bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethynylestradiol feminizes gene expression partly in testis developing as ovotestis and disrupts asymmetric Müllerian duct development by eliminating asymmetric gene expression in Japanese quail embryos
Authors: Abe Natsuko , Sakiyama Akari , Suzuki Maho , Win-Shwe Tin-Tin , Suzuki Takehiro , Kawashima Takaharu , Tsukahara Shinji
Published: March 2024

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc, P45017α, lyase, and 3β-HSD) and estrogen receptor-β, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development.
Digital assets and private law: is there a need for a uniform law?
Authors: Bazinas Spyridon V
Published: March 2024

The various legislative initiatives around the world on the private law aspects of digital assets are a clear indication of both the importance and the urgency of preparing rules of law to adjust private law in general and secured transactions law in particular to address emerging technologies. All these initiatives raise the question whether principles would be sufficient or whether a uniform law would need to be prepared. The purpose of this article is not to attempt to answer this question but rather to advance the discussion setting out some arguments in favour and against, and to suggest a mechanism, a procedure through which States and industry could reach consensus on the most appropriate answers.
Non-Operative Treatment of Humeral Shaft Fractures with Immediate Functional Bracing versus Coaptation Splinting and Delayed Functional Bracing: A Retrospective Study
Authors: Muhammad Maaz , Foster Jeffrey A. , Griffin Jarod T. , Kinchelow Daria L. , Sierra-Arce Carlos R. , Southall Wyatt G. S. , Albitar Ferras , Moghadamian Eric S. , Wright Raymond D. , Matuszewski Paul E. , Zuelzer David A. , Primm Daniel D. , Hawk Gregory S. , Aneja Arun
Published: March 2024

OBJECTIVES:

To compare radiographic and clinical outcomes in non-operative management of humeral shaft fractures treated initially with coaptation splinting (CS) followed by delayed functional bracing (FB) versus treatment with immediate FB.

METHODS:

Design: Retrospective cohort study

Setting:

Academic Level 1 Trauma Center

Patient Selection Criteria:

Patients with closed humeral shaft fractures managed non-operatively with initial CS followed by delayed FB or with immediate FB from 2016 to 2022. Patients younger than 18 years and/or with less than 3 months follow-up were excluded.

Outcome Measures and Comparisons: The primary outcome was coronal and sagittal radiographic alignment assessed at final follow-up. Secondary outcomes included rate of failure of non-operative management (defined as surgical conversion and/or fracture nonunion), fracture union, and skin complications secondary to splint/brace wear.

RESULTS:

Ninety-seven patients were managed non-operatively with delayed FB (n=58) or immediate FB (n=39). Overall, the mean age was 49.9 years (range 18-94), and 64 (66%) patients were female. The immediate FB group had less smokers (p=0.003) and lower incidence of radial nerve palsy (p=0.025), with more proximal third humeral shaft fractures (p=0.001). There were no other significant differences in demographic or clinical characteristics (p>0.05). There were no significant differences in coronal (p=0.144) or sagittal (p=0.763) radiographic alignment between groups. In total, 33 (34.0%) humeral shaft fractures failed non-operative management, with 11 (28.2%) in the immediate FB group, and 22 (37.9%) in the delayed FB group (p=0.322). There were no significant differences in fracture union (p=0.074) or skin complications (p=0.259) between groups.

CONCLUSIONS:

This study demonstrated that non-operative treatment of humeral shaft fractures with immediate functional bracing did not result in significantly different radiographic or clinical outcomes compared to treatment with coaptation splinting followed by delayed functional bracing. Future prospective studies assessing patient reported outcomes (PROs) will further guide clinical decision making.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Measures and Impact of Caseload Surge During the COVID-19 Pandemic: A Systematic Review*
Authors: Neupane Maniraj , De Jonge Nathaniel , Angelo Sahil , Sarzynski Sadia , Sun Junfeng , Rochwerg Bram , Hick John , Mitchell Steven H. , Warner Sarah , Mancera Alex , Cooper Diane , Kadri Sameer S.
Published: March 2024

OBJECTIVES:

COVID-19 pandemic surges strained hospitals globally. We performed a systematic review to examine measures of pandemic caseload surge and its impact on mortality of hospitalized patients.

DATA SOURCES:

PubMed, Embase, and Web of Science.

STUDY SELECTION:

English-language studies published between December 1, 2019, and November 22, 2023, which reported the association between pandemic “surge”-related measures and mortality in hospitalized patients.

