bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diterpenoids from Scutellaria barbata D. Don Exert the Antiproliferative Effect on Colorectal Cancer Cells Via Hedgehog Signaling Pathway
Authors: Wang Wenwen , Tao Zhongyi , Tu Linglan , Huang Wenkang , Ye Yiping , Gao Lijuan , Li Xiaoyu 
Published: March 2024

Background Scutellaria barbata D. Don, also known as “Banzhilian” in China, the diterpenes of Banzhilian (Bzl-D) is a commonly used herbal medicine for treating various tumors including colorectal cancer (CRC). Objectives This study aimed to examine the function of Bzl-D in inhibiting CRC development and explore its potential targets and mechanisms involving the Hedgehog (HH) pathway. Materials and Methods To determine the major components in Bzl-D, we performed ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) analysis. The proliferation, migration, invasion, and apoptosis abilities of the CRC HT-29 cell line were examined, and the related protein expression was tested. Tumorigenesis after treatment was detected by in vivo experiments. Results Nineteen diterpenoids were detected, Bzl-D significantly inhibited the cell proliferation and metastasis and induced the apoptosis of HT-29 cells through binding to Sonic HH (SHH) and down-regulating the key proteins (SHH, patched, smoothened, and glioma-associated oncogene) of the HH pathway, thus. Of note, Bzl-D remarkably suppressed the growth of HT-29 xenografts in nude mice. Conclusion This research demonstrates that Bzl-D is a promising anti-rectal cancer drug, providing a new entry point for targeted therapy of CRC.
Conditions for modifying intraocular lenses as drug carriers for methotrexate using poly (lactic-co-glycolic acid)
Authors: Bill Clarissa , Kassumeh Stefan , Hilterhaus Christina , Tersi Natalie , Speidel Arne J , Ohlmann Andreas , Priglinger Siegfried , Priglinger Claudia , Wolf Armin , Wertheimer Christian M 
Published: March 2024

Introduction The intraocular lens (IOL) can be used as a slow-release drug carrier in cataract surgery to alleviate posterior capsular opacification (PCO). The following is a systematic development of an IOL using methotrexate and the solvent casting process with poly (lactic-co-glycolic acid) (PLGA) as a carrier polymer. Methods Different solvents for PLGA and methotrexate were tested for dissolution properties and possible damage to the IOL. The required biological concentration of methotrexate was determined in human capsular bags implanted with an IOL. To detect fibrosis, α-SMA, f-actin, and fibronectin were labelled by immunofluorescence staining. Cell proliferation and extracellular matrix contraction were observed in a lens epithelial cell line (FHL-124). Finally, the IOL was designed, and an ocular pharmacokinetic model was used to measure drug release. Results Solvent mixtures were found to allow coating of the IOL with drug and PLGA without damaging it. PCO in the capsular bag model was inhibited above 1 μM methotrexate ( p = 0.02). Proliferation in FHL-124 was significantly reduced above a concentration of 10 nM ( p = 0.04) and matrix contraction at 100 nM ( p = 0.02). The release profile showed a steady state within therapeutic range. Conclusion After determination of the required physicochemical manufacturing conditions, a drug releasing IOL was designed. A favourable release profile in an ocular pharmacokinetics model could be shown.
Efficacy of Intralesional Candida Antigen Versus Measles, Mumps, and Rubella Vaccine Versus Topical Podophyllin in Treatment of Resistant Genital Warts
Authors: Zayan Hisham , Hosny Ahmed H. , Mamdouh Meriam M. , Tawfik Yasmin M. 
Published: March 2024

Background: No single treatment is ideal for genital warts with high rate of resistance using conventional modalities as topical podophyllin; however, several intralesional immunotherapies are being tested nowadays, with variable results. In this study, we compared the safety and efficacy of treating resistant and recurrent genital warts by 2 intralesional immunotherapies [ Candida antigen and measles, mumps, and rubella (MMR) vaccine] and compared them with topical podophyllin. Patients/Methods: A total of 45 patients with resistant or recurrent genital warts were enrolled in this study. Size and number of warts were detected in each patient, patients were divided into 3 groups. Group A injected with intralesional Candida antigen. Group B with intralesional MMR vaccine. Group C were treated with topical 25% podophyllin. Patients received a session every 2 weeks for 3 treatment sessions. Results: With regard to the reduction in size and number of all warts, the best response was obtained in Candida antigen group where 46.7% showed complete clearance and 40% showed partial response followed by MMR group and the last was the podophyllin group, with no significant difference between them. Complete clearance of mother warts was noticed in 86.7% of Candida group, 53.3% in MMR group, and last 40% in podophyllin group, with a significantly better response in the Candida group ( P = .027). Conclusion: Both intralesional Candida antigen and MMR vaccine are simple, safe, and effective treatment options with comparable results and better response than topical podophyllin.
Contemporary Assessment of Adhesiolysis and Resection for Adhesive Small Bowel Obstruction in the State of New York
Authors: Symer Matthew M. , Zheng Xinyan , Pua Bradley B. , Sedrakyan Art , Milsom Jeffrey W. 
Published: March 2024

