bluuebunny/crossref_metadata_2025_split huggingface dataset:
MORF4L2 induces immunosuppressive microenvironment and immunotherapy resistance through GRHL2/MORF4L2/H4K12Ac/CSF1 axis in triple-negative breast cancer
Authors: Sui Xin-Yi , Cao Shuo-Wen , Song Xiao-Qing , Liu Xi-Yu , Chen Chao , Yan Qingya , Wang Zhi-Qing , Zhang Wen-Juan , Ma Lin-Xiaoxi , Jin Xi , Ma Ding , Xiao Yi , Wu Song-Yang , Xu Ying , Shao Zhi-Ming , Fan Lei 
Published: January 2025

Abstract

Background
Although immunotherapy has achieved great progress in advanced triple-negative breast cancer (TNBC), there are still numerous patients who do not benefit from immunotherapy. Therefore, identification of the key molecule that induces immune escape and clarification of its specific mechanism in TNBC are urgently needed.

Methods
In this research, single cell sequencing and bulk sequencing were conducted for biomarker screening. Immunohistochemistry, multiplex immunofluorescence, and orthotopic TNBC tumor model were applied in identifying the key molecule driving immune escape. At the mechanical level, RNA sequencing, in vitro co-culturing system, flow cytometry, Western blotting, ELISA, and real-time qPCR were carried out.

Results
Mortality factor 4 like 2 (MORF4L2) expression is significantly up-regulated among patients who developed anti-PD1 resistance. MORF4L2 enhances anti-PD1 resistance by inducing the chemotaxis of macrophage infiltration and promoting their polarization towards the alternative activation phenotype (M2), thus creating an immunosuppressive microenvironment. Mechanistically, MORF4L2 actes as part of NuA4 histone acetyltransferase (HAT) complex, contributes to to histone 4 lysine 12 acetylation (H4K12Ac) and activates the downstream transcription of macrophage colony-stimulating factor (CSF1). CSF1 is secreted by tumor cells and binds to the macrophage-surface CSF1 receptor (CSF1R), which chemotactically converted and polarized macrophages to the M2 phenotype. Furthermore, we revealed that grainyhead like transcription factor 2 (GRHL2) could promote MORF4L2 transcription by binding to the MORF4L2 enhancer region. Notably, BLZ549, an inhibitor of CSF1R, restored the anti-PD1 sensitivity by blocking the GRHL2/MORF4L2/H4K12Ac/CSF1 axis.

Conclusions
GRHL2/MORF4L2/H4K12Ac/CSF1 axis plays an important role in anti-PD1 resistance. CSF1R inhibitors can reverse GRHL2/MORF4L2-mediated anti-PD1 resistance.
SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis
Authors: Chen Fanghui , Lang Liwei , Yang Jianqiang , Yang Fan , Tang Sijia , Fu Zhenzhen , Saba Nabil F. , Luo Ming , Teng Yong 
Published: January 2025

Abstract
Background
Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.

Methods
The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S. Head and neck squamous cell carcinoma (HNSCC) cell lines and orthotopic mouse models were employed for research. Morphological changes were observed using both light microscopy and transmission electron microscopy. Molecular alterations were analyzed through Western blotting and ELISA kits. The tumor secretome was characterized using a combination of biotinylation and LC-MS analysis. Immune cell changes were evaluated by flow cytometry and immunohistochemistry.

Results
Compared to its parental virus, VSV-S not only increases apoptosis by overexpressing SMAC during VSV infection but also triggers elevated levels of PANoptosis (pyroptosis, apoptosis, and necroptosis) in HNSCC cells via activation of caspase-1/gasdermin D (GSDMD) signaling. As a result, VSV-S-induced PANoptosis promotes CD8+ T cell tumor infiltration and enhances their cytotoxic capacity, eventually potentiating T cell-mediated antitumor immunity. Moreover, VSV-S reduces PDL1 levels in HNSCC cells and, in combination with PD1 blockade, produces a more potent antitumor effect than either therapy alone.

