bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Functional Mechanism of Action of Sanxiankaixin Powder in Preventing and Treating Reproductive Aging Based on Network Pharmacology and Molecular Docking
Authors: Liu Zhiming , Li Zhong , Sun Yuan , Zhao Feng , Chen Shaofeng , Zhao Yu , Zhang Zhe , Liao Zhihui , Geng Qiang 
Published: December 2024

Background:
To explore the functional mechanism of Sanxiankaixin powder (SXKXP) in preventing and treating reproductive aging (RA) through network pharmacology and molecular docking technology.

Methods:
The traditional Chinese medicine systems pharmacology database and analysis platform was utilized to identify the major active components of SXKXP. The SwissTargetPrediction algorithm was used to identify potential SXKXP targets for RA prevention and treatment. GeneCards and OMIM were used to identify RA disease targets, whereas Venny 2.1.0 was utilized to find common targets. Protein-protein interaction analysis was conducted with STRING, and network diagrams were created with Cytoscape. We performed a gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the DAVID database. The compound-drug–component-core target-KEGG pathway networks were created with Cytoscape software. Finally, we used PubChem, UniProt, PDB, PyMoL, and AutoDock software for molecular docking.

Results:
It was found that 93 effective components in SXKXP directly acted on 56 core disease targets to prevent and treat RA through multiple pathways, among which kaempferol, luteolin, 8-Prenylkaempferol, quercetin, and Schisandrol B were the core components, and AKT1, estrogen receptor 1 (ESR1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tumor necrosis factor (TNF), and interleukin 6 (IL-6) were important targets. The results of the GO enrichment analysis showed that apoptosis, cell proliferation, plasma membrane, and ATP binding may be closely related to RA. The KEGG pathway enrichment analysis results suggested that the AGE-RAGE signaling pathway in diabetic complications and the PI3K-Akt signaling pathway play important roles. Molecular docking results suggested that the core components were well bound to important targets.

Conclusion:
SXKXP interferes with biological processes such as oxidation and inflammatory reactions through multiple targets and pathways to prevent and treat RA. This study provides the research direction and theoretical basis for the experimental research of SXKXP on RA prevention and treatment.
Phase 2 study of the safety and efficacy of QTORIN rapamycin in the treatment of microcystic lymphatic malformations
Authors: Treat James , Martini Jeffrey , Connor Jason T. , Small Alison , Funk Tracy , Waner Milton , Teng Joyce 
Published: December 2024

Objectives:
The objective of this Phase 2 study was to determine the safety and efficacy of QTORIN rapamycin 3.9% anhydrous gel for the treatment of cutaneous microcystic lymphatic malformations (LM).

Design:
The study was a multicenter, baseline-controlled Phase 2 clinical trial.

Setting:
The study was performed at 5 clinical sites in the United States.

Participants:
Participants were ≥6 years old with a clinical diagnosis of cutaneous microcystic LM.

Intervention:
Participants self-administered topical QTORIN rapamycin once daily for 12 weeks.

Main Outcome Measurements:
Outcomes were measured via standardized clinician- and patient-reported outcomes, including clinician global impression of change, clinician global impression of severity (CGI-S), patient global impression of severity, patient global impression of change (PGI-C), as well as lesion leaking or bleeding, thickness/height/size of lesion, LM symptom severity scale, dermatology life quality index, and overall patient satisfaction.

Results:
Safety, clinical examinations, laboratory evaluations, and quantification of sirolimus blood levels, suggested that QTORIN rapamycin was generally safe and well-tolerated. Efficacy indicated statistically significant improvements in endpoints with treatment. Clinician and patient reports were supported by visual photographs showing significant improvement in lesions over the course of treatment.

Conclusions:
This Phase 2 study provides compelling evidence of the safety and efficacy of QTORIN rapamycin, a novel 3.9% topical sirolimus formulation, for the treatment of microcystic LM and supports further development including a larger trial in this patient population.
The evolution of a quality improvement curriculum in a family nurse practitioner residency program
Authors: Yamada Kiera , Price Paula Susanne , Gorgone Bronwyn , Robertson Bethany 
Published: December 2024

