bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential biomarkers for multiple sclerosis stage from targeted proteomics and microRNA sequencing
Authors: Tan Ineke L , Modderman Rutger , Stachurska Anna , Almeida Rodrigo , de Vries Riemer , Heersema Dorothea J , Gacesa Ranko , Wijmenga Cisca , Jonkers Iris H , Meilof Jan F , Withoff Sebo 
Published: June 2024

Abstract
Multiple sclerosis is a chronic demyelinating disease of the central nervous system. There is a need for new circulating biomarkers for multiple sclerosis, in particular, markers that differentiate multiple sclerosis subtypes (relapsing–remitting, secondary progressive and primary progressive multiple sclerosis), as this can help in making treatment decisions. In this study, we explore two classes of potential multiple sclerosis biomarkers—proteins and microRNAs—circulating in the cerebrospinal fluid and serum. Targeted medium-throughput proteomics (92 proteins) and microRNA sequencing were performed on serum samples collected in a cross-sectional case–control cohort (cohort I, controls n = 30, multiple sclerosis n = 75) and a prospective multiple sclerosis cohort (cohort II, n = 93). For cohort I, we also made these measurements in paired cerebrospinal fluid samples. In the cohort I cerebrospinal fluid, we observed differences between multiple sclerosis and controls for 13 proteins, including some previously described to be markers for multiple sclerosis [e.g. CD27, C-X-C motif chemokine 13 (CXCL13) and interleukin-7 (IL7)]. No microRNAs were significantly differentially expressed between multiple sclerosis and controls in the cerebrospinal fluid. In serum, 10 proteins, including angiopoietin-1 receptor (TIE2), and 16 microRNAs were significantly different between relapsing–remitting multiple sclerosis and secondary progressive multiple sclerosis after performing a meta-analysis combining both cohorts. In the prospective part of the study, participants with relapsing–remitting multiple sclerosis were followed for around 3 years, during which time 12 participants converted to secondary progressive multiple sclerosis. In these longitudinally collected serum samples, we observed a peak in granzyme B, A and H proteins around the time of conversion. Single-sample enrichment analysis of serum microRNA profiles revealed that the peak in granzyme B levels around conversion coincides with enrichment for microRNAs that are enriched in CD4+, CD8+ and natural killer cells (e.g. miRNA-150). We identified several proteins and microRNAs in serum that represent potential biomarkers for relapsing–remitting and secondary progressive multiple sclerosis. Conversion to secondary progressive disease is marked by a peak in granzyme B levels and enrichment for immune-related microRNAs. This indicates that specific immune cell-driven processes may contribute to the conversion of relapsing–remitting multiple sclerosis to secondary progressive multiple sclerosis.
The role of genomic disorders in chronic kidney failure of undetermined aetiology ≤50 years
Authors: Granhøj Jeff , Pedersen Katja Venborg , Aagaard Mads Malik , Graakjaer Jesper Aagaard , Lildballe Dorte Launholt , Birn Henrik , Rasmussen Maria 
Published: June 2024

ABSTRACT

Background
Genomic disorders caused by copy number variations (CNVs) are prevalent in patients with kidney disease; however, their contribution to chronic kidney failure (KF) of undetermined aetiology (uKF) is unclear. We screened patients with uKF aged 50 years or younger to establish the prevalence of causative CNVs.

Methods
We enrolled patients with an onset of KF ≤50 years from suspected undetermined aetiology for initial review of medical records to exclude patients with clear-cut clinical or histopathological kidney diagnoses or patients with already established genetic kidney diseases. Next, we performed single nucleotide polymorphism (SNP) array–based CNV screening. All the detected CNVs were systematically classified and evaluated as possible causes of the patient's kidney disease. Patients with CNVs not explaining the kidney phenotype were additionally screened for causal variants in 540 genes using whole-genome sequencing.

Results
We enrolled 172 patients, of whom 123 underwent SNP-array. Pathogenic CNVs corresponding to known genomic disorders were identified in 12 patients (9.8%). The identified genomic disorders provided a causative kidney diagnosis in three patients, all of whom had reached KF by age 18 years. The remaining nine patients had CNVs with unclear kidney disease causality. Subsequently, whole-genome sequencing provided a causative genetic diagnosis in an additional four patients, including two diagnostic sequence variants unrelated to the detected CNVs.