Background Adhesive small bowel obstruction (aSBO) is a common surgical problem, with some advocating for a more aggressive operative approach to avoid recurrence. Contemporary outcomes in a real-world setting were examined. Study Design A retrospective cohort study was performed using the New York Statewide Planning and Research Cooperative database to identify adults admitted with aSBO, 2016-2020. Patients were stratified by the presence of inflammatory bowel disease (IBD) and cancer history. Diagnoses usually requiring resection were excluded. Patients were categorized into four groups: non-operative, adhesiolysis, resection, and ‘other’ procedures. In-hospital mortality, major complications, and odds of undergoing resection were compared. Results 58,976 patients were included. 50,000 (84.8%) underwent non-operative management. Adhesiolysis was the most common procedure performed (n = 4,990, 8.46%), followed by resection (n = 3,078, 5.22%). In-hospital mortality in the lysis and resection groups was 2.2% and 5.9% respectively. Non-IBD patients undergoing operation on the day of admission required intestinal resection 29.9% of the time. Adjusted odds of resection were highest for those with a prior aSBO episode (OR 1.29 95%CI 1.11-1.49), delay to operation ≥3 days (OR1.78 95%CI 1.58-1.99), and non-New York City (NYC) residents being treated at NYC hospitals (OR1.57 95%CI 1.19-2.07). Conclusion Adhesiolysis is currently the most common surgery for aSBO, however nearly one-third of patients will undergo a more extensive procedure, with an increased risk of mortality. Innovative therapies are needed to reduce the risk of resection.
Laparoscopic-assisted retrieval of inferior vena cava filter: A case report and literature review
Authors: Wang Chenghao , Liu Qingquan , Xiao Dalei , Chen Xiaohua , Liu Rong , Wang Shikai 
Published: March 2024

Background The retrieval of inferior vena cava filters beyond the retrieval window poses challenges, requiring alternative techniques. Objectives To discuss the laparoscopy-assisted retrieval approach for difficult inferior vena cava filters. Research Design Case report. Subjects A 57-year-old male with a retrievable inferior vena cava filter placed 8 months prior. Measures Laparoscopy-assisted retrieval technique utilized after unsuccessful interventional attempts. Results Successful retrieval of the filter despite thickened intimal tissue involvement, with no postoperative complications. Conclusions Laparoscopy-assisted retrieval offers a direct visual approach for challenging filter removal, proving minimally invasive, safe, and effective.
Reducing the global burden of cerebral venous thrombosis: An international research agenda
Authors: Coutinho Jonathan M , van de Munckhof Anita , Aguiar de Sousa Diana , Poli Sven , Aaron Sanjith , Arauz Antonio , Conforto Adriana B , Krzywicka Katarzyna , Hiltunen Sini , Lindgren Erik , Sánchez van Kammen Mayte , Shu Liqi , Bakchoul Tamam , Belder Rosalie , van den Berg René , Boumans Elisheva , Cannegieter Suzanne , Cano-Nigenda Vanessa , Field Thalia S , Fragata Isabel , Heldner Mirjam R , Hernández-Pérez María , Klok Frederikus A , Leker Ronen R , Lucas-Neto Lia , Molad Jeremy , Nguyen Thanh N , Saaltink Dirk-Jan , Saposnik Gustavo , Sharma Pankaj , Stam Jan , Thijs Vincent , van der Vaart Michiel , Werring David J , Wong Ramos Diana , Yaghi Shadi , Yeşilot Nilüfer , Tatlisumak Turgut , Putaala Jukka , Jood Katarina , Arnold Marcel , Ferro José M 
Published: March 2024

Background: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. Aims: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. Summary of review: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. Conclusions: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.
Traditional game of spinning top gone wrong: Short communication of a pediatric facial penetrating injury
Authors: Khoo Jing Hern , Te Boon Chin , Sachlin Ida Sadja’ah 
Published: March 2024