Conclusions
Our findings demonstrate that the combination of VSV-S and PD1 blockade offers a synergistic therapeutic strategy for HNSCC, supporting the advancement of VSV-based virotherapy as a promising strategy to improve outcomes for HNSCC patients.
COping with Rheumatic Stressors (CORS) questionnaire: validated German translation and cross-cultural adaptation for patients with axSpA
Authors: Vaupel Kristina , Kiefer David , Ramiro Sofia , Kiltz Uta , van Lankveld Wim , Hammel Ludwig , Baraliakos Xenofon 
Published: January 2025

Abstract
Background
Patients with Rheumatic and Musculoskeletal Diseases, including axial spondyloarthritis (axSpA), may suffer from stressors like pain and functional impairments leading to limitations in their self-perceived health status. The COping with Rheumatic Stressors (CORS) questionnaire was developed to analyze how patients cope with these stressors. The CORS is currently not available in German.

Objective
First, to translate, cross-culturally adapt and to linguistically validate the original Dutch CORS into German. Second, to test the pre-final German translation through cognitive debriefing in patients with axSpA.

Methodology
The original Dutch CORS underwent a multistep cross-cultural adaptation process, as described by Beaton. It was first independently translated into German by bilingual Dutch-German lay and expert translators. Subsequently, it was translated back from the German version into Dutch. Remaining discrepancies were resolved by a scientific committee, resulting in a pre-final German version. This version was then tested through cognitive debriefing by 10 patients with axSpA across a broad spectrum of sociodemographic backgrounds.

Results
Forward and backward translations of the CORS revealed minor discrepancies, mainly based on the degree of formal versus informal language usage, minor semantic errors or unusual syntax, which led to minor modifications in the wording. Reviewed by the scientific committee, the pre-final consensus German version was linguistically validated by cognitive debriefing by 10 patients with axSpA. Cognitive debriefing confirmed and ensured closest linguistic validity for German in Germany and highest equivalence to the Dutch original version.

Conclusion
The German CORS was shown to have high cross-cultural and face validity for the assessment of coping with rheumatic stressors.
Spontaneous orbital meningoencephalocele and temporal encephalocele: An odd cause of proptosis and seizure, a case report and literature review
Authors: El Graini S. , Retal H. , Habib Chorfa S. , Ech-Cherif El Kettani N. , Fikri M. , Jiddane M. , Touarsa F. 
Published: January 2025

AbstractMeningoencephaloceles (MEC) of the skull base commonly result from head trauma, or congenital malformation, or may arise spontaneously due to increased intracranial pressure, leading to a bony defect and subsequent herniation of brain parenchyma. Spontaneous MEC at orbital and temporal locations are rare, with only a few cases reported in the literature. Brain MRI is typically used for diagnosis, and treatment may be medical or surgical, depending on the size of the bony defect. We present an unusual case of a 69-year-old woman with spontaneous orbital and temporal MEC, resulting in proptosis, strabismus, and seizures secondary to idiopathic intracranial hypertension (IIH). This condition was managed medically, with a favourable outcome. This report aims to describe and analyse the case, reviewing the literature on spontaneous MEC in adult patients at different locations caused by IIH and their management, emphasizing the critical role of imaging in diagnosing this etiology.
Assessment of efficacy and safety of imatinib as an adjunct host-targeted therapy for parasite clearance in chloroquine-resistant malaria: a prospective case control study
Authors: Zubair Ahmed Fazeel , P Shaifulla 
Published: January 2025

Abstract
Overview
Chloroquine-resistant malaria poses a significant treatment challenge, especially in endemic areas. Host-targeted therapies, like tyrosine kinase inhibitors (TKIs) such as imatinib, have shown potential to improve malaria treatment outcomes by disrupting parasite egress from red blood cells. This study investigates the efficacy and safety of imatinib as an adjunct therapy to accelerate fever reduction and parasite clearance in male patients with chloroquine-resistant malaria.

Patients and methods
This open-label, prospective, randomized case–control study was conducted on 60 male patients aged 18–50, diagnosed with chloroquine-resistant malaria at Viswabharathi Medical College, India. Patients were randomized into two groups: a control group receiving standard anti-malarial therapy and a test group receiving standard therapy plus imatinib (400 mg daily for 3 days). Efficacy endpoints included the time to reduce parasite load by half and normalization of body temperature. Safety assessments monitored adverse reactions throughout the treatment period.

