, anti-fully reduced (fr)HMGB1 antibodies (abs), hemopexin (HPX), and pigment epithelium-derived factor (PEDF) were measured in plasma. Multivariable regression and principal component analyses (PCA) were applied.

Results
Multivariable regression analyses revealed significant contributions to fatigue severity for HMGB1 in the FSS model, HSP90α in the fVAS model and IL-1RA in the SF-36vs model. Depression and pain scores contributed to all three models. In PCA, two components described 53.3% of the variation. The “inflammation and cellular stress dimension” was dominated by IL-1RA, sIL-1RII, HSP90α, HPX, and PEDF scores, where the “HMGB1 dimension” was dominated by HMGB1, anti-frHMGB1 abs, and fVAS scores.

Conclusion
This study supports the hypothesis that HMGB1 and a network of other biomolecules influence fatigue severity in chronic inflammatory conditions. The well-known association with depression and pain is also acknowledged.
A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA
Authors: Zhao Rui , Yang Zhenming , Zhao Bo , Li Wenjing , Liu Yaohui , Chen Xiaoxue , Cao Jing , Zhang Jiarui , Guo Yan , Xu Licheng , Wang Jinpeng , Sun Yanan , Liu Ming , Tian Linli 
Published: June 2023

Abstract
Background
Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear.

Methods
We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT–PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC.

Results
tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells.

Conclusions
Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.
Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature
Authors: Wisniewski Piotr , McCool Isaac , Walsh John C. , Ausman Chelsea , Edmondson Jenifer , Perry Alexandra , Ewers Evan C. , Maves Ryan C. 
Published: June 2023

Abstract
Background
Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in < 1% of cases. Septic shock is even rarer, with high mortality despite therapy.

Case summary
We describe two cases of coccidioidal septic shock. Both patients were older men of Filipino ancestry presenting with respiratory failure and vasopressor-dependent shock. Antifungal drugs were initiated after failure to improve with empiric antibiotics; in both, Coccidioides was isolated from respiratory cultures. Despite aggressive care, both patients ultimately died of their infections. We provide a review of the published literature on this topic.

Conclusions
Most of the 33 reported cases of coccidioidal septic shock occurred in men (88%) of non-white race and ethnicity (78%). The overall mortality rate was 76%. All survivors received amphotericin B as part of their treatment. Coccidioidomycosis-related septic shock is a rare disease with poor outcomes; delays in diagnosis and treatment are common. Improved diagnostic testing for coccidioidomycosis could enhance recognition of this disease in the future. Although data are limited, early treatment with amphotericin B in cases of coccidioidal septic shock may reduce mortality.
Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants
Authors: Madewell Zachary J. , Yang Yang , Longini Ira M. , Halloran M. Elizabeth , Vespignani Alessandro , Dean Natalie E. 
Published: June 2023

Abstract
Background
The serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9–5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87–5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants.

Methods
This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: (“serial interval” or “generation time”), (“Omicron” or “Delta”), and (“SARS-CoV-2” or “COVID-19”). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported.

Results
There were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3–5.8 days for Delta and 2.1–4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4–4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9–3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8–3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7–3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6–3.1) (three studies).

Conclusions
Serial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.
Light and heavy chain deposition disease with focal amyloid deposition diagnosed with mass spectrometry: a case report
Authors: Shimamoto Yuki , Takahashi Naoki , Katoh Nagaaki , Matsui Yuki , Mochizuki Yusuke , Ito Masanori , Yazaki Masahide , Kametani Fuyuki , Kasuno Kenji , Sekijima Yoshiki , Naiki Hironobu , Iwano Masayuki 
Published: June 2023

Abstract
Background
Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.

Case presentation
We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.

Conclusions
This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.
Fan beam CT-guided online adaptive external radiotherapy of uterine cervical cancer: a dosimetric evaluation
Authors: Peng Haibo , Zhang Jie , Xu Ningyue , Zhou Yangang , Tan Huigang , Ren Tao 
Published: June 2023

Abstract
Purpose
To discuss the dosimetric advantages and reliability of the accurate delivery of online adaptive radiotherapy(online ART) for uterine cervical cancer(UCC).

Methods and materials
Six UCC patients were enrolled in this study. 95% of the planning target volume (PTV) reached 100% of the prescription dose (50.4 Gy/28fractions/6weeks) was required. The patients were scanned with uRT-Linac 506c KV-FBCT then the target volume (TV) and organs at risk (OARs) were delineated by doctors. The dosimeters designed and obtained a routine plan (Plan0). KV-FBCT was used for image guidance before subsequent fractional treatment. The online ART was processed after registration, which acquired a virtual nonadaptive radiotherapy plan (VPlan) and an adaptive plan (APlan). VPlan was the direct calculation of Plan0 on the fractional image, while APlan required adaptive optimization and calculation. In vivo dose monitoring and three-dimensional dose reconstruction were required during the implementation of APlan.