Conclusions
Genomic disorders were prevalent in this cohort with uKF, and causative CNVs were identified in 5 of 123 patients. Further studies combining the analysis of CNVs and sequence variants are needed to clarify the causal role of genomic disorders in kidney disease.
Respiratory acidosis and O2 supply capacity do not affect the acute temperature tolerance of rainbow trout (Oncorhynchus mykiss)
Authors: Montgomery Daniel W , Finlay Jennifer , Simpson Stephen D , Engelhard Georg H , Birchenough Silvana N R , Wilson Rod W 
Published: June 2024

Abstract
The mechanisms that determine the temperature tolerances of fish are poorly understood, creating barriers to disentangle how additional environmental challenges—such as CO2-induced aquatic acidification and fluctuating oxygen availability—may exacerbate vulnerability to a warming climate and extreme heat events. Here, we explored whether two acute exposures (~0.5 hours or ~72 hours) to increased CO2 impact acute temperature tolerance limits in a freshwater fish, rainbow trout (Oncorhynchus mykiss). We separated the potential effects of acute high CO2 exposure on critical thermal maximum (CTmax), caused via either respiratory acidosis (reduced internal pH) or O2 supply capacity (aerobic scope), by exposing rainbow trout to ~1 kPa CO2 (~1% or 10 000 μatm) in combination with normoxia or hyperoxia (~21 or 42 kPa O2, respectively). In normoxia, acute exposure to high CO2 caused a large acidosis in trout (blood pH decreased by 0.43 units), while a combination of hyperoxia and ~1 kPa CO2 increased the aerobic scope of trout by 28%. Despite large changes in blood pH and aerobic scope between treatments, we observed no impacts on the CTmax of trout. Our results suggest that the mechanisms that determine the maximum temperature tolerance of trout are independent of blood acid–base balance or the capacity to deliver O2 to tissues.
Ralstonia solanacearum type III effector RipAF1 mediates plant resistance signaling by ADP-ribosylation of host FBN1
Authors: Wu Wei , Zou Huasong , Zheng Huiying , Chen Xinyu , Luo Xuming , Fan Xiaojing , Zhuo Tao , Miao Weiguo 
Published: June 2024

Abstract
Ralstonia solanacearum (Rso) causes destructive bacterial wilt across a broad range of host plants by delivering a repertoire of type III effectors. In the present study, we determined that the deletion of the type III effector RipAF1 resulted in increased virulence on Nicotiana benthamiana, Solanum lycopersicum, and Capsicum annuum plants. RipAF1 showed ADP-ribosylation activity in vivo and in vitro. Transient overexpression of RipAF1 suppressed jasmonic acid (JA) signaling and induced salicylic acid (SA) signaling. The ADP-ribosylation activity of RipAF1 was essential for JA and SA signaling mediation. Host fibrillin FBN1 was identified as a RipAF1-interactor that is ADP-ribosylated by RipAF1 directly. Most importantly, the ADP-ribosylation of conserved residues of FBN1 contributes to its localization to the plasma membrane and leads to the suppression of JA signaling and induction of SA signaling. We concluded that RipAF1 mediates antagonistic crosstalk between JA and SA signaling pathways by ADP-ribosylation of FBN1.
Celebrating 50-years: the history and future of the International Society of Bone Morphometry
Authors: Scheller Erica L , McDonald Michelle , Andersen Thomas L , Sumner D Rick , Noda Masaki , Erben Reinhold G , Boyce Brendan F , Compston Juliet E , Dempster David W , Takahashi Hideaki E , Malluche Hartmut H , Wronski Thomas J 
Published: June 2024

