bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model
Authors: van Gogh Merel , Glaus Garzon Jesus F. , Sahin Dilara , Knopfova Lucia , Benes Petr , Boyman Onur , Jurisica Igor , Borsig Lubor 
Published: July 2023

Abstract
The transcription factor c-Myb is overexpressed in many different types of solid tumors, including colorectal cancer. However, its exact role in tumorigenesis is unclear. In this study, we show that tumor-intrinsic c-Myb expression in mouse models of colon cancer and melanoma suppresses tumor growth. Although no differences in proliferation, apoptosis, and angiogenesis of tumors were evident in tumors with distinct levels of c-Myb expression, we observed changes in intratumoral immune cell infiltrates. MC38 tumors with upregulated c-Myb expression showed increased numbers of CD103+ dendritic cells and eosinophils, but decreased tumor-associated macrophages (TAM). Concomitantly, an increase in the number of activated cytotoxic CD8+ T cells upon c-Myb upregulation was observed, which correlated with a pro-inflammatory tumor microenvironment and increased numbers of M1 polarized TAMs. Mechanistically, c-Myb upregulation in immunogenic MC38 colon cancer cells resulted in enhanced expression of immunomodulatory genes, including those encoding β2-microglobulin and IFNβ, and decreased expression of the gene encoding the chemokine receptor CCR2. The increased numbers of activated cytotoxic CD8+ T cells contributed to tumor growth attenuation. In poorly immunogenic CT26, LLC, and B16-BL6 tumor cells, c-Myb upregulation did not affect the immunomodulatory gene expression. Despite this, c-Myb upregulation led to reduced B16-BL6 tumor growth but it did not affect tumor growth of CT26 and LLC tumors. Altogether, we postulate that c-Myb functions as a tumor suppressor in a tumor cell–type specific manner and modulates antitumor immunity.
Seasonal Modulation of the Madden–Julian Oscillation’s Impact on Rainfall in Sri Lanka
Authors: Yasanayake Chanud N. , Zaitchik Benjamin F. , Gnanadesikan Anand 
Published: July 2023

Abstract
For the tropical country of Sri Lanka, subseasonal variability in precipitation is both ecologically and societally relevant, influencing agricultural yields, natural hazard risk, energy production, and disease incidence. The primary driver of this subseasonal precipitation variability is the Madden–Julian oscillation (MJO). Here we investigate this influence on Sri Lankan precipitation across seasons, describing MJO-associated precipitation patterns and exploring the potential for MJO-informed subseasonal forecasts. We do so using 40-yr satellite-derived records of precipitation with high spatial resolution (from CHIRPS v2.0) and related meteorological and atmospheric fields (from ERA5 and MERRA-2). We find a direct MJO influence on precipitation corresponding to propagation of the MJO’s convectively active region and suppressed region near Sri Lanka, with the strength and spatial patterns of this influence differing across seasons. There are particularly strong impacts in the second intermonsoon (SIM; October–November) and southwest monsoon (SWM; May–September) seasons. During SIM the impacts are island-wide, but strongest in the northeast. During the SWM the absolute impacts are localized to the southwest, but the relative impacts (i.e., relative to precipitation climatology) are fairly uniform across the island. Moreover, we find significant associations between MJO phase and Sri Lankan precipitation at time scales of up to several weeks. Notably, these associations are stronger when using the OLR-based MJO index (OMI) rather than the more commonly used real-time multivariate MJO index (RMM). While the MJO associations we describe here arise from a highly simplified forecasting scheme, they provide a foundation and impetus for developing a more complete, MJO-informed precipitation forecast method.