Results
The inter-fractional volumes of the bladder and rectum changed greatly among the treatments. These changes influenced the primary gross tumor volume (GTVp) and the position deviation of GTVp and PTV and positively affected the prescription dose coverage of TV. GTVp decreased gradually along with dose accumulation. The Dmax, D98, D95, D50, and D2 of APlan were superior to those of VPlan in target dose distribution. APlan had good conformal index, homogeneity index and target coverage. The rectum V40 and Dmax, bladder V40, the small bowel V40 and Dmax of APlan were better than that of VPlan. The APlan’s fractional mean γ passing rate was significantly higher than the international standard and the mean γ passing rate of all cases after the three-dimensional reconstruction was higher than 97.0%.

Conclusion
Online ART in external radiotherapy of UCC significantly improved the dose distribution and can become an ideal technology to achieve individualized precise radiotherapy.
Secular trend of non-communicable chronic disease prevalence throughout the life span who endured Chinese Great Famine (1959–1961)
Authors: He Xiaoxue , Shi Xiaojuan , Pan Degong , Wang Huihui , Zhang Xue , Pu Lining , Luo Mingxiu , Li Jiangping 
Published: June 2023

Abstract
Background
Famine is a risk factor for non-communicable chronic diseases (NCDs), which account for over 80% of deaths in China. The effect of famine on the prevalence of NCDs in terms of various age groups, time periods and cohorts is currently poorly understood.

Objective
This study aims to explore long-term trends in the impact of China’s Great Famine (1959–1961) on NCDs in China.

Methods
This study used data from the 2010–2020 China Family Panel Longitudinal Survey across 25 provinces in China. The subjects were aged 18–85 years, and the total number of subjects was 174,894. The prevalence of NCDs was derived from the China Family Panel Studies database (CFPS). An age-period-cohort (APC) model was used to estimate the age, period and cohort effects of NCDs in 2010–2020 and the effect of famine on the risk of NCDs in terms of cohort effects.

Results
The prevalence of NCDs increased with age. Additionally, the prevalence did not clearly decrease over the survey period. Regarding the cohort effect, people born in the years adjacent to the famine period had a higher risk of NCDs; additionally, females, those born in rural areas, and those who lived in provinces with severe famine and post-famine had a higher likelihood of NCDs.

Conclusions
Experiencing famine at an early age or the experience of famine in a close relative’s generation (births after the onset of famine) are associated with an increased risk of NCDs. Additionally, more severe famine is associated with a higher risk of NCDs.
Exploring the effects of health behaviors and mental health on students’ academic achievement: a cross-sectional study on lebanese university students
Authors: Hammoudi Halat Dalal , Hallit Souheil , Younes Samar , AlFikany Mira , Khaled Sanaa , Krayem Maha , El Khatib Sami , Rahal Mohamad 
Published: June 2023

AbstractBackgroundHigh academic achievement, an important determinant of future success, is known to be influenced by many factors including dietary behavior, lifestyle and mental health, among others. The objectives of the current study were to explore university students’ nutritive habits, daily lifestyle, and mental status, and to scrutinize the associations between these factors and students’ academic achievement.MethodsA cross-sectional study was conducted among students of a private Lebanese university, using an electronic survey. Diet, eating habits, physical activity, sleep, and smoking were evaluated, and mental health was assessed using a validated Arabic version of the combined Depression, Anxiety, Stress Score (DASS-8). Academic achievement was measured using the Subjective Academic Achievement Scale (SAAS).ResultsA total of 1677 students participated in the questionnaire. The results of a linear regression taking the SAAS score as the dependent variable, showed that students who have a non-scientific versus scientific major (Beta = 0.53), and having breakfast ≥ 4 days per week compared to less than 2 days (Beta = 0.28) were significantly associated with higher SAAS scores. More psychological distress (Beta = − 0.06) and a higher number of days of eating out (Beta = − 0.07) were significantly associated with lower SAAS scores.ConclusionsThis is the first investigation on a Lebanese university students’ academic success in relation to lifestyle and mental profiles. Better academic achievement was demonstrated by students having healthier dietary and lifestyle habits, as well as less distressing mental status. Such results, in light of the compounded and unprecedented crises with which Lebanon has been assailed, suggest the need to focus on promoting healthy habits among students in higher education as a possible driver of better academic success.
Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
Authors: Chen Ying , Rui Rong , Wang Li , Wang Hao , Zhu Bingbing , Cao Aili 
Published: June 2023

Abstract
Purpose
This study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice.

Methods
Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were served as the control group. These mice received HQD treatment for 8 weeks. After treatment, the kidney function, histopathology, micro-assay, and protein expression levels were assessed.