ABSTRACT
There is a wide variation in the curricular emphasis and implementation nationally across programs for teaching quality improvement (QI) in family nurse practitioner (FNP) programs. This variation among curriculum plans often leaves NP graduates unsure as to how to identify and effect change within their organizations. This manuscript describes the development of an initial QI curriculum and subsequent enhancements over a 3-year time frame and outlines the curriculum development process, implementation, and program outcomes within an FNP residency program. This report also focuses on the importance of reinforcing the role of QI within the personal identity of the FNP, ensuring quality care to patients.
The role of eosinophil counts and megakaryocyte nuclei for distinction of acute and chronic immune thrombocytopenic purpura
Authors: Cilesiz Kubra , Kocak Ulker , Kaya Zuhre , Yenicesu Idil 
Published: December 2024

Objective
Immune thrombocytopenic purpura (ITP), the most common cause of thrombocytopenia, is clinically classified as acute and chronic. This study aimed to distinguish between acute/chronic ITP parameters examined at diagnosis via complete blood count (CBC), peripheral blood (PB) and bone marrow aspirate (BMA) smears. It would also contribute to early treatment options, cost-effective policies, and the life quality of patients.

Methods
This study consisted of 304 ITP patients aged under 18 years diagnosed and followed up between 1982–2018. Differences between acute and chronic groups were compared by eosinophilia, megakaryocytes (MKs), and megakaryocyte nuclei. Diagnostic scales were created using simple parameters both to guide the distinction between acute and chronic ITP as well as for the prediction of the chronic progression of the patients at diagnosis.

Results
Of the patients in this study, 71% had acute and 29% had chronic ITP. In CBC and PB smears, eosinophil and lymphocyte counts were higher in acute whereas neutrophil counts were higher in chronic ITP patients. Eosinophil counts in the BMA were also significantly higher in acute ITP patients. There was no significant difference in MK counts. However, the mean number of MK nuclei was higher in acute ITP patients.

Conclusion
Comparison analyses between acute/chronic ITP with the methods developed for the first time are low-cost and promising. Using only eosinophil percentages in the CBC and PB smear, we could identify acute cases by 100%. Further studies including the integration of our study and clinical risk scoring models would contribute to the diagnosis and treatment process of ITP.
A case report on metastatic prostate cancer with normal PSA level diagnosed by immunohistochemistry and its management
Authors: Bhandari Kritick , Chothe Saili , Pandey Saujanya Jung , Karki Devendra , Shah Sanjit Kumar , Tandukar Shree Krishna , Jha Rahul 
Published: December 2024

Introduction and importance:
Metastatic prostate cancer (mPCa) is an advanced form of cancer that spreads beyond the prostate to distant organs such as bones and lymph nodes. While prostate-specific antigen (PSA) testing is commonly used for diagnosis, rare cases with normal PSA levels complicate detection. This case highlights the crucial role of immunohistochemistry (IHC) in diagnosing mPCa with normal PSA and its management in resource-limited settings.

Case presentation:
A 63-year-old male presented with 2 months of persistent back pain without neurological deficits. Initial diagnostics, including PSA levels, CT, MRI, and TRUS guided prostate biopsy, revealed no prostate abnormalities. However, an MRI and Bone scan showed a suspicious vertebral lesion, and a subsequent biopsy confirmed malignancy. IHC demonstrated overexpression of alpha-methyl acyl-CoA racemase (AMACR), leading to the diagnosis of mPCa. The patient underwent bilateral subcapsular orchiectomy and received external beam radiotherapy (EBRT) to manage symptoms and control disease progression.

Clinical discussion:
This case highlights the diagnostic challenges of mPCa in patients with normal PSA levels. Standard diagnostics, including imaging and biopsy, may fail to detect prostate cancer, making IHC, specifically AMACR, an essential tool for diagnosis. Early surgical intervention followed by EBRT offered significant symptomatic relief and disease control.

Conclusion:
This case demonstrates the importance of IHC in diagnosing atypical presentations of mPCa with normal PSA. A multidisciplinary approach combining surgery and radiotherapy can improve outcomes and quality of life, even in resource-limited settings
Extensive surveillance of mosquitoes and molecular investigation of arboviruses in Central Iran
Authors: Abedi-Astaneh Fatemeh , Rad Hedaiatollah R. , Izanlou Hassan , Hosseinalipour Seied A. , Hamta Amir , Eshaghieh Mohammad , Ebrahimi Mahdi , Ansari-Cheshmeh Mohammad A. , Pouriayevali Mohammad H. , Salehi-Vaziri Mostafa , Jalali Tahmineh , Talbalaghi Asghar , Abbasi Ebrahim 
Published: December 2024

Background:
Arboviruses are one of the greatest threats to animal and public health. Culicidae family is one of the most important vectors for the transmission of arboviruses in the world. According to the geographical, demographic, and climatic features of Qom city in Iran, it can be a suitable region for vectors and therefore transmission of arboviruses.