Results
The imatinib group demonstrated a significantly faster reduction in fever, with normalization by day 2 compared to day 3 in the control group (p < 0.05). Parasite counts decreased more rapidly in the imatinib group, with mean levels falling to below 1000 parasites/mcl by day 3. Mild adverse effects, primarily headaches and gastrointestinal symptoms, were reported but resolved by day 3 with no severe events directly attributed to imatinib.

Conclusion
Imatinib as an adjunct therapy may enhance the efficacy of standard anti-malarial treatments by accelerating parasite clearance and fever reduction in cases of chloroquine-resistant malaria. These findings support further investigation into TKIs as a complementary approach to existing malaria treatments, particularly in regions facing drug resistance challenges.
Assessing heavy metal contamination in leafy vegetables and associated health risks in Dhaka, Bangladesh
Authors: Hosen Anowar , Jahan Rumana Akther , Simol Hasina Akhter , Huda Muhammad Nurul 
Published: January 2025

Abstract
Leafy vegetables, widely consumed for their nutritional benefits, can pose significant health risks when contaminated with toxic metals, emphasizing the need to monitor and assess their safety. An atomic absorption spectrophotometer (AAS) was used to analyze the metal accumulation in leafy vegetables. The specific minerals analyzed included calcium (Ca), magnesium (Mg), zinc (Zn), manganese (Mn), and iron (Fe). Additionally, heavy metals such as copper (Cu), cadmium (Cd), lead (Pb), chromium (Cr), cobalt (Co), and nickel (Ni) were also examined. Risk factors for the human population were examined, focusing on the transfer of metals from different sources to vegetable samples. These metals were then consumed by humans through the ingestion of leafy vegetables that had accumulated them. The results of this study showed that the average concentrations detected ranged from 68.0 to 1507 mg/kg of Ca, 126.0 to 829.0 mg/kg of Mg, 4.03 to 44.0 mg/kg of Zn, 2.7 to 74.5 mg/kg of Mn, 25.0 to 154.5 mg/kg of Fe, 0.74 to 4.51 mg/kg of Cu, 0.005 to 0.22 mg/kg of Cd, 0.19 to 1.75 mg/kg of Pb, 0.43 to 4.69 mg/kg of Cr, 0.005 to 0.39 mg/kg and 0.25 to 2.21 mg/kg of Ni. The highest mean levels of minerals like Ca, Mg, Zn, Mn and Fe were detected in red amaranth, Garden purslane, Stem amaranth. The study used, estimated daily intakes (EDIs), target hazard quotient (THQ), and cancer risk (CR) assessments to assess the potential health risks of consuming contaminated vegetables. The results showed that the value of THQ was found to be larger than 1 in the cases of Pb and Mn in Stem Amaranth, indicating a significant non-carcinogenic health risk, especially due to high lead exposure exceeding the standard limit by two-fold in all fields. Furthermore, the CR values for Cd, Cr, and Ni indicated a notable carcinogenic risk in multiple cases.
Basal and stimulated inhibin B in pubertal disorders
Authors: Chaudhary Shakun , Walia Rama , Quinton Richard 
Published: January 2025

Abstract
Pubertal disorders in the form of delayed puberty (DP) or precocious puberty (PP) can cause considerable anxiety to both children and parents. Since the clinical and biochemical signatures of self-limiting and permanent conditions overlap considerably, it can be hard to determine whether to offer them reassurance or intervention. Researchers have thus long been searching for a robust test to indicate that the process of endogenous puberty is underway and is likely to proceed to completion. Although existing tests are available, such as basal gonadotropins, gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone, and basal and human chorionic gonadotropin-stimulated testosterone, their diagnostic specificity is inadequate.
Inhibin B, a glycoprotein hormone, is secreted by Sertoli cells in males and small antral follicles in females. The entry into puberty is characterized by a rise in inhibin B levels in both genders. For the past two decades, researchers have been studying the role of inhibin B in the differential diagnosis of DP as well as PP. Initial studies showed promising results for using inhibin B to distinguish between constitutional (or self-limited) DP (SLDP) and congenital hypogonadotropic-hypogonadism (CHH). However, diverse population studies have revealed varying cut-offs, limiting the use of basal inhibin B(basal-iB) in routine clinical practice. Recently, the concept of stimulated inhibin B has been introduced, using either follicle-stimulating hormone (FSH) or GnRH-analogs. Both FSH- and GnRH-analog-stimulated inhibin B concentration were found to be more reliable than basal levels in the investigation of pubertal disorders. This review examines the current status of basal-iB in the differential diagnosis of delayed and precocious puberty, addressing its main advantages and limitations, and shedding light on the role of stimulated inhibin B concentrations.
Treatment of Hyperthyroidism in Graves' Disease Complicated by Thyroid Eye Disease
Authors: Bartalena Luigi , Smith Terry J 
Published: January 2025

