bluuebunny/crossref_metadata_2025_split huggingface dataset:
The King of Chinese Medicine——Glycyrrhiza glabra (Licorice): All-round Inquiry in its Chemical Composition, Pharmacodynamics, Traditional and Medicinal Value
Authors: Dang Lingling , Jin Yajing , Yuan Ye , Shao Rui , Wang Yu 
Published: March 2024

Licorice, a perennial herb of Leguminosa, is one of the oldest and most widely used herbal medicines worldwide. Its distinct sweet flavor and rich medicinal value make it an integral component of traditional Chinese medicine (TCM) formulations, which continue to be widely employed. The main chemical constituents of licorice include triterpenoid saponins, flavonoids, and polysaccharides. Experimental and clinical studies have demonstrated that various extracts and pure compounds derived from licorice exhibit a wide range of pharmacological properties including anti-inflammatory, antioxidant, antimicrobial, antiviral, antitumor, immune-regulatory, and neuroprotective activities. The bioactive constituents of licorice offer therapeutic benefits for cardiovascular and cerebrovascular diseases, diabetes mellitus, and liver disorders. This comprehensive review discusses the primary chemical constituents of licorice and their pharmacological activities, describes in vivo and in vitro models employed for studying licorice, and its potential targets and mechanisms of action. Furthermore, we discuss the toxicological profile, side effects, dosage recommendations, and clinical applications of licorice. This review aims to establish a foundation for further research on the safe and effective utilization of licorice while facilitating an in-depth exploration of its properties and fostering the development of novel therapeutic agents.
Graphical abstract: http://links.lww.com/AHM/A102
Erdheim–Chester Disease With Eyelid and Orbital Involvement: A Review of Treatment Modalities at One Institution From 2014 to 2022
Authors: Sharma Meghan , Stevens Shanlee M. , Maeng Michelle M. , Nagornaya Natalya , Bhatia Rita G. , Wester Sara T. 
Published: March 2024

Purpose:
To review all cases of Erdheim–Chester disease (ECD) with orbital involvement treated at Bascom Palmer Eye Institute in Miami, Florida from 2014 to 2022 and compare presentations, treatment modalities, and outcomes.

Methods:
A retrospective chart review of all patients diagnosed with ECD who presented to Bascom Palmer Eye Institute from 2014 to 2022 was performed. Data collected included demographics, pretreatment history and ophthalmic examination, pathology report, treatment, subsequent examination, and relevant laboratory results. Histopathology, treatments, and outcomes were reviewed and compared between patients.

Results:
Four cases were included. Primary treatments included vemurafenib (n = 2), cobimetinib (n = 1), and prednisone (n = 1). All patients demonstrated improvement of ophthalmic symptoms. Vemurafenib was the only medical treatment that was tolerated well and resulted in significant improvement in proptosis despite some reported dry eye; all other medications were discontinued due to intolerable side effects.

Conclusions:
BRAF inhibitors such as vemurafenib have been used as novel therapy in the treatment of ECD. Vemurafenib demonstrated its utility in reducing proptosis in ECD patients at one ophthalmic institution. Vemurafenib may be a favorable treatment option for BRAF-positive ECD patients presenting with orbital disease.
Long-term safety, durability of response, cessation and switching of biologics
Authors: Mohan Arjun , Qiu Anna Y. , Lugogo Njira 
Published: March 2024

Purpose of review
Severe asthma patients suffer from decreased quality of life, and increased asthma symptoms, exacerbations, hospitalizations, and risk of death. Biologics have revolutionized treatment for severe asthma. However, with multiple biologic agents now available, clinicians must consider initial selection the long-term effectiveness of biologics. Additionally, patients have overlapping eligibilities and clinicians may consider switching between biologics for improved response. Finally, careful assessment of biologics cessation is needed for severe asthma patients who depend on these add-on therapies for asthma control.

Recent findings
Evidence for long-term durability and safety varies by biologic agent. In general, initial benefits noted from these agents (ex. exacerbation reduction) is, at minimum, sustained with long term use. Rates of adverse events and serious adverse events, including those requiring cessation of a biologics are low with long term use. Further studies are needed to understand the development of antidrug antibodies but currently their prevalence rates are low. Adverse events and insufficient efficacy are common reasons for biologic cessation or switching. Discontinuation maybe associated with waning of benefits but can be considered in certain situations. Biologic switching can be associated with improved asthma control.