Abstract
The International Society of Bone Morphometry (ISBM) is dedicated to advancing research, education, and clinical practice for osteoporosis and other bone disorders by developing and improving tools for the quantitative imaging and analysis of bone. Its initial core mission was to promote the proper use of morphometric techniques in bone research and to educate and train clinicians and basic scientists in bone morphometry. This article chronicles the evolution of the ISBM and the history and development of bone morphometric techniques for the past 50-years, starting with workshops on bone morphometry in 1973, to the formal incorporation of the ISBM in 1996, to today. We also provide a framework and vision for the coming decades. This effort was led by ISBM presidents Dr Erica L. Scheller (2022-2024) and Dr Thomas J. Wronski (2009-2012) in collaboration with all other living ISBM presidents. Though the underlying techniques and questions have changed over time, the need for standardization of established tools and discovery of novel approaches for bone morphometry remains a constant. The ISBM fulfills this need by providing a forum for the exchange of ideas, with a philosophy that encourages the open discussion of pitfalls and challenges among clinicians, scientists, and industry partners. This facilitates the rapid development and adaptation of tools to meet emerging demands within the field of bone health at a high level.
The mathematics of Epstein semantics
Authors: Krawczyk Krzysztof A 
Published: June 2024

Abstract
This paper is a mathematical investigation of Epstein semantics. One of the main tools of the present paper is the model-theoretic $\textsf{S}$-set construction introduced in [ 14]. We use it to prove several results: (1) that each Epstein model has uncountably many equivalent Epstein models, (2) that the logic of Epstein models is the $\textsf{S}$-set invariant fragment of $\textsf{CPL}$, (3) that several sets of Epstein models are undefinable, (4) that logics of undefinable sets of relations can be finitely axiomatized. We also use other techniques to prove (5) that there are uncountably many Epstein-incomplete logics and that (6) the logic of Epstein models has the interpolation property.
A systematic review of normal tissue neurovascular unit damage following brain irradiation—Factors affecting damage severity and timing of effects
Authors: Nakkazi Annet , Forster Duncan , Whitfield Gillian A , Dyer Douglas P , Dickie Ben R 
Published: June 2024

Abstract

Background
Radiotherapy is key in the treatment of primary and secondary brain tumors. However, normal tissue is inevitably irradiated, causing toxicity and contributing to cognitive dysfunction. The relative importance of vascular damage to cognitive decline is poorly understood. Here, we systematically review the evidence for radiation-induced damage to the entire neurovascular unit (NVU), particularly focusing on establishing the factors that influence damage severity, and timing and duration of vascular effects relative to effects on neural tissue.

Methods
Using PubMed and Web of Science, we searched preclinical and clinical literature published between January 1, 1970 and December 1, 2022 and evaluated factors influencing NVU damage severity and timing of NVU effects resulting from ionizing radiation.

Results
Seventy-two rodents, 4 canines, 1 rabbit, and 5 human studies met inclusion criteria. Radiation increased blood-brain barrier (BBB) permeability, reduced endothelial cell number and extracellular matrix proteoglycans, reduced tight junction proteins, upregulated cellular adhesion molecule expression, reduced activity of glucose and BBB efflux transporters and activated glial cells. In the brain parenchyma, increased metalloproteinases 2 and 9 levels, demyelination, cell death, and inhibited differentiation were observed. Effects on the vasculature and neural compartment were observed across acute, delayed, and late timepoints, and damage extent was higher with low linear energy transfer radiation, higher doses, lower dose rates, broader beams, and in the presence of a tumor.

Conclusions
Irradiation of normal brain tissue leads to widespread and varied impacts on the NVU. Data indicate that vascular damage is in most cases an early effect that does not quickly resolve. More studies are needed to confirm sequence of damages, and mechanisms that lead to cognitive dysfunction.
A leak K+ channel TWK-40 sustains the rhythmic motor program
Authors: Yue Zhongpu , Li Yi , Yu Bin , Xu Yueqing , Chen Lili , Chitturi Jyothsna , Meng Jun , Wang Ying , Tian Yuhang , Mouridi Sonia El , Zhang Cuntai , Zhen Mei , Boulin Thomas , Gao Shangbang 
Published: June 2024