Methods:
In this study, which was conducted between 2019 and 2020 in different parts of Qom city, 83 414 mosquitoes were collected, and after evaluating the species of mosquitoes based on morphological and molecular detection, the presence of alphaviruses, flaviviruses, and phleboviruses were evaluated using genus-specific Reverse transcription polymerase chain reaction (RT-PCR) assays.

Results:
In this study, Culex tarsalis, Culex theileri, and Culex quinquefasciatus were detected, including the first recorded presence of Culex tarsalis in Iran. No infections with alphavirus, flavivirus, or phlebovirus were identified in the collected mosquitoes.

Conclusion:
Climatic and weather changes are the basis for the growth and spread of vectors and, consequently, the spread of arboviral diseases, and this issue seems to be very important to the necessity of increasing and continuing entomological and virological studies.
FDG PET/CT and MRI of IgG4-Related Disease Presenting as a Hepatic Solitary Solid Mass
Authors: Ma Wanjun , Luo Yongjun , Wang Furong , Liu Jiangyan 
Published: December 2024

Abstract
A hepatic solitary solid mass mimicking malignancy was discovered through MRI and FDG PET/CT in a 76-year-old woman with abdominal pain and no abnormal tumor markers in the blood. She underwent surgery to remove the lesion. Histopathology with biopsy was highly suspicious for IgG4-related disease, although immunohistochemical staining demonstrated non–IgG4-positive plasma cells. Finally, intrahepatic IgG4-related disease was supported by elevated serum IgG4 of 141 mg/dL. IgG4-related disease could manifest as hepatic solitary solid mass without any other organ involvement, and the immunohistochemical staining of IgG4 may be negative.
Retrospective cohort study of the economic value of providing microprocessor knees to the population of Medicare fee-for-service K2 beneficiaries with a knee disarticulation/above knee amputation
Authors: Dobson Al , Beins Michael , DaVanzo Joan , Kim Seung , McMahon Patrick , Haught Randall , Hasselbrink Roger , Gonzalez Sky , Kannenberg Andreas , Seidinger Susanne 
Published: December 2024

Background:
Microprocessor knees (MPKs) improve the functional mobility, quality of life, and safety of individuals with a knee disarticulation or above knee amputation and are cost-effective when adjusting for quality-of-life years gained. However, few studies have been conducted on the K2 population, and to this point, the Centers for Medicare and Medicaid Services has not covered MPKs for the K2 population.

Objectives:
The aim of this study was to determine the extent to which MPK provision to the K2 population is cost effective at the person and population levels. A secondary objective was to determine the effectiveness of MPKs at reducing injurious falls within the K2 population.

Study design:
A retrospective cohort study using Medicare fee-for-service claims data from the Centers for Medicare and Medicaid Services.

Methods:
Propensity score weighting using inverse probability treatment weights was used to balance beneficiary characteristics and a generalized linear regression with log-link function and Gamma distribution was run to determine per-member-per-month cost and prosthetic device cost. A 10-year Congressional Budget Office-style score was conducted. A logistic regression was run for the fallers analysis.

Results:
Microprocessor knee provision to K2 beneficiaries reduced injured fallers by 18.5% and resulted in medical savings of $1,351 per-member-per-month, amortizing the $25,075 difference between the MPK and nonmicroprocessor knee in 19 months. Providing MPKs to K2 users resulted in cumulative Medicare savings of $410.3 million over 10 years.

Conclusion:
The MPK prosthetic device could provide meaningful safety benefits to the K2 population and result in fiscal savings to Medicare at both the person and population levels.
Liver Allograft Cirrhosis, Retransplant, and Mortality Secondary to Recurrent Disease After Transplant for MASH: A Systematic Review and Meta-analysis
Authors: Jatana Sukhdeep , Krys Daniel , Verhoeff Kevin , Kung Janice Y. , Jogiat Uzair , Montano-Loza Aldo J. , Shapiro A.M. James , Dajani Khaled , Anderson Blaire , Bigam David L. 
Published: December 2024

Background.
Recurrent disease after liver transplant is well recognized for many diseases. Metabolic dysfunction–associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are leading indications for liver transplant, and there is scarce knowledge about recurrence-related end outcomes such as retransplant and mortality. This project aims to assess the proportion of patients transplanted for MASH who develop recurrent disease and adverse clinical outcomes.

