bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie 
Published: May 2023

Abstract

Purpose:
To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association.

Experimental Design:
Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2).

Results:
Vitamin D deficiency [25(OH)D &lt;12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank&lt;0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51–0.92) for DFS, 0.57 (0.40–0.80) for OS, and 0.71 (0.52–0.98) for TTR. A U-shaped dose–response pattern was observed for DFS and OS (both Pnonlinearity&lt;0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events.

Conclusions:
Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.
Impairment of Angiogenesis-Driven Clot Resolution Is a Key Event in the Progression to Chronic Thromboembolic Pulmonary Hypertension: Validation in a Novel Rabbit Model
Authors: Quarck Rozenn , Willems Lynn , Tielemans Birger , Stoian Leanda , Ronisz Alicja , Wagenaar Allard , Perros Frédéric , Claessen Guido , Ciarka Agnieszka , Godinas Laurent , Belge Catharina , Jacquemin Marc , Delcroix Marion 
Published: May 2023

Background:
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model.

Methods:
We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry.

Results:
Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1.

Conclusions:
The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH.
R-spondin 3/LGR4 (Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 4) Axis Is a Novel Inflammatory and Neurite Outgrowth Signaling System in the Ischemic Brain in Mice
Authors: Shimamura Munehisa , Hayashi Hiroki , Ju Nan , Yoshida Shota , Baba Satoshi , Sasaki Tsutomu , Mochizuki Hideki , Morishita Ryuichi , Nakagami Hironori 
Published: May 2023

Background:
Although stimulation of Wnt/β-catenin signaling is an important strategy to treat ischemic stroke, its signaling pathway has not been fully clarified yet. Recently, RSPO3 (R-spondin 3)/LGR4 (leucine-rich repeat-containing G protein-coupled receptor 4) signaling has resolved TLR4 (toll-like receptor 4)-induced inflammation in lung injury; however, whether this signal is critical in the ischemic brain remains unknown. Therefore, we investigated the role of RSPO3/LGR4 signaling in the ischemic brain.

Methods:
BALB/c mice were exposed to permanent distal middle cerebral artery and common carotid artery occlusion. Temporal RSPO3 and LGR4 expressions were examined, and the mice were randomly assigned to receive vehicle or recombinant RSPO3. The underlying mechanisms were investigated using microglial cell lines and primary mixed glia-endothelia-neuron and primary neuronal cultures.

Results:

In the ischemic brain, RSPO3 and LGR4 were expressed in endothelial cells and microglia/macrophages and neurons, respectively. Stimulation of RSPO3/LGR4 signaling by recombinant RSPO3 recovered neurological deficits with decreased
Il1β
and
iNOS
mRNA on day 3 and increased
Gap43
on day 9. In cultured cells, LGR4 was expressed in neuron and microglia, whereas RSPO3 promoted nuclear translocation of β-catenin. Neuroprotective effects with reduced expression of inflammatory cytokines were observed in lipopolysaccharide-stimulated glia-endothelium-neuron cultures but not in glutamate-, CoCl
2
-, H
2
O
2
-, or oxygen glucose deprivation-stimulated neuronal cultures, indicating that RSPO3/LGR4 can protect neurons by regulating inflammatory cytokines. LGR4-Fc chimera, which was used to block endogenous RSPO3/LGR4 signaling, increased LPS-induced production of inflammatory cytokines, suggesting that endogenous RSPO3 suppresses inflammation. RSPO3 decreased TLR4-related inflammatory cytokine expression by decreasing TLR4 expression without affecting the M1/M2 phenotype. RSPO3 also inhibited TLR2- and TLR9-induced inflammation but not TLR7-induced inflammation, and promoted neurite outgrowth.