Summary
Biologics are safe and effective long-term therapies for the management of asthma. Discontinuation must be carefully considered and if possible avoided. Reasons for insufficient efficacy must be evaluated and if needed, biologic switching should be considered.
Metastasis-directed therapy in oligometastatic prostate cancer
Authors: Miszczyk Marcin , Soeterik Timo , Marra Giancarlo , Matsukawa Akihiro , Shariat Shahrokh F. 
Published: March 2024

Purpose of review
To summarize the recent findings on the subject of metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (omPCa).

Recent findings
Evidence from two randomized clinical trials (RCTs) and a meta-analysis show favorable toxicity profiles, and the potential to delay androgen-deprivation therapy (ADT) for up to two years in nearly half of patients with metachronous hormone-sensitive omPCa. Another RCT showed promising results of MDT as treatment-escalation method combined with androgen receptor signaling inhibitors (ARSI) in first-line treatment for castration-resistant omPCa.
Surveys by radiation oncologists and consensus guidelines advocate for MDT across various omPCa scenarios. Multiple single-arm trials present encouraging results; however, the evidence for the benefit of MDT is still weak requiring further investigation to assess its impact on pivotal endpoints, such as survival and quality of life.

Summary
MDT is a promising approach in omPCa, and can be used to defer ADT in newly diagnosed metachronous omPCa patients, or to add to ARSI treatment at first diagnosis of castration-resistance. Ongoing prospective trials are needed to guide its optimal utilization in other settings, and patients should be informed about the evolving landscape of systemic therapies with proven survival benefits alongside MDT options.
Severe euglycemic diabetic ketoacidosis secondary to sodium-glucose co-transporter 2 inhibitor: case report and literature review
Authors: El Ess Malak S. , ElRishi Mohamed A. 
Published: March 2024

Introduction and importance:
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been implemented in treating diabetic patients for the past 10 years. Euglycemic diabetic ketoacidosis (euDKA) can be a life-threatening complication in diabetic patients. The authors report a severe euDKA with lactic acidosis in a type 2 diabetes mellitus (T2DM) patient. This report highlights the importance of the early detection and treatment of EuDKA to avoid complications.

Case presentation:
Forty-four-year-old female with T2DM had multiple visits to the emergency department with recurrent diarrhoea and vomiting. On her third visit, she presented with shortness of breath and tachypnoea, found to have severe metabolic acidosis with euglycemia. She was admitted to ICU with euDKA secondary to SGLT2i and was managed accordingly.

Clinical discussion:
The association between SGLT2i and euDKA in T2DM is controversial. SGLT2i leads to euDKA by stimulating lipolysis and ketogenesis in the setting of volume depletion, carbohydrate deficiency, and upregulation of counter-regulatory stress hormones. EuDKA can be life-threatening, especially if not diagnosed and managed properly. The treatment protocol is similar to hyperglycaemic diabetic ketoacidosis. Our case has been reported in line with the CARE criteria.34

Conclusion:
SGLT2i benefits in diabetic patients outweigh the risks. Clinicians are advised to counsel diabetic patients maintained on SGLT2 and educate them regarding holding the medication in the setting of acute illness, volume depletion, decreased oral intake, and surgery. In addition, there should be a high index of suspicion for patients presenting with metabolic acidosis in the background of SGLT2i use to provide early diagnosis and management.
Secondary neoplasm to non-hodgkin lymphoma treatment manifesting as a cancer of unknown primary: The first case in literature
Authors: Bashour George , Kheyrbek Nina , Dway Ali , Salloum Elias , Georgeos Michael , Alshehabi Zuheir 
Published: March 2024

Introduction:
Cancer of Unknown Primary (CUP) is a tumor metastasis with no detectable primary origin. A Secondary Neoplasm (SN) is defined as a tumor secondary to a prior tumor treatment and has no histological relation to that primary tumor.

Case Presentation:
We report a case of a 72-year-old female patient who presented with back pain and had a history of Non-Hodgkin lymphoma (NHL) treated with RCHOP 12 years ago. MRI showed a compression fracture in T5 and T7 vertebrae, while the PET/CT only showed hypermetabolic lytic bone lesions in these vertebrae. Pathological examination of a biopsy of these lesions suggested metastatic breast cancer, but the mammography was normal. The above clinical description indicates that our case is a Secondary Neoplasm (SN) to RCHOP treatment manifested as a cancer of unknown origin.