Methods.
A systematic review and pooled proportions meta-analysis was performed by searching the following databases: MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library. Inclusion criteria were studies discussing adult patients with liver transplants secondary to MASH or presumed MASH with recurrent disease-related outcomes. Outcomes were assessed in time frames from <6 mo to ≥5 y.

Results.
Of 5859 records, 40 were included (16 157 patients). Recurrent MASLD and MASH (28 studies each) occurred in frequencies of 35%–49% and 11%–24%, respectively. Fibrosis occurred in 4%–25% (13 studies). Recurrent disease-related cirrhosis (13 studies), graft failure (8 studies), and retransplant (9 studies) occurred in 0%–2%, 3%–9%, and 0%–1%, respectively. Recurrent disease-related hepatocellular carcinoma (1 study) and mortality (17 studies) both had a prevalence of 0%. Studies were of moderate or high quality using the Methodological Index for Non-Randomized Studies tool.

Conclusions.
Recurrent MASLD and MASH after liver transplant occur frequently, but adverse clinical outcomes due to disease recurrence are infrequent, maybe due to insufficient data on long-term follow-up. Long-term outcomes after transplantation for MASLD appear favorable; however, identifying those more likely to have progressive recurrent disease leading to adverse clinical outcomes may allow for pre- and posttransplant interventions to improve outcomes further.
Diminishing Returns: An Analysis of Surgeon Compensation in the Setting of Ever-Increasing Student Debt
Authors: Sickels Angela D , McElroy Katherine , Robinson Joshua , Chen Herbert , Rose J Bart 
Published: December 2024

Background:
The knowledge required to manage surgical patients has expanded considerably over the past 40 years. Simultaneously, the cost of medical education has increased substantially. Surgical trainees are at particular disadvantage due to the time demands of training. We aim to determine whether surgeon compensation over time has adequately accounted for increasing student debt burden.

Study Design:
We conducted a retrospective review of data on surgeon salaries and medical education debt from the Medical Group Management Association and Association of American Medical Colleges (2014-2019). Inflation adjustment was performed using the consumer price index calculator from the United States Bureau of Labor and Statistics. Outcomes of interest included trends in debt, salaries, and the debt:income ratio.

Results:
The median salary for a general surgeon in 1984 was $111,287 and median medical school debt was $22,000, corresponding to a salary of $274,900 and $54,344 in 2019 dollars, respectively, representing a 147% increase. The reported median salary for a general surgeon in 2019 was $350,000 (214.5% increase) and medical school debt was $200,000 (809% increase). The debt:income ratio increased from 0.2 in 1984 to 0.57 in 2012 and has remained stable since that time. Direct comparison of loan burden and salary reveals that while medical school debt has increased by 268% in the past 40 years, surgeon salaries have increased as well, but not nearly to the same degree (27.3%).

Conclusions:
The rate of debt accumulation has outpaced the rate of salary growth for general surgeons to a significant degree.
Single-nucleus RNA sequencing of human periventricular white matter in vascular dementia
Authors: Díaz-Pérez Sebastián , DeLong Jonathan H. , Rivier Cyprien A. , Lee Chia-Yi , Askenase Michael H. , Zhu Biqing , Zhang Le , Brennand Kristen J. , Martins Andrew J. , Sansing Lauren H. 
Published: December 2024