DATA EXTRACTION:

Three authors independently screened studies, extracted data, and assessed individual study risk of bias. We assessed measures of surge qualitatively across included studies. Given multidomain heterogeneity, we semiquantitatively aggregated surge–mortality associations.

DATA SYNTHESIS:

Of 17,831 citations, we included 39 studies, 17 of which specifically described surge effects in ICU settings. The majority of studies were from high-income countries (n= 35 studies) and included patients with COVID-19 (n= 31). There were 37 different surge metrics which were mapped into four broad themes, incorporating caseloads either directly as unadjusted counts (n= 11), nested in occupancy (n= 14), including additional factors (e.g., resource needs, speed of occupancy;n= 10), or using indirect proxies (e.g., altered staffing ratios, alternative care settings;n= 4). Notwithstanding metric heterogeneity, 32 of 39 studies (82%) reported detrimental adjusted odds/hazard ratio for caseload surge–mortality outcomes, reporting point estimates of up to four-fold increased risk of mortality. This signal persisted among study subgroups categorized by publication year, patient types, clinical settings, and country income status.

CONCLUSIONS:

Pandemic caseload surge was associated with lower survival across most studies regardless of jurisdiction, timing, and population. Markedly variable surge strain measures precluded meta-analysis and findings have uncertain generalizability to lower-middle-income countries (LMICs). These findings underscore the need for establishing a consensus surge metric that is sensitive to capturing harms in everyday fluctuations and future pandemics and is scalable to LMICs.
Initial Experience with Unidirectional Barbed Suture for Abdominal Donor Site Closure in Deep Inferior Epigastric Perforator Flap Breast Reconstruction
Authors: Finkelstein Emily R. , Ali Abdel-Moneim Mohamed , Holton Tripp , Slavin Benjamin , Taghioff Susan , Mella-Catinchi Juan , Singh Devinder
Published: March 2024

Background:

The deep inferior epigastric perforator (DIEP) flap is a predominant technique for autologous breast reconstruction. However, the best method of abdominal fascial closure in this technique is not well defined. This study details our initial experience with unidirectional barbed suture–only repair of abdominal donor site fascia.

Methods:

Patients who underwent DIEP flap breast reconstruction and abdominal fascial closure with Stratafix Symmetric Polydioxanone PDS Plus were retrospectively reviewed. Information regarding pertinent patient history, medical comorbidities, risk factors, and surgical technique was extracted, along with the incidence of eight separate postoperative abdominal surgical site occurrences.

Results:

Retrospective review identified 43 patients who underwent 19 unilateral and 24 bilateral DIEP flap breast reconstruction procedures (n = 67). Average patient follow-up was 791 days (range 153–1769). Six patients (14%) had a complication of the donor site. Seroma was most frequent (n = 3, 7%), followed by surgical site infection (n = 2, 5%). One patient had incisional dehiscence (2%) and another patient developed bulging (2%). No patients had chronic pain, weakness, hematoma, or hernia postoperatively. Patients with donor site complications had a history of abdominal/pelvic surgery significantly more often than the patients without donor site complications (100% versus 49%; P = 0.032).

Conclusions:

Abdominal fascial repair with Stratafix Symmetric suture alone led to low rates of abdominal donor site morbidity, including no hernia and rare bulging, following DIEP flap breast reconstruction. Additional advantages of this technique may be reduced operative times and lower operative costs compared with alternative methods of fascial repair, although prospective and randomized studies are warranted.
Low Dose Radiation and Solid Tumors Mortality Risk
Authors: Tao Xuguang (Grant) , Curriero Frank C. , Mahesh Mahadevappa
Published: March 2024

Background

US nuclear capable shipyard workers have increased potential for occupational radiation exposure.

Objective

The aim of the study is to examine solid tumor mortality risks at low doses.

Method

437,937 workers working from 1957 to 2004 at eight US shipyards were studied.

Results

Radiation workers with a median life-time dose at 0.82 mSv had a significantly lower solid tumor mortality risk (relative risk [RR]: 0.96, 95% confidence interval [CI]: 0.94–0.98) than nonradiation workers. Among 153,930 radiation workers, the RRs of solid tumors increased with increasing dose categories without statistical significance. The dose category >0–<25 mSv had significantly lower RR (0.95, 95% CI: 0.91–0.99) versus 0 dose and the excess relative risk was 0.05/100 mSv (95% CI: 0.01–0.08).