Significance Statement
Rainfall variability at the subseasonal (weeks–months) time scale is critical to societal well-being, given its fundamental importance for agriculture, flood risk, hydropower generation, and disease incidence. Our work describes how such rainfall variability in Sri Lanka is impacted by the Madden–Julian oscillation, in which a region of enhanced rainfall and cloudiness, paired with a region of decreased rainfall and cloudiness, circles the globe every 30–60 days. Our results suggest that its influence on Sri Lankan rainfall may be strong enough that incorporating knowledge of the Madden–Julian oscillation into forecasts can improve the accuracy of rainfall prediction for Sri Lanka. Future work should develop a more comprehensive forecast method to assess viability in real-world forecasting scenarios.
The impact of psychological resilience on chronic patients’ depression during the dynamic Zero-COVID policy: the mediating role of stigma and the moderating role of sleep quality
Authors: Mei Yujin , Yang Xue , Liu Changjun , Li Yuqing , Gui Jiaofeng , Zhang Lin 
Published: July 2023

Abstract
Objective
Chronic patients are experiencing depression caused by themselves or the surrounding environment, how to cope with the change of mentality and adjust the psychological stress response, especially under the background of the current dynamic Zero-COVID policy in China, is a problem worth further discussion. The researchers constructed a mediating regulation model to test the influence of psychological resilience on depression of chronic patients during dynamic Zero-COVID, as well as the mediating role of stigma and the moderating role of sleep.

Method
From October 2021 to February 2022, this study used a multi-stage sampling method and random number table method to collect data in the Shang Cheng District of Hangzhou City, Zhejiang Province. Firstly, the Second Affiliated Hospital of the Zhejiang University School of Medicine, a third-class hospital was randomly selected from the Shang Cheng District. Secondly, three departments were strategically selected from this hospital: endocrinology, dermatology, and traditional Chinese medicine. Thirdly, survey points were set up in each department, and chronic patients were strategically selected for questionnaire surveys. Finally, a face-to-face survey was conducted on 398 chronic patients who met the criteria for inclusion. In addition, chronic medical illness burden was assessed using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G), psychological resilience was measured by the Conner-Davidson Resilience Scale (CD-RISC), stigma was measured by the Stigma Scale for Chronic Illness (SSCI), sleep was measured by the Pittsburgh Sleep Quality Index(PSQI) and depression was estimated by the Patient Health Questionaire-9(PHQ-9). SPSS (version 25.0) and PROCESS (version 4.0) were used for correlation analysis, mediation analysis, and mediated moderation analysis.

Results
Psychological resilience was negatively correlated with depression, stigma, and sleep. Depression was positively correlated with stigma and sleep. Stigma and sleep were positively correlated; Stigma played a mediating role in the relationship between psychological resilience and depression; Sleep moderated the first half of the pathway “psychological resilience $$\to$$ stigma $$\to$$ depression”.

Conclusion
Psychological resilience affected depression directly and indirectly through stigma. At the same time, sleep played a moderating role between psychological resilience and depression. The correlation between psychological resilience and stigma was stronger when levels of sleep levels were higher.
Variation in responses to photoperiods and temperatures in Japanese medaka from different latitudes
Authors: Shinomiya Ai , Adachi Daisuke , Shimmura Tsuyoshi , Tanikawa Miki , Hiramatsu Naoshi , Ijiri Shigeho , Naruse Kiyoshi , Sakaizumi Mitsuru , Yoshimura Takashi 
Published: July 2023