AbstractVascular dementia (VaD) refers to a variety of dementias driven by cerebrovascular disease and is the second leading cause of dementia globally. VaD may be caused by ischemic strokes, intracerebral hemorrhage, and/or cerebral small vessel disease, commonly identified as white matter hyperintensities on MRI. The mechanisms underlying these white matter lesions in the periventricular brain are poorly understood. In this study we perform an extensive transcriptomic analysis on human postmortem periventricular white matter lesions in patients with VaD with the goal of identifying molecular pathways in the disease. We find increased cellular stress responses in astrocytes, oligodendrocytes, and oligodendrocyte precursor cells as well as transcriptional and translational repression in microglia in our dataset. We show that several genes identified by GWAS as being associated with white matter disease are differentially expressed in cells in VaD. Finally, we compare our dataset to an independent snRNAseq dataset of PVWM in VaD and a scRNAseq dataset on human iPSC-derived microglia exposed to oxygen glucose deprivation (OGD). We identify the increase of the heat shock protein response as a conserved feature of VaD across celltypes and show that this increase is not linked to OGD exposure. Overall, our study is the first to show that increased heat shock protein responses are a common feature of lesioned PVWM in VaD and may represent a potential therapeutic target.
Element partitioning, element localisation and transcriptome responses of date palms exposed to NaCl
Authors: Pongrac Paula , Fischer Sina , Wright Gladys , Thompson Jacqueline A. , Kelemen Mitja , Neugebauer Konrad , Brown Lawrie K. , Vogel-Mikuš Katarina , Šala Martin , El-Serehy Hamed A. , White Philip J. 
Published: December 2024

ABSTRACTDate palm (Phoenix dactyliferaL.) is an economically important fruit crop in many (semi)arid regions. Large intra-species variation in susceptibility to NaCl has been reported. Controlled experiments were conducted to evaluate sodium (Na) and chlorine (Cl) partitioning in two-year old plants of six date palm varieties and to determine tissue location of Na and Cl and transcriptome responses to NaCl of two varieties. The largest Na concentrations were found in secondary roots, especially under NaCl treatment. By contrast, only small differences in within-plant partitioning of Cl were observed with less differences between varieties than for Na. Variety Sultana had the largest Na translocation factor. The variety Khalas exhibited better restriction of Na mobility, which may be a consequence of Na hotspots in roots, presumably immobilising Na in roots, which were absent in Sultana. In the root, shoot base and lower part of leaves, Cl accumulated in fibre bands and sclerenchyma sheaths of vascular bundles. RNAseq analysis revealed that Sultana and Khalas respond very differently to NaCl: Khalas modified expression of NaCl-specific genes in both roots and leaves, while Sultana responded manly in leaves. Gene ontology analysis showed that the expression changes for genes linked with photosynthesis and carbohydrate metabolism predominated as a response to NaCl. In Khalas, differentially expressed genes encoding for metal transporters and those reported to be involved in heat, salt and osmotic stress response were found. Large variability in Na and Cl accumulation in different date palm varieties may have practical agronomical consequences.
ASSOCIATION BETWEEN CIRCADIAN RHYTHMS, SLEEP, AND DEPRESSION: A BIDIRECTIONAL MENDELIAN RANDOMISATION STUDY IN THE UK BIOBANK
Authors: Paz Valentina , Williams Dylan M , Richards Marcus , Tassino Bettina , Silva Ana , Garfield Victoria 
Published: December 2024

AbstractIncreasing evidence links circadian and sleep disruptions with depression, though whether they are causally related remains unclear. This study used Mendelian randomization (MR) with exposures instrumented using genome-wide genetic variants and data from the UK Biobank (n=408 480; mean age=56.9 years) to explore causal associations between circadian and sleep traits, and depression. We conducted bidirectional MR analyses between morningness, sleep duration, insomnia symptoms, and depression, and secondary unidirectional analyses with circadian and sleep traits as exposures and mixed anxiety-depressive symptoms and anxiety disorders as outcomes. Using inverse-variance weighting and sensitivity analyses for horizontal pleiotropy (MR-Egger and Weighted Median Estimator), we found suggestive associations between morningness and lower odds of depression (diagnosis and treatment: OR=0.89, 95%CI=0.80, 0.98), and depression and shorter sleep duration (β=-4.67 minutes, 95%CI=-7.44; -1.89). Depression showed an effect on insomnia (any symptoms: OR=1.22, 95%CI=1.11; 1.34; frequent symptoms: OR=1.30, 95%CI=1.19; 1.42), while frequent insomnia was associated with increased odds of depression (diagnosis: OR=1.14, 95%CI=1.10; 1.19; diagnosis and treatment: OR=1.10, 95%CI=1.06; 1.14). Insomnia also had an effect on mixed anxiety-depressive symptoms (any symptoms: OR=1.19, 95%CI=1.08, 1.32; frequent symptoms: OR=1.20, 95%CI=1.17, 1.23), but no associations were found between the exposures and anxiety disorders. These findings shed light on the causal links between the circadian system and depression.