Conclusions

Solid tumor risk might increase with radiation dose, but not linearly at low doses. Actual mortality risk may be dependent on dose received.
Posttraumatic Stress Symptoms and Predictors Among Spanish Police and Armed Forces During the COVID-19 Pandemic in Spain
Authors: Gracia-Lanchares Susana , Garrido-Hernansaiz Helena , Bueno-Guerra Nereida , Rodríguez-Rey Rocío
Published: March 2024

Objective

To assess the psychological impact of the COVID-19 crisis on the police and armed forces.

Methods

Participants (N = 242) completed an online survey that assessed posttraumatic stress symptoms (PTSS), burnout, emotional suppression, and labor and sociodemographic variables. Mean difference, correlation, and stepwise linear regression tests were performed.

Results

One-third of participants showed severe PTSS, linked to patrolling duties, very frequent contact with other people, fear of contagion, perceived pandemic severity, living with at-risk people, taking a COVID-19 test, working more than normal, suffering an assault, having little vacation, and having to distance from loved ones. PTSS also correlated with the burnout dimensions and emotional suppression. Three-quarters had not received any support from their workplace.

Conclusions

Effective interventions to optimize these professionals’ personal, social, and working conditions are needed.
Circulating 25-hydroxyvitamin D concentration can predict bowel resection risk among individuals with inflammatory bowel disease in a longitudinal cohort with 13 years of follow-up
Authors: Dan Lintao , Wang Sidan , Chen Xuejie , Sun Yuhao , Fu Tian , Deng Minzi , Chen Jie , Du Zhongyan , Wang Xiaoyan
Published: March 2024

Background:

Although the beneficial properties of vitamin D in anti-inflammation and immunity-modulation are promising in the management of inflammatory bowel disease (IBD), data were limited for the critical IBD prognosis. The association between serum vitamin D levels and the risk of bowel resection in individuals with IBD remains largely unknown.

Materials and Methods:

The authors performed a longitudinal cohort study among 5474 individuals with IBD in the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] was measured using direct competitive chemiluminescent immunoassay. Bowel resection events were ascertained via national inpatient data. Multivariable-adjusted Cox proportional hazard regression was used to examine the association between serum 25(OH)D and bowel resection risk, presented with hazard ratios (HRs) and 95% CIs. Restricted cubic spline (RCS) was used to evaluate dose-response associations.

Results:

During a mean follow-up of 13.1 years, the authors documented 513 incident bowel resection cases. Compared to participants with vitamin D deficiency, nondeficient participants showed a significantly reduced bowel resection risk in IBD (HR 0.72, 95% CI: 0.59–0.87, P=0.001), Crohn’s disease (CD, HR 0.74, 95% CI: 0.56–0.98, P=0.038), and ulcerative colitis (UC, HR 0.73, 95% CI: 0.57–0.95, P=0.020). When comparing extreme quintiles of 25(OH)D level, participants with IBD showed a 34% reduced risk of bowel resection (95% CI: 11–51%, P=0.007) and participants with UC showed a 46% reduced risk (95% CI: 19–64%, P=0.003), while this association was not significant in CD (HR 0.93, 95% CI: 0.59–1.45, P=0.740). Linear dose-response associations were observed using the RCS curve (all P-nonlinearity>0.05).

Conclusion:

Increased serum level of 25(OH)D is independently associated with reduced bowel resection risk in IBD. This association was significant in UC but may not be stable in CD. Vitamin D deficiency is a risk factor for bowel resection in individuals with IBD, and may be an effective metric in predicting and risk-screening surgical events.
Savings in social expenditures for work incapacity in patients with inflammatory bowel disease depend on access to innovative therapies in Poland
Authors: Zagórowicz Edyta , Binowski Grzegorz , Strządała Dominik , Pruszko Cezary , Kucha Piotr , Reguła Jarosław
Published: March 2024

Objectives

Inflammatory bowel diseases (IBD) are an increasing burden for societies. We examined Polish Social Insurance Institution (ZUS) work incapacity expenditures for people with IBD compared with the general population.

Methods

Aggregate data were obtained on ZUS expenditures between 2012 and 2021 in Polish zlotys (PLN). Annual work incapacity benefit expenditures were analyzed and IBD benefit expenditures were examined relative to innovative IBD drug utilization in individual provinces.