Abstract
Thyroid eye disease (TED) is the most consequential extrathyroidal manifestation or complication of Graves' disease (GD). Treatment of hyperthyroidism in GD complicated by TED is challenging. Antithyroid drugs (ATDs) and thyroidectomy do not change the natural course of TED, while radioactive iodine (RAI) is associated with a small but well-documented risk of TED de novo occurrence or its progression/worsening. In the presence of mild TED, any treatment for hyperthyroidism can be used, but should RAI treatment be selected, steroid prophylaxis (short course of low-dose prednisone) is strongly recommended if TED is of recent onset and/or risk factors for progression exist. In moderate to severe and active TED, ATDs are the preferred treatment, but thyroidectomy is a valid option. RAI ablation is generally avoided; it might be used when the clinical situation calls for it, but with extreme caution, if an aggressive treatment for TED with high-dose glucocorticoids (with or without orbital radiotherapy) is administered concomitantly. In moderate to severe and inactive TED, all 3 treatments for hyperthyroidism are acceptable, and steroid prophylaxis in RAI-treated patients should be given when risk factors for TED progression are identified. Management of sight-threatening TED represents the absolute priority, and hyperthyroidism should be controlled with ATDs until TED has been controlled.
Search Strategies
Current guidelines, original articles, clinical trials, systematic reviews, and meta-analyses up to June 2024 were searched using the following terms: “Graves' disease,” “management of Graves' disease,” “antithyroid drugs,” “radioactive iodine,” “thyroidectomy,” “thyroid eye disease,” “Graves' orbitopathy or ophthalmopathy.”
Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia
Authors: Ali Dalal S , Mirza Reza D , Hussein Salma , Alsarraf Farah , Alexander R Todd , Abu Alrob Hajar , Appelman-Dijkstra Natasha M , Biosse-Duplan Martin , Brandi Maria Luisa , Carpenter Thomas O , Chaussain Catherine , Dandurand Karel , Filler Guido , Florenzano Pablo , Fukumoto Seiji , Grasemann Corinna , Imel Erik A , Jan de Beur Suzanne M , Morgante Emmett , Ward Leanne M , Khan Aliya A , Guyatt Gordon 
Published: January 2025

Abstract

Objective
To examine the evidence addressing the management of X-linked hypophosphatemia (XLH) in children to inform treatment recommendations.

Methods
We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included randomized controlled trials (RCTs) and observational studies of individuals younger than 18 years with clinically or genetically confirmed XLH. Manuscripts comparing burosumab to either no treatment or conventional therapy (phosphate and active vitamin D) or evaluating conventional therapy to no treatment were included. Two reviewers independently determined eligibility, extracted data, and assessed risk of bias (RoB). GRADE methodology was used to assess evidence certainty.

Results
We screened 4114 records and assessed 254 full texts. One RCT and one post hoc study proved eligible when comparing burosumab to conventional therapy or no treatment. The open-label RCT was at high RoB, with certainty of evidence ranging from moderate to very low. Burosumab, compared to conventional therapy, probably prevents lower limb deformity and improves physical health quality of life (QoL) (moderate certainty). Burosumab may increase height and enhance the burden of symptoms related to chronic hypophosphatemia (low certainty). Burosumab probably increases treatment-emergent adverse events (moderate certainty) and may increase dental abscesses (low certainty). One observational study assessing conventional therapy vs no treatment was at high RoB, providing very low certainty evidence regarding the impact of conventional therapy on final height.