Discussion:
Cancer of Unknown primary is diagnosed when all screening procedures fail to find the original tumor. On the other hand, the literature showed that RCHOP treatment of Non-Hodgkin lymphoma has a 0.68% chance of causing a SN. After an extensive literature search, we found that our case, which has the combination of both CUP and SN, is the first documented case.

Conclusion:
Our case suggests that cancer patients who received chemical or radiological treatment should be screened more carefully on the long term as it is possible to developed secondary neoplasms without a primary tumor in areas difficult to diagnose with traditional screening tools.
Prolonged suppressive antibiotic therapy for inferior vena cava filter infection following emphysematous pyelonephritis and cystitis: A case report
Authors: Suzuki Yasuhiro , Kuriyama Akira 
Published: March 2024

Introduction and importance:
Infections of inferior vena cava (IVC) filters are rare. We present a case of IVC filter infection following concurrent emphysematous urinary tract infections that was finally treated with prolonged suppressive antibiotic therapy (PSAT).

Case presentation:
A 68-year-old man with pemphigoid and type 2 diabetes mellitus, who had undergone IVC filter placement, was transferred with decreased consciousness, respiratory failure, and hypotension. Computed tomography revealed gas in the left renal parenchyma and bladder wall, suggesting a diagnosis of concurrent emphysematous pyelonephritis and cystitis. While blood and urine cultures were positive for extended-spectrum beta-lactamase-producing Escherichia coli, and the patient’s general condition improved with proper antibiotic therapy, bacteremia persisted until day 10 from symptom onset. After ruling out abscesses and infectious endocarditis, the cause of persistent bacteremia was suspected to be IVC filter infection. As the IVC had been placed 12 years before, we did not remove it to avoid complications. PSAT with sulfamethoxazole-trimethoprim was continued after 6 weeks of intravenous antibiotic therapy. The patient had an uneventful course over the year following hospital discharge.

Clinical discussion:
PSAT is considered for device-related infections in patients with cardiac assist devices and artificial joints when the infection flares up or recurs even after antibiotic treatment of an adequate duration. There is no consensus regarding the optimal duration of antimicrobial therapy for IVC filter infections.

Conclusion:
Infections of implanted devices, such as IVC filters, secondary to severe infections can cause persistent bacteremia. PSAT may be an alternative option to treat IVC filter infection, when the IVC filter is considered difficult to remove.
Similar rates of reoperation for neuroma after transtibial amputations with and without targeted muscle reinnervation
Authors: Smith Thomas P. , Cognetti Daniel J. , Cook Alyssa , Lynch Thomas B. , Alderete Joseph F. , Lybeck Dustin O. , Dowd Thomas C. 
Published: March 2024

Objective:
To compare the rates of revision surgery for symptomatic neuromas in patients undergoing primary transtibial amputations with and without targeted muscle reinnervation (TMR).

Design:
Retrospective cohort study.

Setting:
Level I trauma hospital and tertiary military medical center.

Patients/Participants:
Adult patients undergoing transtibial amputations with and without TMR.

Intervention:
Transtibial amputation with targeted muscle reinnervation.

Main Outcome Measurements:
Reoperation for symptomatic neuroma.

Results:
During the study period, there were 112 primary transtibial amputations performed, 29 with TMR and 83 without TMR. Over the same period, there were 51 revision transtibial amputations performed, including 23 (21%) in the patients undergoing primary transtibial amputation at the study institution. The most common indications for revision surgery were wound breakdown/dehiscence (42%, n = 25), followed by symptomatic neuroma 18% (n = 9/51) and infection/osteomyelitis (17%, n = 10) as the most common indications. However, of the patients undergoing primary amputation at the study's institution, there was no difference in reoperation rates for neuroma when comparing the TMR group (3.6%, n = 1/28) and no TMR group (4.0%, n = 3/75) (P = 0.97).

Conclusions:
Symptomatic neuroma is one of the most common reasons for revision amputation; however, this study was unable to demonstrate a difference in revision surgery rates for neuroma for patients undergoing primary transtibial amputation with or without targeted muscle reinnervation.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
AI-Based Measurement of Lumbar Spinal Stenosis on MRI
Authors: Bogdanovic Sanja , Staib Matthias , Schleiniger Marco , Steiner Livio , Schwarz Leonardo , Germann Christoph , Sutter Reto , Fritz Benjamin 
Published: March 2024

Objectives
The aim of this study was to clinically validate a fully automated AI model for magnetic resonance imaging (MRI)–based quantifications of lumbar spinal canal stenosis.