Results

Between 2012 and 2021, annual ZUS expenditures per person increased, while expenditures per IBD patient decreased. Proportionally, absenteeism was the largest ZUS expenditure in the general population, while disability pensions were the largest in the IBD population. ZUS expenditures due to absenteeism in the general population increased by PLN 282 per person; those due to disability pensions decreased by PLN 85. Disability pension spending due to Crohn’s disease (CD) and ulcerative colitis (UC) decreased by PLN 371 and PLN 284, respectively, while absenteeism spending per person with CD and UC decreased (PLN 58 and PLN 35, respectively). Nationwide in 2021, 8.5% of people with CD and 1.9% of those with UC received innovative drugs. The percentage of people receiving innovative drugs and ZUS expenditure per person were inversely related in 9/16 provinces for CD and 5/16 for UC.

Conclusion

Polish state spending on work incapacity benefits increased in the general population but decreased in people with IBD between 2012 and 2021. Use of innovative drugs was associated with reduced spending per person with IBD in some provinces.
Metabolic dysfunction-associated steatotic liver disease-related hepatic fibrosis increases risk of insulin resistance, type 2 diabetes, and chronic kidney disease
Authors: Zhang Weijing , Song Wen Jing , Chen Weiyu , Pan Zoucheng , Zhang Jiawei , Fan Li , Li Jie
Published: March 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously called nonalcoholic fatty liver disease, NAFLD) is associated with cardiometabolic risk factors and chronic kidney disease (CKD). However, evidence is lacking regarding whether the severity of fibrosis is affected by these risk factors and diseases and to what degree. We aimed to determine the correlation between these factors and vibration-controlled transient elastography-determined liver stiffness measurements (LSMs) and controlled attenuation parameter (CAP) values in a sample of the US population. Data from the 2017–2018 cycle of the National Health and Nutrition Examination Survey were pooled. The association between LSM and cardiometabolic risk factors and CKD was assessed using generalized linear or logistic regression analyses. In multivariate regression analyses, CAP and BMI were adjusted as confounders. Of 3647 participants, 2079 (57.1%) had NAFLD/MASLD [weighted prevalence 54.8%; 95% confidence interval (CI) 51.8–57.9%]; the weighted prevalence of significant fibrosis (LSM ≥ 7.9 kPa) was 9.7% (95% CI 8.2–11.3%). Log LSM was associated with higher levels of homeostatic model assessment of insulin resistance (β = 2.19; P = 0.017), hepatic steatosis (CAP > 248 dB/m) [odds ratio (OR) 3.66; 95% CI 2.22–6.02], type 2 diabetes (OR 2.69; 95% CI 1.72–4.20), and CKD (OR 1.70; 95% CI 1.24–2.34). These correlations did not change notably after adjustments were made for waist circumference, CAP, and BMI. LSM and CAP, although influenced by waist circumference and BMI, are good indicators of hepatic fibrosis and steatosis. LSM is associated with insulin resistance, diabetes, and CKD independent of hepatic steatosis and obesity.
The Effect of ABCB1 and CES1 Polymorphisms on Plasma Levels of Dabigatran and Risk of Hemorrhagic Complications in Ischemic Stroke Patients
Authors: Anna Olšerová , Petr Janský , Hana Magerová , Tereza Šrámková , Petra Kešnerová , Silvia Kmetonyová , Vlastimil Šulc , Hana Halmová , Martin Šrámek , Ivana Šarbochová , Jaroslava Paulasová-Schwabová , Kateřina Benešová , Jan Macek , Václav Maťoška , Aleš Tomek
Published: March 2024

Background:

Dabigatran directly inhibits thrombin and is used in primary and secondary stroke prevention in individuals with nonvalvular atrial fibrillation. The prodrug dabigatran etexilate is absorbed by enteral P-glycoprotein (ABCB1) and then activated by hepatic and intestinal carboxylesterases (CES1) to produce active metabolites. Variations in dabigatran metabolism because of genetics may affect concentration levels and clinical outcomes.

Study Question:

We conducted a study to assess how polymorphisms in the CES1 (rs2244613) and ABCB1 (rs4148738) genes affect the through plasma level (cmin) of dabigatran and its correlation to clinical outcomes.

Study Design:

Retrospective multicentric study of consecutive patients on dabigatran therapy. Examination of CES1 rs2244613 and ABCB1 rs4148738 polymorphisms, cmin 12 hours after administration, clinical follow-up (ischemic stroke, major or clinically relevant hemorrhage, myocardial infarction, other thromboembolism, and death).