Abstract
Leak potassium (K+) currents, conducted by two-pore domain K+ (K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2P channels on motor rhythm remains enigmatic. We show here that the K2P TWK-40 contributes to the rhythmic defecation motor program (DMP) in Caenorhabditis elegans. Disrupting TWK-40 suppresses the expulsion defects of nlp-40 and aex-2 mutants. By contrast, a gain-of-function (gf) mutant of twk-40 significantly reduces the expulsion frequency per DMP cycle. In situ whole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of dorsorectal ganglion ventral process B (DVB), an excitatory GABAergic motor neuron that activates expulsion muscle contraction. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+ oscillations exhibit obvious defects in loss-of-function (lf) mutant of twk-40. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca2+ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+ defects in twk-40 mutants. In summary, these findings establish TWK-40 as a crucial neuronal stabilizer of DMP, linking leak K2P channels with rhythmic motor activity.
Giant Graviton Expansions for the Line Operator Index
Authors: Imamura Yosuke 
Published: June 2024

Abstract
We discuss giant graviton expansions for the Schur index of ${\cal N}=4$ $U(N)$ SYM with the insertion of Wilson lines of the fundamental and antifundamental representations. We first propose a double-sum giant graviton expansion and numerically confirm that it correctly reproduces the line operator index. We also find that it reduces to a simple-sum expansion when we treat the index as a Taylor series with respect to a specific fugacity.
Hypoxia‐inducible factor prolyl hydroxylase inhibitor alleviates heatstroke‐induced acute kidney injury by activating BNIP3‐mediated mitophagy
Authors: Wang Ling , Song Yongwei , Zhang Pan , Chen Wenting , Xiao Fei , Zhou Ping , Yang Xuesen , Dai Huanzi 
Published: June 2024

AbstractHypoxia‐induced inflammation and apoptosis are important pathophysiological features of heat stroke‐induced acute kidney injury (HS‐AKI). Hypoxia‐inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF‐prolyl hydroxylase inhibitor (HIF‐PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF‐PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF‐PHI could alleviate HS‐induced mitochondrial damage, inflammation, and apoptosis in renal tubular epithelial cells (RTECs) by enhancing mitophagy in vitro and in vivo. By contrast, mitophagy inhibitors Mdivi‐1, 3‐MA, and Baf‐A1 reversed the renoprotective effects of HIF‐PHI. Mechanistically, HIF‐PHI protects RTECs from inflammation and apoptosis by enhancing Bcl‐2 adenovirus E18 19‐kDa–interacting protein 3 (BNIP3)‐mediated mitophagy, while genetic ablation of BNIP3 attenuated HIF‐PHI‐induced mitophagy and abolished HIF‐PHI‐mediated renal protection. Thus, our results indicated that HIF‐PHI protects renal function by upregulating BNIP3‐mediated mitophagy to improve HS‐induced inflammation and apoptosis of RTECs, suggesting HIF‐PHI as a promising therapeutic agent to treat HS‐AKI.
Intranasal Tapentadol Versus Intravenous Paracetamol for Postoperative Analgesia in Lower Limb Orthopaedic Surgeries Under Spinal Anaesthesia
Authors: Suresh Priyanka , Ningegowda Ravish V. , Ramu Anu 
Published: June 2024

Objective:
We aimed to compare the analgesic effectiveness of intranasal tapentadol nasal spray 44.5 mg and intravenous (IV) paracetamol 1 gm during the postoperative period in patients undergoing lower limb orthopedic surgeries under spinal anesthesia.

Methods:
This prospective, randomized, single-blind clinical trial was carried out in a tertiary care teaching hospital. Patients aged between 18 and 60 years of physical status ASA grade 1–3 were included in the study. Postoperative pain scores were measured using the visual analog scale (VAS) in centimeters (cm) every 12 hours in 37 patients per group. The patients were administered either intranasal tapentadol or IV paracetamol every 6 hours for 72 hours, beginning 3 hours after surgery.

Results:
There was a significant group by intervention effect favoring intranasal tapentadol, suggesting a greater reduction in VAS pain scores after the intervention at 72 hours (estimate: −1.58 cm; SE:0.2; P<0.001). Group by time effect for all the measured time frames, except for 36 hours, favored intranasal tapentadol with estimated values for greater reduction in VAS pain scores ranging from −0.8 cm to −1.6 cm.