Conclusions:
RSPO3/LGR4 signaling plays a critical role in regulating TLR-induced inflammation and neurite outgrowth in the ischemic brain. Enhancing this signal will be a promising approach for treating ischemic stroke.
Integrated taxonomy of the genus Atlanticus Scudder, 1894 in East China and re-evaluation of morphological characters of eight species (Orthoptera: Tettigoniidae: Tettigoniinae)
Authors: Fang Zhen-Gui , Wu Xue , Liu Yi-Jiao , Wu Shi-Yang , He Zhu-Qing 
Published: May 2023

Abstract
In previous taxonomic studies, identification of Atlanticus species was mainly based on male morphological features, such as cercus, tenth abdominal tergum and subgenital plate. In this study, we systematically revise eight Atlanticus species (61 individuals) in East China. We sequence COI genes of all samples for identification, and compare morphologies and male calling songs. The classification based on male cerci, calling songs, and COI genes is consistent. In contrast, the morphologies of male tenth abdominal tergum and subgenital plate varied among species. In addition, we regard A. jiangyei Liu, Wang & Cheng, 2016 as a junior synonym of A. pieli Tinkham, 1941, and A. helleri Liu, Wang & Cheng, 2016 as a junior synonym of A. kiangsu Ramme, 1939.
The Meaning of Religion and Spirituality in the Lives of Youth
Authors: Rinne Emmi , Räihä Pekka , Kuusisto Arniika , Kallioniemi Arto 
Published: May 2023

Abstract
Amongst the complex changes in youth, religious development is also particularly salient. This paper analyzes what is the meaning of religion in youth and what are the possible stress factors that one might encounter when upholding a religious worldview in today’s world. The participants of this study were 41 grade 9 students (ages 15–16) attending four different Finnish Christian schools. The results reveal that religion plays a significant role in the lives of the youth. Furthermore, personal faith functioned as a resource in multiple ways, enabling the youth to experience their life as meaningful. Moreover, according to the youth, a personal religious worldview enabled them to find hope, comfort and strength in different life situations. However, religion was also experienced as a stress factor causing challenges in life, such as being subjected to bullying and discrimination. Still, even then the youth viewed religion as an essential part of their life.
A Pan–North Pacific Wintertime Surface Air Temperature Pattern Influenced by the SST Anomalies over the Kuroshio and Oyashio Extension
Authors: Che Zhihui , Mu Lin , Zhong Linhao 
Published: May 2023

Abstract
A new wintertime surface air temperature (SAT) pattern, called the Asia–Kuroshio and Oyashio Extension–North America (AKNA) pattern, is identified over the pan–North Pacific region (85°E–85°W, 25°–65°N) based on NCEP reanalysis data. The AKNA pattern is likely to influence the climate of the extratropical area of Asia and North America via two SAT dipoles and has a significant impact on the wintertime extremely cold weather along the eastern coastal regions of East Asia. Simulations using an atmospheric general circulation model indicate that wintertime sea surface temperature anomalies (SSTa) in the Kuroshio and Oyashio Extension (KOE) region can force an equivalent barotropic atmospheric ridge downstream and weaken the Siberian high and Alaska atmospheric ridge, resulting in the formation of the AKNA pattern. This circulation pattern tends to intensify the midlatitude (40°–60°N) westerlies over East Asia, which inhibits the southward invasion of the cold air into southern East Asia. Further diagnostic analysis indicates that the KOE SSTa can modulate the variation of storm track and westerlies by affecting baroclinic instability and eddy–mean flow interaction. Moreover, the KOE SSTa can provide a favorable environment for the development of the local atmospheric ascending motion and secondary circulation across the KOE SSTa, thereby affecting variability of the free atmosphere.

Significance Statement
This study aims to build a connection between the wintertime extratropical climate and the variation of the Kuroshio and Oyashio Extension. This work isolated a new wintertime surface air temperature (SAT) pattern over mid–high-latitude Asia and North America, which explains a considerable proportion of cold extremes over the eastern regions of East Asia. The reanalysis data and model simulations indicate that the temporal variability of the SAT pattern is influenced by the change of sea surface temperature in the Kuroshio and Oyashio Extension. These findings emphasize the important role of midlatitude air–sea interaction in the modulation of the mid–high-latitude climate.
Cloud and Precipitation in Low-Latitude Extratropical Cyclones Conditionally Sorted on CYGNSS Surface Latent and Sensible Heat Fluxes
Authors: Naud Catherine M. , Crespo Juan A. , Posselt Derek J. , Booth James F. 
Published: May 2023