Measures and Outcomes:

A total of 432 patients received treatment for an average of 19.78 months (SD of 20.165). The sex distribution of the patients was 56.5% male, and the average age was 67.56 years (SD of 14.7). The ABCB1 variant genotype was present in 67.8% of patients, whereas 37.5% carried the CES1 polymorphism.

Results:

Compared with wild-type patients, patients with the CES1 variant had significantly lower dabigatran plasma levels (with a mean difference of 16.986; 95% confidence interval, 5.794–28.178 ng/mL, P = 0.003). We also found a significant risk of major bleeding in patients carrying the ABCB1 rs4148738 allele (hazard ratio = 1.99, confidence interval 95% 1.10 to 3.59, P = 0.024).

Conclusions:

The CES1 variant genotype rs2244613 is closely linked with reduced cmin of dabigatran. Carriers of the ABCB1 rs4148738 polymorphism exhibit a tendency toward higher plasma levels of dabigatran, which leads to a significantly increased risk of bleeding.
Melanoma—Modern Treatment for Metastatic Melanoma
Authors: Dimitrova Maya , Weber Jeffrey
Published: March 2024

Traditional chemotherapy has been ineffective in the treatment of metastatic melanoma. Until the use of checkpoint inhibitors, patients had very limited survival. Since the original US Food and Drug Administration approval of ipilimumab over a decade ago, the armamentarium of immunotherapeutic agents has expanded to include programmed cell death protein 1 and lymphocyte activation gene 3 antibodies, requiring a nuanced approach to the selection of frontline treatments, managing patients through recurrence and progression, and determining length of therapy. Herein, we review the existing evidence supporting current standard immunotherapy regimens and discuss the clinical decision-making involved in treating patients with metastatic melanoma with checkpoint inhibitors.
The Impact of Radiation on Nipple Symmetry After Bilateral Nipple-Sparing Mastectomy and Implant-Based Reconstruction
Authors: Brown Ciara A. , Carlson Grant W.
Published: March 2024

Introduction

Radiation therapy can adversely affect outcomes of implant-based breast reconstruction, potentially complicating procedures like nipple-sparing mastectomy (NSM), which is increasingly popular in breast cancer management. This study aims to evaluate the impact of radiation on nipple symmetry in patients undergoing bilateral NSM with implant-based reconstruction.

Methods

We conducted a retrospective analysis using data from an Emory University review board-approved database. This encompassed bilateral NSMs coupled with immediate implant-based reconstructions. The BCCT.core software was employed to objectively measure nipple asymmetry preoperatively and postoperatively. Metrics, such as Breast Retraction Assessment values, upper nipple retraction, lower breast contour, and nipple to midline (NML) discrepancies were quantified. The study included 80 patients with a minimum of 1 year of follow-up; among them, 15 received radiation therapy (RT) while 65 did not.

Results

The reconstructions were divided into tissue expander, used in 39 cases (48.8%), and direct-to-implant (DTI), employed in 41 cases (51.2%). The DTIs were further categorized based on the location of the implant: 22 subpectoral and 19 prepectoral. Radiation was applied to 15 breasts, distributed among prepectoral DTI (4), subpectoral DTI (6), and tissue expander (5). Breast Retraction Assessment scores significantly differed between the nonirradiated and irradiated groups (1.49 vs 2.64, P < 0.0004). Nipple to midline differences and Upper Nipple Retraction also significantly varied postradiation, especially when comparing subpectoral and prepectoral implant placements.

Conclusions

Radiation therapy has a detrimental effect on nipple symmetry after bilateral NSM and implant-based reconstruction, with variations seen regardless of the implant's placement or the reconstructive technique utilized. Specifically, subpectoral reconstructions irradiated were prone to lateral nipple displacement, likely related to radiation-induced pectoralis muscle changes, while prepectoral irradiated reconstructions tended to have increased vertical displacement. These insights are crucial for patient education and surgical planning in the context of radiation and breast reconstruction.
ImageAssist
Authors: Golinko Michael S. , Abou-Ghanem Odette , Simard Michael , Caudill Mike , Pontell Matthew E. , O’Sick Nick , Oglesby Brandon , Arrieta Mark
Published: March 2024

Statement of the Problem

Standardized medical photography of the face is a vital part of patient documentation, clinical evaluation, and scholarly dissemination. Because digital photography is a mainstay in clinical care, there is a critical need for an easy-to-use mobile device application that could assist users in taking a standardized clinical photograph. ImageAssist was developed to answer this need. The mobile application is integrated into the electronic medical record (EMR); it implements and automates American Society of Plastic Surgery/Plastic Surgery Research Foundation photographic guidelines with background deletion.