AbstractSeasonal changes are more robust and dynamic at higher latitudes than at lower latitudes, and animals sense seasonal changes in the environment and alter their physiology and behavior to better adapt to harsh winter conditions. However, the genetic basis for sensing seasonal changes, including the photoperiod and temperature, remains unclear. Medaka (Oryzias latipes species complex), widely distributed from subtropical to cool-temperate regions throughout the Japanese archipelago, provides an excellent model to tackle this subject. In this study, we examined the critical photoperiods and critical temperatures required for seasonal gonadal development in female medaka from local populations at various latitudes. Intraspecific differences in critical photoperiods and temperatures were detected, demonstrating that these differences were genetically controlled. Most medaka populations could perceive the difference between photoperiods for at least 1 h. Populations in the Northern Japanese group required 14 h of light in a 24 h photoperiod to develop their ovaries, whereas ovaries from the Southern Japanese group developed under 13 h of light. Additionally, Miyazaki and Ginoza populations from lower latitudes were able to spawn under short-day conditions of 11 and 10 h of light, respectively. Investigation of the critical temperature demonstrated that the Higashidori population, the population from the northernmost region of medaka habitats, had a critical temperature of over 18 °C, which was the highest critical temperature among the populations examined. The Miyazaki and the Ginoza populations, in contrast, were found to have critical temperatures under 14 °C. When we conducted a transplant experiment in a high-latitudinal environment using medaka populations with different seasonal responses, the population from higher latitudes, which had a longer critical photoperiod and a higher critical temperature, showed a slower reproductive onset but quickly reached a peak of ovarian size. The current findings show that low latitudinal populations are less responsive to photoperiodic and temperature changes, implying that variations in this responsiveness can alter seasonal timing of reproduction and change fitness to natural environments with varying harshnesses of seasonal changes. Local medaka populations will contribute to elucidating the genetic basis of seasonal time perception and adaptation to environmental changes.
Evaluation of vitamin A and E deficiency with severity of SARS-COV-2 disease: a case–control study
Authors: Mandour Iman Atef , Hussein Sabah Ahmed , Hanna Hany William Z. , Abdellatif Salma Ahmed , Fahmy Balsam Sherif 
Published: July 2023

Abstract
Background
Coronavirus disease 2019 can cause severe inflammation and damage to the lungs. Vitamins A and E are essential in the enhancement of immunity and they tend to decrease in cases with inflammation. Determination of serum levels of vitamins A and E in COVID-19 patients was the aim of the study.

Methods
This case–control study was carried out on 30 ICU–admitted SARS-CoV-2–infected individuals (group A), 30 ward–admitted SARS-CoV-2–infected individuals (group B) and 30 healthy controls (group C). High-performance liquid chromatography was used to measure vitamin A and E levels.

Results
Median levels of vitamin A in group A [0.16 (0.08–0.23) µg/ml] were significantly lower than those in group B [0.4 (0.15–0.65) µg/ml] and in group C [0.81 (0.70–1.16) µg/ml] with P value < 0.001, while there was no significant difference between groups concerning vitamin E levels (P value = 0.535). Vitamin A deficiency showed significant correlation with lower hemoglobin levels, lower platelet counts, higher total leucocyte counts, higher C- reactive protein levels, and higher D-dimer levels. ROC curve construction showed that vitamin A level with cut off < 0.65 µg/ml increases risk of acute respiratory distress syndrome (ARDS) development with sensitivity 90% and specificity 83.3%. Logistic regression analysis showed that cases with vitamin A levels < 0.65 µg/ml were more prone to develop ARDS (OR = 0.003 [0.000–0.036] P < 0.001).

Conclusion
Levels of vitamin A were reduced in COVID-19 patients particularly in ICU–admitted cases. This ensures the association of decreased vitamin A with disease morbidity and the importance of vitamin A supplementation as part of disease management.

Trial registration
Clinicaltrial.gov, NCT05946499. Registered 12 July 2023—Retrospectively registered.
https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000DGLS&selectaction=Edit&uid=U00070DC&ts=2&cx=gieusm.
Effectiveness of neutral honey as a tissue fixative in histopathology
Authors: Alwahaibi Nasar , Al Dhahli Buthaina , Al Issaei Halima , Al Wahaibi Loai , Al Sinawi Shadia 
Published: July 2023