Materials and Methods
This retrospective study included lumbar spine MRI of 100 consecutive clinical patients (56 ± 17 years; 43 females, 57 males) performed on clinical 1.5 (51 examinations) and 3 T MRI scanners (49 examinations) with heterogeneous clinical imaging protocols. The AI model performed segmentations of the thecal sac on axial T2-weighted sequences. Based on these segmentations, the anteroposterior (AP) and mediolateral (ML) distance, and the area of the thecal sac were measured in a fully automated manner. For comparison, 2 fellowship-trained musculoskeletal radiologists performed the same segmentations and measurements independently. Statistics included 1-sample t tests, the intraclass correlation coefficient (ICC), Bland-Altman plots, and Dice coefficients. A P value of <0.05 was considered statistically significant.

Results
The average measurements of the AI model, reader 1, and reader 2 were 194 ± 72 mm2, 181 ± 71 mm2, and 179 ± 70 mm2 for thecal sac area, 13 ± 3.3 mm, 12.6 ± 3.3 mm, and 12.6 ± 3.2 mm for AP distance, and 19.5 ± 3.9 mm, 20 ± 4.3 mm, and 19.4 ± 4 mm for ML distance, respectively. Significant differences existed for all pairwise comparisons, besides reader 1 versus AI model for the ML distance and reader 1 versus reader 2 for the AP distance (P = 0.1 and P = 0.21, respectively). The pairwise mean absolute errors among reader 1, reader 2, and the AI model ranged from 0.59 mm and 0.75 mm for the AP distance, from 1.16 mm to 1.37 mm for the ML distance, and from 7.9 mm2 to 15.54 mm2 for the thecal sac area. Pairwise ICCs among reader 1, reader 2, and the AI model ranged from 0.91 and 0.94 for the AP distance and from 0.86 to 0.9 for the ML distance without significant differences. For the thecal sac area, the pairwise ICC between both readers and the AI model of 0.97 each was slightly, but significantly lower than the ICC between reader 1 and reader 2 of 0.99. Similarly, the Dice coefficient and Hausdorff distance between both readers and the AI model were significantly lower than the values between reader 1 and reader 2, overall ranging from 0.93 to 0.95 for the Dice coefficients and 1.1 to 1.44 for the Hausdorff distances.

Conclusions
The investigated AI model is reliable for assessing the AP and the ML thecal sac diameters with human level accuracies. The small differences for measurement and segmentation of the thecal sac area between the AI model and the radiologists are likely within a clinically acceptable range.
Typical Bone Scintigraphy Presentation of Erdheim-Chester Disease in a Patient Diagnosed With IgG4-Related Disease
Authors: François Chloé , Rousselin Clémentine , Quemeneur Thomas , Demailly Franck , Collet Guillaume , Fagart Alexandre 
Published: March 2024

Abstract
A 50-year-old woman presented a dry syndrome, joint pain, inflammatory syndrome, polyclonal hypergammaglobulinemia, and tubulointerstitial nephritis. Imaging studies (including FDG PET/CT) revealed infrarenal retroperitoneal fibrosis with periaortitis and hypermetabolic osteosclerotic lesions. Bone scintigraphy demonstrated intense uptake in the femoral, tibial, and radial regions, suggestive of non-Langerhans histiocytosis, specifically Erdheim-Chester disease. A bone biopsy confirmed the presence of IgG4-positive plasma cells but no histiocytes. The patient received corticosteroid therapy followed by rituximab, resulting in a complete response. This case suggests an atypical manifestation of bone lesions in IgG4-related disease, emphasizing the diagnostic challenge between IgG4-related disease and Erdheim-Chester disease.
Increased Prostate-Specific Membrane Antigen Uptake in a Gallbladder Stone
Authors: Li Hui , Song Le , Zhao Meixin , Zhang Weifang 
Published: March 2024

Abstract
An Al 18F–prostate-specific membrane antigen (PSMA) Q PET/CT scan was performed in a 67-year-old man to identify any potential recurrent prostate cancer lesions, which revealed no recurrent or metastatic lesions. However, a large gallbladder stone with increased PSMA uptake was incidentally detected, which could be a potential pitfall in the interpretation of PSMA PET imaging.
Device for Axon - Cancer cell Interaction Testing in 2D & 3D: DACIT
Authors: Velazquez-Quesada Ines , Alizadeh Vahid , Allison Kara , Belova Elizaveta , Kallogjerovic Svetllana , Hesketh Natasha , Zhang Xiaotian , Thomas Gareth , Tuzel Erkan , Gligorijevic Bojana 
Published: March 2024