Initial Product Development

A team consisting of a craniofacial plastic surgeon and the Health Information Technology product group developed and implemented the pilot application of ImageAssist. The application launches directly from patients' chart in the mobile version of the EMR, EPIC Haiku (Verona, Wisconsin). Standard views of the face (90-degree, oblique left and right, front and basal view) were built into digital templates and are user selected. Red digital frames overlay the patients' face on the screen and turn green once standardized alignment is achieved, prompting the user to capture. The background is then digitally subtracted to a standard blue, and the photograph is not stored on the user's phone.

Early User experience

ImageAssist initial beta user group was limited to 13 providers across dermatology, ENT, and plastic surgery. A mix of physicians, advanced practice providers, and nurses was included to pilot the application in the outpatient clinic setting using Image Assist on their smart phone. After using the app, an internal survey was used to gain feedback on the user experience. In the first 2 years of use, 31 users have taken more than 3400 photographs in more than 800 clinical encounters. Since initial release, automated background deletion also has been functional for any anatomic area.

Conclusions

ImageAssist is a novel smartphone application that standardizes clinical photography and integrated into the EMR, which could save both time and expense for clinicians seeking to take consistent clinical images. Future steps include continued refinement of current image capture functionality and development of a stand-alone mobile device application.
ChatGPT in Urogynecology Research: Novel or Not?
Authors: Choueka David , Tabakin Alexandra L. , Shalom Dara F.
Published: March 2024

Importance

ChatGPT (Chat Generative Pre-trained Transformer) is an artificial intelligence (AI) chatbot that provides human-like responses to text prompts. Little is known regarding ChatGPT’s ability to identify original research ideas in urogynecology.

Objective

Our objective was to evaluate the accuracy of ChatGPT in generating novel systematic review (SR) and research ideas in urogynecology.

Study Design

In this cross-sectional study, we asked ChatGPT to generate 10 novel SR ideas that have not yet been published for each of the following 5 topics: (1) urogynecology, (2) tension-free vaginal tape slings, (3) pessaries for pelvic organ prolapse, (4) beta-3 agonist use for overactive bladder, and (5) sexual function with genitourinary syndrome of menopause. Research idea novelty was assessed by cross-referencing PubMed and Scopus to determine if any prior publications existed.

Results

ChatGPT proposed 50 total SR ideas, including 10 for each prompt. Overall, ChatGPT showed 54% overall accuracy in developing novel SR ideas. Nonnovel SR ideas had a median of 19 (interquartile range, 8–35) published SRs on the suggested topic. When stratified by prompt type, 50% of general and 40–70% of specific urogynecology proposed SR ideas were found to be novel. There were no publications of any type identified for 7 of the 50 suggested ideas.

Conclusions

ChatGPT may be helpful for identifying novel research ideas in urogynecology, but its accuracy is limited. It is essential for those using ChatGPT to review existing literature to ensure originality and credibility. As AI transforms health care, we encourage all urogynecologists to familiarize themselves with popular AI platforms.
Electroacupuncture promotes macrophage/microglial M2 polarization and suppresses inflammatory pain through AMPK
Authors: Nan Fu-Bei , Gu Yi-Xiao , Wang Jun-Lu , Chen Shuang-Dong
Published: March 2024

Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture’s antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5‘-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture’s analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture’s facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture’s antinociceptive effect through the promotion of M2 macrophage/microglial polarization.
Role of LGL1 in cerebellar primordium of embryonic mice
Authors: Hou Congzhe , Zhang Aizhen , Jin Yecheng , Ye Chao , Li Runze , Liu Zhenhua , Gao Jiangang
Published: March 2024