Introduction A spinning top is a traditional game in some countries. The top is often made of wood or mud and the bottom is made of a sharp metal pin. Penetrating injuries can occur if the spinning top is incorrectly thrown. Case report We report a spinning top penetrating injury on the nose of an 8-year-old girl. Clinical examination revealed a spinning top that had penetrated her nasal bridge. Plain computed tomography (CT) of paranasal sinuses revealed a spinning top with its sharp pointed nail penetrating through the left nasal bone into the left nasal cavity. Examination under general anesthesia and rigid nasoendoscopy showed the tip of spinning top situated in between middle turbinate and nasal septum. The spinning top was then removed following the direction of entry. Discussion While air gun pellet facial injuries in pediatric patients have been reported, other playthings as culprits of facial penetrating injuries is still unheard of. Projectile objects can easily penetrate pediatric facial skeleton due to thinner facial bones. It is vital to exclude life- and sightthreatening injuries first, followed by imaging to assist decision-making and surgical planning. Computed tomography (CT) imaging is the gold standard for the radiographic evaluation of facial injuries. It assists in evaluating trauma extent, trajectory, depth, and course of foreign body. Following that, examination under anaesthesia including rigid nasal endoscopy is warranted. Conclusion We would like to highlight the importance of parental supervision and the value of pre-operative imaging. Neglecting seemingly harmless children’s toys can potentially cause fatal injuries.
Transition From Normative to Criterion-Based Grading in the Obstetrics and Gynecology Clerkship
Authors: Abraham Cynthia 
Published: March 2024

OBJECTIVES To compare grades, National Board of Medical Examiners (NBME) Shelf Exam scores, and student satisfaction with the Obstetrics and Gynecology (OB/GYN) clerkship after transitioning from normative to criterion-based grading. METHODS Between July 2021 and July 2022, the Icahn School of Medicine at Mount Sinai (ISMMS) adhered to a normative grading scheme in which ∼60% of students achieved a grade of Honors, 30% achieved a grade of High Pass and 10% achieved a grade of Pass for the OB/GYN clerkship. In July 2022, ISMMS transitioned to a criterion-based scheme. In this scheme, 6 competencies were created. Criteria were determined for each competency, delineating achieving a score of “Pass” versus “Honors” for the specific objective. Students needed to meet the criteria for Honors for 4 out of 6 of the competencies in order to ultimately receive a grade of Honors for the clerkship. The number of students achieving Honors, NBME shelf exam scores, and student clerkship satisfaction ratings between the normative and criterion-based schemes were compared. RESULTS The number of students studying in academic year (AY) 2021–2022 and AY 2022–2023 were 134 and 137, respectively. A significantly lower percentage of students received Honors in AY 2021–2022 than in AY 2022–2023 (66% vs. 96%, P < .01). Mean exam scores were significantly higher for those receiving Honors in AY 2021–2022 than in AY 2022–2023 ( P < .05); scores for AY 2021–2022 and AY 2022–2023 were 78.9, 95% CI [77.6, 80.1] and 76.7, 95% CI [75.6, 77.8], respectively. Mean exam scores for all students were not significantly different between the 2 academic cohorts (77.8 vs. 76.2, P = .06). Clerkship satisfaction rating was significantly higher in AY 2022–2023 than in AY 2021–2022 (4.1 vs. 3.7, P < .05). CONCLUSIONS These findings support a paradigm that compares learner performance to predefined measures as opposed to peer performance.
Absent leptomeningeal collateralization is associated with greatest benefit from mechanical thrombectomy in the 6-24 hour time window
Authors: Dittrich Tolga D , von Streng Tennessee , Toebak Anna M , Zietz Annaelle , Wagner Benjamin , Hänsel Martin , Sutter Raoul , Katan Mira , Peters Nils , Michels Lars , Kulcsár Zsolt , Karwacki Grzegorz M , Pileggi Marco , Cereda Carlo W , Wegener Susanne , Bonati Leo H , Psychogios Marios , De Marchis Gian Marco 
Published: March 2024

Introduction: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated. Patients and methods: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades. Results: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33–10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11–2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01–2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0–4 and a lower mortality at 3 months for the MT + BMT group. Discussion and conclusion: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis.
How Does Telehealth Expansion Change Access to Healthcare for Patients With Different Types of Substance Use Disorders?
Authors: Tilhou Alyssa Shell , Burns Marguerite , Chachlani Preeti , Chen Ying , Dague Laura 
Published: March 2024