SummaryThere is increasing interest in studying the role of peripheral innervation in tumor growth and metastasis. However,in vitrostudies of interactions between cancer cells and axonal projections are technically challenging. To address this, we have developed a microfluidic Device for Axon-Cancer cell Interaction Testing in 2D and 3D (DACIT). We show that DACIT successfully separates neuronal soma from the axons and cancer cells into two compartments, which can be exposed to similar, or different growth conditions, depending on the experimental needs. We compare neoaxonogenesis using either the PC-12 cell line or primary embryonic or adult sensory neurons, demonstrating superior neurite growth in primary cells. Additionally, we show that DACIT can accommodate assessing growth and 3D invasion of tumor spheroids, due to its unique height profile. Hence, DACIT can be used to analyze cancer cell interactions with axons in most typical cell biology assays such as proliferation, invasion, and calcium activity which we demonstrate on examples of imaging transients in GCaMP6-labeled neurons, invadopodia assay, and 3D cancer spheroid invasion.
Physical-Chemical Features Selection Reveals That Differences in Dipeptide Compositions Correlate Most with Protein-Protein Interactions
Authors: Teimouri Hamid , Medvedeva Angela , Kolomeisky Anatoly B. 
Published: March 2024

AbstractThe ability to accurately predict protein-protein interactions is critically important for our understanding of major cellular processes. However, current experimental and computational approaches for identifying them are technically very challenging and still have limited success. We propose a new computational method for predicting protein-protein interactions using only primary sequence information. It utilizes a concept of physical-chemical similarity to determine which interactions will most probably occur. In our approach, the physical-chemical features of protein are extracted using bioinformatics tools for different organisms, and then they are utilized in a machine-learning method to identify successful protein-protein interactions via correlation analysis. It is found that the most important property that correlates most with the protein-protein interactions for all studied organisms is dipeptide amino acid compositions. The analysis is specifically applied to the bacterial two-component system that includes histidine kinase and transcriptional response regulators. Our theoretical approach provides a simple and robust method for quantifying the important details of complex mechanisms of biological processes.
PROTAC-mediated dual degradation of BCL-xL and BCL-2 is a highly effective therapeutic strategy in small-cell lung cancer
Authors: Khan Sajid , Cao Lin , Wiegand Janet , Zhang Peiyi , Zajac-Kaye Maria , Kaye Frederic J. , Zheng Guangrong , Zhou Daohong 
Published: March 2024

ABSTRACTBCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax. We have developed a strategy to selectively target BCL-xL in tumors, while sparing platelets, by utilizing proteolysis-targeting chimeras (PROTACs) that hijack the cellular ubiquitin proteasome system for target ubiquitination and subsequent degradation. In our previous study, the first-in-class BCL-xL PROTAC, called DT2216, was shown to have synergistic antitumor activities when combined with venetoclax (formerly ABT199, BCL-2-selective inhibitor) in a BCL-xL/2 co-dependent SCLC cell line, NCI-H146 (hereafter referred to as H146),in vitroand in a xenograft model. Guided by these findings, we evaluated our newly developed BCL-xL/2 dual degrader, called 753b, in three BCL-xL/2 co-dependent SCLC cell lines and the H146 xenograft models. 753b was found to degrade both BCL-xL and BCL-2 in these cell lines. Importantly, it was considerably more potent than DT2216, navitoclax, or DT2216+venetoclax to reduce the viability of BCL-xL/2 co-dependent SCLC cell lines in cell culture.In vivo, 5 mg/kg weekly dosing of 753b leads to significant tumor growth delay similar to the DT2216+venetoclax combination in H146 xenografts by degrading both BCL-xL and BCL-2. Additionally, 753b administration at 5 mg/kg every four days induced tumor regressions. 753b at this dosage was well tolerated in mice without induction of severe thrombocytopenia as seen with navitoclax nor induced significant changes in mouse body weights. These results suggest that the BCL-xL/2 dual degrader could be an effective and safe therapeutic for a subset of SCLC patients warranting clinical trials in future.