Abstract
Extratropical cyclones are the primary cause of midlatitude winds, precipitation, and clouds. Surface latent and sensible heat fluxes from the ocean impact cyclone intensity, but their role in moisture transport leading to cloud and precipitation is still under investigation. While numerical simulations can help establish such links, evaluating and constraining these simulations require observations. To this end, satellite-based observations of cloud and precipitation in low-latitude extratropical cyclones are examined for four distinct classifications based on the Cyclone Global Navigation Satellite System (CYGNSS) latent and sensible heat fluxes, averaged in the post-cold-frontal or warm-sector areas of the cyclones. Using a cyclone compositing approach, contrasts in cloud and precipitation in strong- versus weak-surface-flux conditions are examined. In the post-cold-frontal region, stronger latent or sensible heat fluxes are associated with lower precipitation rates and higher cloud opacity, indicating more vigorous shallow convection. However, larger sensible heat flux cases display larger cloud fraction, while larger latent heat flux cases exhibit lower cloud fraction, which could indicate differing cloud morphologies. In the comma region of the cyclones, clouds and precipitation depend on both cyclone strength and moisture availability. Consistent with this, larger cloud amount and precipitation are found for strong fluxes in the post-cold-frontal region, and weak or negative sensible heat fluxes, indicative of poleward warm advection, in the warm sector. The strong regional differences in the surface heat flux–cloud and precipitation relationships highlight the need for further investigation into moisture supply and transport in cyclones, while providing guidance for future work.
Neurocognitive Deficits in Recently Diagnosed Young Remitted Bipolar I Disorder and At-Risk Subjects: Potential Endophenotypes?
Authors: Reddy Preethi V. , Bojappen Nandhini , Reddy Rajkumari P. , Arumugham Shyam Sundar , Muralidharan Kesavan 
Published: May 2023

Background: Neurocognitive deficits have been reported consistently in euthymic bipolar disorder (BD) across studies. Endophenotype potential of such deficits have been reported in a few studies. However, data from the Indian subcontinent is sparse, and no studies had a sample (patients and high-risk group) aged 20-25 years, which is the actual risk period for developing BD. We studied cognitive deficits, as a potential endophenotype for BD, in recently diagnosed BD (FEM—first episode mania) in remission, young unaffected first-degree relatives (HR) of patients with BD, and healthy controls (HC). Methods: Cross-sectional study design using convenient sampling was employed. We recruited FEM ( n = 25), HR ( n = 25), and age-matched HC ( n = 25) between 18 and 30 years. All HR subjects were <25 years of age, which is the period of vulnerability for BD. All the groups were screened using MINI Version 6. Neurocognitive assessments were done using the NIMHANS neuropsychology battery. The cognitive domains assessed were processing speed, attention, working memory, executive functions, and visual and verbal memory. Results: The three groups were comparable in age and sex (all P > 0.06). The mean (SD) age of the FEM subjects was 23.7 (3.47) years, and the mean duration of illness was 5.92 (2.94) months. Compared to the HC group, the FEM group performed poorly on multiple cognitive domains (all P < 0.05). Performance of the HR group was comparable to the FEM group, but they showed significantly poorer performance compared to HC on the verbal fluency test—controlled oral word association (COWA, F = 12.36, P = 0.001), and the visual learning and memory test—complex figure test-immediate recall (CFT-IR, F = 8.10 and p = 0.001). Conclusions: Cognition is impaired very early in the course of BD. Visual memory and executive function (verbal fluency) have endophenotypic potential. These findings are particularly important given that the HR group were still within the vulnerable period to develop BD. These findings imply a tremendous potential for early diagnosis and prevention by early interventions in BD.
Effectiveness of Fortified Mid-Day Meal in Reducing Anemia Among School Children in Dhenkanal, Odisha: A Quasi-Experimental Study
Authors: Mohapatra Mrinal Kar , Pradhan Ashirbad , Tiwari Divya , Yunus Shariqua , Patro Binod Kumar , Behera Binod Kumar , Sahu Suchanda , Bhatia Vikas , Bhattacharya Shreeporna , Paithankar Pradnya , Dutta Ambarish 
Published: May 2023