Conclusion
Our review indicates that burosumab likely provides benefits to children by preventing lower limb deformity and improving physical health QoL while potentially increasing height. However, burosumab may also increase adverse events. Our review found limited evidence regarding the impact of conventional therapy compared to no treatment on final height. Further research is required to understand the long-term effect of medical therapy in children.
Co-Occurrence of Sotos Syndrome and Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome in 2 Patients
Authors: Mustafa Manahil , Mitscher Mary K , Johnson Nancy B , Fuqua John S 
Published: January 2025

Abstract
Sotos syndrome is an autosomal dominant condition caused by a pathogenic variant of NSD1 and characterized by a distinctive facial appearance, learning disability, and overgrowth. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by agenesis or aplasia of the uterus and upper part of the vagina in females with a normal female karyotype. The coexistence of the 2 syndromes has been reported only twice to date. We describe 2 girls with Sotos syndrome who presented with primary amenorrhea. The patient in case 1 had central precocious puberty diagnosed at age 6.5 years, which was appropriately managed for 2 years. The patient in case 2 had congenital hypothyroidism due to thyroid aplasia, treated with levothyroxine. Investigations in both girls revealed normal gonadotropin and estradiol levels. Pelvic ultrasound and magnetic resonance imaging showed absence of the uterus and the presence of normal ovaries. Based on these findings, both patients were diagnosed with müllerian agenesis/MRKH. The presence of Sotos and MRKH syndromes in these 2 patients, along with the 2 previously documented cases, might be coincidental. However, with 4 reported cases, the possibility exists for a rare link between Sotos syndrome and MRKH. Additionally, the psychosocial effect of infertility should not be underestimated.
Primary and Secondary Prevention of Obesity
Authors: Kiełczewska Aleksandra , Szcześniak Grzegorz , Kiełczewska Anna 
Published: January 2025

Introduction and purpose: Obesity is a persistent and recurring chronic condition marked by an excessive accumulation of body fat, which can deteriorate health, heighten the risk of complications, and shorten life expectancy.This review provides a comprehensive overview of the primary and secondary prevention of obesity, with a focus on interventions and strategies.
Material and methods: An extensive examination of articles published in scientific journals was carried out through online research platforms PubMed and Google Scholar. We searched articles by entering keywords in appropriate configuration: “primary prevention of obesity”, “secondary prevention of obesity”, “obesity”.
Description of the state of knowledge: According to published data, the growing problem of obesity translates into negative consequences in the form of the development of numerous complications associated with it and a shortening of the life expectancy of patients. Primary prevention of obesity includes health policy and health care that aim to prevent the development of obesity. Secondary prevention focuses on detecting and treating obesity at an early stage to prevent the development of complications.
Summary: Implementing comprehensive primary prevention strategies across the population could substantially decrease the occurrence of numerous chronic conditions associated with overweight and obesity, yet effective large-scale programs to achieve this are currently lacking.
Nurse Staffing Under Absenteeism: A Distributionally Robust Optimization Approach
Authors: Ryu Minseok , Jiang Ruiwei 
Published: January 2025

Problem definition: We study a nurse staffing problem under random nurse demand and absenteeism. Although the demand uncertainty is exogenous, the absenteeism uncertainty is decision-dependent, that is, the number of nurses who show up for work partially depends on the nurse staffing level. For quality of care, hospitals develop float pools of hospital units and train nurses to be able to work in multiple units (termed cross-training) in response to potential nurse shortages. Methodology/results: We study a distributionally robust nurse staffing (DRNS) model that considers both exogenous and decision-dependent uncertainties. We derive a separation algorithm to solve this model under a general structure of float pools. In addition, we identify several pool structures that often arise in practice and recast the corresponding DRNS model as a mixed-integer linear program, which facilitates off-the-shelf commercial solvers. Managerial implications: Through the numerical case studies, based on the data of a collaborating hospital, we found that modeling decision-dependent absenteeism improves the out-of-sample performance of staffing decisions, and such improvement is positively correlated with the value of flexibility arising from fully utilizing float pools. Funding: R. Jiang was supported in part by the National Science Foundation [Grant ECCS-1845980]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0398 .