Results
HQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin excretion, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the of mesangial matrix proliferation, foot process effacement, decreased nephrin expression and reduced number of podocytes. Expression profiling analysis revealed global transcriptional changes that predicted related functions, diseases and pathways. HQD treatment activated protein expressions of BMP2, BMP7, BMPR2, and active-Rap1, while inhibiting Smad1 and phospho-ERK. In addition, HQD was associated with improvements in lipid deposition in the kidneys of db/db mice.

Conclusion
HQD ameliorated the progression of DKD in db/db mice by regulating BMP transcription and downstream targets, inhibiting the phosphorylation of ERK and the expression of Smad1, promoting Rap1 binding to GTP, and regulating the lipid metabolism. These findings provide a potential therapeutic approach for treating DKD.
Differentially expressed chaperone genes reveal a stress response required for unidirectional regeneration in the basal chordate Ciona
Authors: Jeffery William R. , Li Bo , Ng Mandy , Li Lianwei , Gorički Špela , Ma Li 
Published: June 2023

AbstractBackgroundUnidirectional regeneration in the basal chordateCiona intestinalisinvolves the proliferation of adult stem cells residing in the branchial sac vasculature and the migration of progenitor cells to the site of distal injury. However, after theCionabody is bisected, regeneration occurs in the proximal but not in the distal fragments, even if the latter include a part of the branchial sac with stem cells. A transcriptome was sequenced and assembled from the isolated branchial sacs of regenerating animals, and the information was used to provide insights into the absence of regeneration in distal body fragments.ResultsWe identified 1149 differentially expressed genes, which were separated into two major modules by weighted gene correlation network analysis, one consisting of mostly upregulated genes correlated with regeneration and the other consisting of only downregulated genes associated with metabolism and homeostatic processes. Thehsp70,dnaJb4, andbag3genes were among the highest upregulated genes and were predicted to interact in an HSP70 chaperone system. The upregulation of HSP70 chaperone genes was verified and their expression confirmed in BS vasculature cells previously identified as stem and progenitor cells. siRNA-mediated gene knockdown showed thathsp70anddnaJb4,but notbag3,are required for progenitor cell targeting and distal regeneration. However, neitherhsp70nordnaJb4were strongly expressed in the branchial sac vasculature of distal fragments, implying the absence of a stress response. Heat shock treatment of distal body fragments activatedhsp70anddnaJb4expression indicative of a stress response, induced cell proliferation in branchial sac vasculature cells, and promoted distal regeneration.ConclusionsThe chaperone system geneshsp70,dnaJb4, andbag3are significantly upregulated in the branchial sac vasculature following distal injury, defining a stress response that is essential for regeneration. The stress response is absent from distal fragments, but can be induced by a heat shock, which activates cell division in the branchial sac vasculature and promotes distal regeneration. This study demonstrates the importance of a stress response for stem cell activation and regeneration in a basal chordate, which may have implications for understanding the limited regenerative activities in other animals, including vertebrates.
Dopamine modulates the retinal clock through melanopsin-dependent regulation of cholinergic waves during development
Authors: Kinane Chaimaa , Calligaro Hugo , Jandot Antonin , Coutanson Christine , Haddjeri Nasser , Bennis Mohamed , Dkhissi-Benyahya Ouria 
Published: June 2023

Abstract
Background
The mammalian retina contains an autonomous circadian clock that controls various aspects of retinal physiology and function, including dopamine (DA) release by amacrine cells. This neurotransmitter plays a critical role in retina development, visual signalling, and phase resetting of the retinal clock in adulthood. Interestingly, bidirectional regulation between dopaminergic cells and melanopsin-expressing retinal ganglion cells has been demonstrated in the adult and during development. Additionally, the adult melanopsin knockout mouse (Opn4−/−) exhibits a shortening of the endogenous period of the retinal clock. However, whether DA and / or melanopsin influence the retinal clock mechanism during its maturation is still unknown.

Results
Using wild-type Per2Luc and melanopsin knockout (Opn4−/−::Per2Luc) mice at different postnatal stages, we found that the retina generates self-sustained circadian rhythms from postnatal day 5 in both genotypes and that the ability to express these rhythms emerges in the absence of external time cues. Intriguingly, only in wild-type explants, DA supplementation lengthened the endogenous period of the clock during the first week of postnatal development through both D1- and D2-like dopaminergic receptors. Furthermore, the blockade of spontaneous cholinergic retinal waves, which drive DA release in the early developmental stages, shortened the period and reduced the light-induced phase shift of the retinal clock only in wild-type retinas.

Conclusions
These data suggest that DA modulates the molecular core of the clock through melanopsin-dependent regulation of acetylcholine retinal waves, thus offering an unprecedented role of DA and melanopsin in the endogenous functioning and the light response of the retinal clock during development.