Background: Patients with substance use disorders (SUDs) exhibit low healthcare utilization despite high medical need. Telehealth could boost utilization, but variation in uptake across SUDs is unknown. Methods: Using Wisconsin Medicaid enrollment and claims data from December 1, 2018, to December 31, 2020, we conducted a cohort study of telemedicine uptake in the all-ambulatory and the primary care setting during telehealth expansion following the COVID-19 public health emergency (PHE) onset (March 14, 2020). The sample included continuously enrolled (19 months), nonpregnant, nondisabled adults aged 19 to 64 years with opioid (OUD), alcohol (AUD), stimulant (StimUD), or cannabis (CannUD) use disorder or polysubstance use (PSU). Outcomes: total and telehealth visits in the week, and fraction of visits in the week completed by telehealth. Linear and fractional regression estimated changes in in-person and telemedicine utilization. We used regression coefficients to calculate the change in telemedicine utilization, the proportion of in-person decline offset by telemedicine uptake (“offset”), and the share of visits completed by telemedicine (“share”). Results: The cohort (n = 16 756) included individuals with OUD (34.8%), AUD (30.1%), StimUD (9.5%), CannUD (9.5%), and PSU (19.7%). Total and telemedicine utilization varied by group post-PHE. All-ambulatory: total visits dropped for all, then rose above baseline for OUD, PSU, and AUD. Telehealth expansion was associated with visit increases: OUD: 0.489, P < .001; PSU: 0.341, P < .001; StimUD: 0.160, P < .001; AUD: 0.132, P < .001; CannUD: 0.115, P < .001. StimUD exhibited the greatest telemedicine share. Primary care: total visits dropped for all, then recovered for OUD and CannUD. Telemedicine visits rose most for PSU: 0.021, P < .001; OUD: 0.019, P < .001; CannUD: 0.011, P < .001; AUD: 0.010, P < .001; StimUD: 0.009, P < .001. PSU and OUD exhibited the greatest telemedicine share, while StimUD exhibited the lowest. Telemedicine fully offset declines for OUD only. Conclusions: Telehealth expansion helped maintain utilization for OUD and PSU; StimUD and CannUD showed less responsiveness. Telehealth expansion could widen gaps in utilization by SUD type.
Evidence for antigen presentation by human neutrophils
Authors: Moffat Angus , Gwyer Findlay Emily 
Published: March 2024

Abstract
Neutrophils are the first migrating responders to sterile and infectious inflammation and act in a powerful but nonspecific fashion to kill a wide variety of pathogens. It is now apparent that they can also act in a highly discriminating fashion; this is particularly evident in their interactions with other cells of the immune system. It is clear that neutrophils are present during the adaptive immune response, interacting with T cells in complex ways that differ between tissue types and disease state. One of the ways in which this interaction is mediated is by neutrophil expression of HLA molecules and presentation of antigen to T cells. In mice, this is well established to occur with both CD4+ and CD8+ T cells. However, the evidence is less strong with human cells. Here, we assembled available evidence for human neutrophil antigen presentation. We find that the human cells are clearly able to upregulate HLA-DR and costimulatory molecules; are able to process protein antigen into fragments recognized by T cells; are able to enter lymph node T cell zones; and, in vitro, are able to present antigen to memory T cells, inducing proliferation and cytokine production. However, many questions remain, particularly concerning whether the cell-cell interactions can last for sufficient time to trigger naïve T cells. These experiments are now critical as we unravel the complex interactions between these cells and their importance for the development of human immunity.
Decryption of the survival “black box”: gene family expansion promotes the encystment in ciliated protists
Authors: Jin Didi , Li Chao , Chen Xiao , Wang Yurui , Al-Rasheid Khaled A. S. , Stover Naomi A. , Shao Chen , Zhang Tengteng 
Published: March 2024

Abstract
Background
Encystment is an important survival strategy extensively employed by microbial organisms to survive unfavorable conditions. Single-celled ciliated protists (ciliates) are popular model eukaryotes for studying encystment, whereby these cells degenerate their ciliary structures and develop cyst walls, then reverse the process under more favorable conditions. However, to date, the evolutionary basis and mechanism for encystment in ciliates is largely unknown. With the rapid development of high-throughput sequencing technologies, genome sequencing and comparative genomics of ciliates have become effective methods to provide insights into above questions.

Results
Here, we profiled the MAC genome of Pseudourostyla cristata, a model hypotrich ciliate for encystment studies. Like other hypotrich MAC genomes, the P. cristata MAC genome is extremely fragmented with a single gene on most chromosomes, and encodes introns that are generally small and lack a conserved branch point for pre-mRNA splicing. Gene family expansion analyses indicate that multiple gene families involved in the encystment are expanded during the evolution of P. cristata. Furthermore, genomic comparisons with other five representative hypotrichs indicate that gene families of phosphorelay sensor kinase, which play a role in the two-component signal transduction system that is related to encystment, show significant expansion among all six hypotrichs. Additionally, cyst wall-related chitin synthase genes have experienced structural changes that increase them from single-exon to multi-exon genes during evolution. These genomic features potentially promote the encystment in hypotrichs and enhance their ability to survive in adverse environments during evolution.

Conclusions
We systematically investigated the genomic structure of hypotrichs and key evolutionary phenomenon, gene family expansion, for encystment promotion in ciliates. In summary, our results provided insights into the evolutionary mechanism of encystment in ciliates.