Background: In routine histopathology, 10% neutral buffered formalin (NBF) is the choice fixative. However, formalin is a human carcinogen, so there is a necessity for a safer alternative. To the best of our knowledge, neutral honey, where the pH is around seven, not natural or artificial honey, has not been tested to fix histological samples. This study determined the effectiveness of neutral buffered honey and other types of fixatives to fix histological tissues. Methods: The study was conducted between July 2019 and August 2020 at Sultan Qaboos University, Oman. Sections from three rat livers, kidneys, and stomach tissues were fixed with 10% NBF, neutral buffered Sumer honey (dwarf honey bee), neutral buffered date honey, formalin, Sumer honey, date honey, alcoholic formalin, alcoholic Sumer honey, and alcoholic date honey for 24 hours. Samples were stained with hematoxylin and eosin (H&E), special stains, and vimentin methods. Three expert biomedical scientists then evaluated the fixed and stained samples for the quality of all sections. The fixation ability of the different honey solutions was then compared to 10% NBF and the utility was determined using nuclear and cytoplasmic criteria, specificity, and intensity. Results: H&E showed adequate nuclear staining in all groups compared to 10% NBF. The specificity and intensity of all groups for the Periodic acid–Schiff method were identical to 10% NBF except for Sumer honey and alcoholic date honey. Vimentin showed comparable findings with 10% NBF as there were no significant differences. Conclusions: The findings of this study encourage the use of honey, including neutral, as a possible safe substitute fixative for formalin, however, further experiments on larger specimens should be conducted.
A feasibility randomized controlled superiority trial of fluticasone-vilanterol once daily use for the treatment of mild asthma in adults
Authors: Jassim Ghufran , Morcos Maria , O’Connell Maeve , Cunningham Wayne 
Published: July 2023

Background: The objective of this pilot study is to assess feasibility (recruitment and retention rates) of conducting a definitive randomized controlled trial (RCT) to investigate the effectiveness of fluticasone-vilanterol (Long-acting beta agonist+ Inhaled corticosteroids; LABA+ICS) in the management of mild asthma in adults, compared with usual care. Methods: In this 8-month parallel two-arm pilot trial we randomly assigned 18 patients with mild asthma in a 1:1 ratio to the treatment (n=10) or usual care (n=8) arms. The treatment group received daily LABA+ICS therapy while the usual care group continued as required SABA or SABA+ICS combination. The main outcome measures were descriptors of study feasibility. Secondary outcomes were asthma control score, quality of life, and the number of asthma exacerbations. Results: The baseline characteristics of participants did not differ significantly across the two arms at the start of the trial. Because of slow recruitment and limited funding, the study didn’t meet our recruitment target but did successfully meet our retention criteria. At 32 weeks, analysis indicated significant improvement in asthma control scores in the intervention arm (1.31 vs 2.91; 95% CI [0.72, 2.44]; P-value=0.003), but no significant differences were noted in quality-of-life scores (P-value=0.197). There were no significant differences in post-intervention asthma control mean score (P-value=0.361) or QoL mean score (P-value=0.337) between the two arms after adjustment for pre-intervention scores. Conclusions: This pilot RCT indicates that a definitive RCT is feasible in a primary health care setting. We recommend increasing the recruitment rate by relaxing eligibility criteria, extending the timeline, and increasing the number of sites for recruitment. ClincialTrials.gov registration: NCT04265105 (11/02/2020)
Internal medicine intern performance on the gastrointestinal physical exam
Authors: Gips Julia R. , Stein Ariella Apfel , Luckin Joyce , Garibaldi Brian T. 
Published: July 2023

Abstract

Objectives
The gastrointestinal (GI) physical exam provides critical information about underlying disease states. However, since assessment of physical examination skills is rarely conducted as part of internal medicine residency training, little is known about resident performance on the GI physical exam.

Methods
During a clinical skills assessment that took place between November 2019 and February 2020, internal medicine interns examined the same patient with chronic liver disease while being observed by faculty preceptors. We compared the exam maneuvers performed with those expected by the faculty evaluators. We noted which maneuvers were performed incorrectly, whether physical exam technique correlated with identification of physical exam findings, and if performance on the physical exam was associated with building an appropriate differential diagnosis. This four-hour assessment was required for internal medicine interns within two different residency programs in the Baltimore area.

Results
More than half of the 29 participating interns (n=17, 58.6 %) received a “needs improvement” score on their physical exam technique. Technique was highly correlated with identifying the correct physical signs (r=0.88, p<0.0001). The most commonly excluded maneuvers were assessing for splenomegaly and hepatomegaly. The most commonly missed findings were splenomegaly and hepatomegaly. Most interns included chronic liver disease as part of their differential diagnosis even if they received “needs improvement” scores on physical exam technique or identifying physical signs.