Discussion:
The results of the present study suggests that intranasal tapentadol results in a greater reduction of postoperative pain compared with IV paracetamol in lower limb orthopedic surgeries. The ease of administration of tapentadol may make it a preferred option over IV paracetamol in such surgeries.
Computed Tomography–Guided Dorsal Root Ganglion Ozone Injection Combined With Pulsed Radiofrequency for Acute Herpes Zoster Neuralgia Treatment of Middle-aged and Elderly People
Authors: Wang Ruxiang , Xia Zhangtian , Ma Ying , Huang Bing , Yao Ming , Ma Ling 
Published: June 2024

Objectives:
To investigate the efficacy and safety of pulsed radiofrequency of the dorsal root ganglion combined with ozone injection for treating acute herpes zoster (HZ) neuralgia in middle-aged and elderly adults.

Methods:
A total of 164 middle-aged and elderly patients with acute HZ were randomly assigned to 2 groups: the pulsed radiofrequency combined with ozone injection group (group A) and the pulsed radiofrequency group (group B). The therapeutic effects were evaluated using Numeric Rating Scale (NRS) scores and the average doses of gabapentin (mg/d) preoperatively and 1 day, 2 weeks, 4 weeks, 12 weeks, and 24 weeks postoperatively. The incidence of clinically significant postherpetic neuralgia (PHN) and complications in the 2 groups were recorded.

Results:
The data showed that the NRS scores and the doses of gabapentin after treatment were significantly lower when compared with the baseline values in both groups. Compared with group B, the NRS scores and the doses of postoperative gabapentin were significantly lower in group A. The incidence of PHN was significantly lower at weeks 4, 12, and 24 in group A than in group B. No adverse reactions occurred in either of the 2 groups post-treatment.

Conclusions:
The results indicated that ozone injection in the dorsal root ganglion combined with pulsed radiofrequency therapy was more effective in treating acute HZ neuralgia in middle-aged and elderly adults. It provides patients with longer-lasting pain relief, decreased incidence of PHN and the doses of medication, and improved quality of life than with Pulsed Radiofrequency treatment.
Medium Term Outcomes in Palliative Transpedicular Corpectomy with Cement Based Anterior Vertebral Reconstruction Performed for Patients with Spinal Metastasis
Authors: Rizkallah Maroun , Boubez Ghassan , Shen Jesse , Alshakfa Fidaa , Phan Philippe , Truong Van Tri , Phan Duy , Wang Zhi 
Published: June 2024

Study Design:
Retrospective.

Objective:
Assess the outcomes of single stage posterior transpedicular corpectomy with cement-based anterior column support for spinal metastasis at longer follow-ups.

Summary of Background Data:
Life expectancy of cancer patients is constantly increasing. Reliable anterior column reconstruction after posterior corpectomy becomes necessary.

Methods:
In this retrospective monocentric study, patients who underwent posterior transpedicular corpectomy and cement-based anterior reconstruction, with a minimum 6 months follow-up, were included. Ambulatory status and pain visual analog score(PVAS), complication rates and Local Sagittal Cobb angle (LSA) were evaluated preoperatively, postoperatively and at the latest follow-up.

Results:
In total, 253 patients were included, with a mean follow-up of 21 months [6-132] and a median survival of 9 months. Pre-operatively, 202 patients(81%) were ambulant while 47 patients (19%) weren’t. At the latest follow-up, 241 patients (95%) were ambulant while 12 patients(5%) weren’t (P<0.001). Dorsal/lumbar PVAS went from 8.2±2.2 pre-operatively to 5.2(±1.7) post-operatively reaching 3.4±1.9 at the latest follow-up (P<0.001). Mean LSA decreased from 13.2⁰(±5.78) pre-operatively to 6.11⁰(±8.51)(P<0.001) post-operatively and reached 7.56⁰(±7.55) at the latest follow-up(P=0.59). Complications occurred in 39(15.4%) patients. One-third of those were mechanical(rod/screw fracture, cement displacement) needing re-intervention in 4 patients(1.6%).

Conclusions:
The mechanical stability offered by the cement-based anterior reconstruction is maintained during the lifespan of patients operated for the spinal metastasis. Satisfying functional and radiological outcomes observed at the last follow-up show that this lasting, cost sparing, and relatively simple reconstruction technique, is a valid alternative for the costly and more complicated cage-based reconstruction.