Background: Iron-deficiency anemia among school-aged children is widespread in India. The efficacy of micronutrient and iron fortified school-served meals in reducing iron deficiency anemia has been demonstrated in randomized controlled trials in other parts of the globe. The current study evaluates its effectiveness in real-world Indian settings. Methods: Mid-day-Meal (MDM) programme provides free lunch to students of grades 1 to 8 in all public-funded Indian schools. An implementation research project fortified MDM of all public schools of 4 out of 8 sub-districts (“blocks”) of Dhenkanal district of Odisha state with fortified rice kernel (FRK). All the schools of the other 4 blocks fortified with micronutrient powders (MNP)—both FRK and MNP containing equal amounts of supplementary iron and other micronutrients. Schools of 4 matched blocks of neighboring nonimplementing Angul district served as control. Cross-sectional representative samples of students were drawn from the 3 arms, before and after intervention (n = 1764 and n = 1640 respectively). Pre-post changes in anemia prevalence and hemoglobin levels were estimated in the sampled children using difference-in-difference analysis after controlling for inter-arm differences in socioeconomic status, and iron and deworming tablet consumptions. Results: Factoring in pre-post changes in control and adjusting for potential confounders, the proportion of children without anemia and mean hemoglobin improved by 1.93 (1.38, 2.24, P < .001) times and 0.24 (−0.03, 0.51, P = .083) g/dL in MNP; and 1.63 (1.18, 2.24, P = .002) times and 0.18 (−0.09, 0.45, P = .198) g/dL in FRK arms. Conclusions: Fortified MDM could effectively improve anemia status among Indian school-aged children under real-world conditions.
Effects of electroacupuncture at KI3 and ST36 on the hypothalamic paraventricular nucleus in a rat model of chronic glomerulonephritis
Authors: Su Hang , Wu Haosheng , Wu Shengbing , Zhou Meiqi 
Published: May 2023

Objective: The hypothalamic paraventricular nucleus (PVN) acts as a critical integrating center of endocrine/autonomic responses and regulates visceral functional activities. However, its involvement in electroacupuncture (EA) treatment of chronic glomerulonephritis (CGN) remains unclear. Methods: Over four experiments, we randomized 111 rats into: control, untreated model (CGN) or EA-treated model (CGN + EA) groups, a model group receiving EA after PVN damage (CGN + EA + Lesion) or untreated model groups injected with adeno-associated viral vectors encoding human M4 muscarinic receptor (CGN + hM4D) or enhanced green fluorescent protein (CGN + EGFP). CGN was modeled by intraperitoneal injection of bovine serum albumin for 2 weeks. Rats in the CGN + EA and CGN + EA + Lesion groups received EA at bilateral ST36 and KI3 for 14 days. Urine/serum samples were collected to evaluate inflammatory factors and changes in renal function. Results: EA inhibited the release of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β, and decreased urine protein (PRO), creatinine (Cre) and blood urea nitrogen (BUN) levels. PVN damage influenced the effect of EA on the levels of these parameters. EA appeared to inhibit the firing frequency and spectral energy of PVN neurons. In the viral vector experiment, levels of PRO, Cre, IL-6, IL-1β and TNF-α in the CGN group were increased in CGN versus control groups ( p < 0.0001), decreased in CGN + hM4D versus CGN groups ( p < 0.05) and did not differ between CGN + EGFP and control groups ( p > 0.05). Conclusion: Our findings indicate that EA at ST36 and KI3 improves CGN in this rat model by weakening the activity of PVN neurons, alleviating impairment of renal function impairment and restricting the release of inflammatory factors.
Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs
Authors: Capuano Rocco , Prosperini Luca , Altieri Manuela , Lorefice Lorena , Fantozzi Roberta , Cavalla Paola , Guaschino Clara , Radaelli Marta , Cordioli Cinzia , Nociti Viviana , Boffa Laura , Ragonese Paolo , Di Gregorio Maria , Pinardi Federica , Torri Clerici Valentina , De Luca Giovanna , Gajofatto Alberto , Paolicelli Damiano , Tortorella Carla , Gasperini Claudio , Solaro Claudio , Cocco Eleonora , Bisecco Alvino , Gallo Antonio 
Published: May 2023

Background: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. Objectives: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). Methods: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. Results: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. Conclusion: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.