Conclusions
Internal medicine interns would benefit from learning an organized approach to the gastrointestinal exam. This would likely lead to increased identification of important gastrointestinal findings.
Dysfunctional Coupling of Cerebral Blood Flow and Susceptibility Value in the Bilateral Hippocampus is Associated with Cognitive Decline in Nondialysis Patients with CKD
Authors: Wang Hao , Liu Xu , Song Lijun , Yang Wenbo , Li Mingan , Chen Qian , Lv Han , Zhao Pengfei , Yang Zhenghan , Liu Wenhu , Wang Zhen-chang 
Published: July 2023

Significance Statement
Patients with end stage CKD often develop cognitive decline, but whether this is related to the underlying disease or to hemodialysis remains unclear. We performed three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping prospectively in 40 patients with stage 1–4 CKD, 47 nondialysis patients with stage 5 CKD, and 44 healthy controls. Our magnetic resonance imaging data demonstrate that changes in cerebral blood flow–susceptibility coupling might underlie this cognitive decline, perhaps in the hippocampus and thalamus. These results suggest that magnetic resonance imaging parameters are potential biomarkers of cognitive decline in patients with CKD. Moreover, our findings may lead to discovery of novel therapeutic targets to prevent cognitive decline in patients with CKD.

Background
Cerebral blood flow (CBF) and susceptibility values reflect vascular and iron metabolism, providing mechanistic insights into conditions of health and disease. Nondialysis patients with CKD show a cognitive decline, but the pathophysiological mechanisms underlying this remain unclear.

Methods
Three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping were prospectively performed in 40 patients with stage 1–4 CKD (CKD 1–4), 47 nondialysis patients with stage 5 CKD (CKD 5ND), and 44 healthy controls (HCs). Voxel-based global and regional analyses of CBF, susceptibility values, and vascular-susceptibility coupling were performed. Furthermore, the association between clinical performance and cerebral perfusion and iron deposition was analyzed.

Results
For CBF, patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than HCs. Patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than those with CKD 1–4. The susceptibility values in the hippocampus and thalamus were lower in patients with CKD 5ND than in HCs. Patients with CKD 5ND had higher susceptibility value in the caudate nucleus than those with CKD 1–4. More importantly, patients with CKD 5ND had lower CBF-susceptibility coupling than HCs. In addition, CBF and susceptibility values were significantly associated with clinical performance.

Conclusions
Our findings demonstrate a new neuropathological mechanism in patients with CKD, which leads to regional changes in CBF-susceptibility coupling. These changes are related to cognitive decline, providing potential imaging markers for assessing clinical disability and cognitive decline in these patients.
Lower extremity function and subsequent risk of cardiovascular incidence among the elderly in China: evidence from a nationwide survey
Authors: FENG Shixing , WANG Junqi , LI Hangyu , WANG Tianyi , LIU Jialin , LIANG Yafeng , WANG Ying , LIU Jinmin , HAN Dongran , LIU Yixing 
Published: July 2023

Abstract

Aims
Given that little is known about the effect of lower extremity function (LEF) on cardiovascular disease (CVD) subsequent risk among older adults, the association between LEF and CVD in the older Chinese population was investigated by cross-sectional and longitudinal analysis using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS).
Methods
The sample comprised 4636 participants aged at least 60 years from the CHARLS 2011. LEF was defined according to the short physical performance battery (SPPB) scores lower than 8. CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. A total of 4636 participants were recruited from the CHARLS 2011 and were followed up in 2018.
Results
The prevalence of CVD in total populations, good LEF, normal LEF, and poor LEF individuals were 19.07%, 16.97%, 20.72%, 24.77%, respectively. Poor LEF was associated with CVD in total populations. In the longitudinal analysis, individuals with poor LEF were more likely to have incident CVD than good LEF peers, especially stroke. In CVD components, compared to good LEF, individuals with poor LEF had higher risks of heart disease and stroke, and they had higher risks of newly onset stroke but not newly onset heart disease.
Conclusion
The results suggest the potential usefulness of the short physical performance battery for classifying stroke risk in older Chinese adults, which also suggested that preventing and/or improving lower extremity function may be beneficial for reducing stroke incidence and promoting healthy aging for older adults.