Lethal giant larvae 1 (LGL1) is originally recognized as a tumor suppressor, implicated in maintaining cell polarity in Drosophila and mammalian cells. Cell polarity plays a crucial role in tumorigenesis. We previously established Pax2-LGL1−/− conditional knockout mice but did not focus on the tumorigenesis in cerebellar primordium. HE staining was used to detect the morphological structure of the cerebellar primordium during early embryonic development in Pax2-LGL1−/− mice. Immunofluorescence assays were used to detect the expression of polar molecules. TUNEL staining assessed tissue apoptosis. Our findings reveal that deletion of LGL1 leads to the emergence of neuroblastoma-like tissues within the cerebellum primordium during early embryogenesis. This outcome can be attributed to alterations in expression patterns of polar molecules Cdc42 and β-catenin following early deletion of LGL1, resulting in loss of cell polarity among neuroepithelial cells and subsequent formation of tumor-like tissues. However, further histological examination demonstrated that these tumor-like tissues disappear from embryonic day 15.5 onwards within the cerebellar primordium of Pax2-LGL1−/− mice due to apoptosis-mediated cellular compensation. Our data emphasize the importance of LGL1 in maintaining neuroepithelial cell polarity and reveal a novel role for LGL1 in regulating tumorigenesis and ablation in the cerebellar primordium.
Cosmic mysteries and the hydrogen 21-cm line: bridging the gap with lunar observations
Authors: Fialkov A. , Gessey-Jones T. , Dhandha J.
Published: March 2024

The hydrogen 21-cm signal is predicted to be the richest probe of the young Universe, including those eras known as the cosmic Dark Ages, the Cosmic Dawn (when the first star and black hole formed) and the Epoch of Reionization. This signal holds the key to deciphering processes that take place at the early stages of cosmic history. In this opinion piece, we discuss the potential scientific merit of lunar observations of the 21-cm signal and their advantages over more affordable terrestrial efforts. The Moon is a prime location for radio cosmology which will enable precision observations of the low-frequency radio sky. The uniqueness of such observations is that they will provide an unparalleled opportunity to test cosmology and the nature of dark matter using the Dark Ages 21-cm signal. No less enticing is the opportunity to obtain a much clearer picture of the Cosmic Dawn than that currently achievable from the ground, which will allow us to determine the properties of the first stars and black holes.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 2)’.
Improving Diagnostic Precision: Urine Proteomics Identifies Promising Biomarkers for Necrotizing Enterocolitis
Authors: Mackay Stephen , Frazer Lauren C. , Bailey Grace K. , Miller Claire M. , Gong Qingqing , DeWitt Olivia N. , Good Misty
Published: March 2024

Background

Necrotizing enterocolitis (NEC) is a severe intestinal disease that primarily impacts preterm infants. Current diagnostic tools are inadequate, so urine proteomics was performed for patients with and without NEC to identify putative biomarkers.

Research design and methods

The abundance of urinary proteins detected using an aptamer-based microarray was compared for infants with NEC (n=20) and controls, age-matched (n=8) or self-matched (n=12). Spearmanrcorrelation and hierarchical cluster analysis were performed. The area under the curve (AUC) was calculated for receiver operator characteristic curves (ROC).

Results

Ninety-nine proteins differed in NEC vs. controls based on median fold change (Log2± 1.1) and significance (P< 0.05). Patterns of abundance were consistent for both types of matching, and samples clustered based on NEC severity. Two panels were built to differentiate between infants with and without NEC. Panel 1 included proteins associated with inflammation/NEC and produced by the intestinal epithelium (REG1B, REG3A, FABP2, DEFA5, AUC 0.90). Panel 2 consisted of proteins with the largest fold change between NEC vs. controls and the highest individual AUC values (REG1B, SSBP1, CRYZL1, ITM2B, IL36B, IL36RN, AUC 0.98).

Conclusions

Urine proteins significantly differ between infants with and without NEC, which supports their potential as future biomarkers.

Graphical abstract.Overview of study findings. Created with Biorender.com
Navigating primary health care challenges: Insights from older people with multimorbidity in Malawi
Authors: Kwaitana Duncan , Bates Maya Jane , Msowoya Esnath , Breevoort Dorothee van , Mildestvedt Thomas , Meland Eivind , Umar Eric
Published: March 2024

The global population is undergoing a significant surge in aging leading to increased susceptibility to various forms of progressive illnesses. This phenomenon significantly impacts both individual health and healthcare systems. Low and Middle Income Countries face particular challenges, as their Primary Health Care (PHC) settings often lack the necessary human and material resources to effectively address the escalating healthcare demands of the older people. This study set out to explore the experiences of older people living with progressive multimorbidity in accessing PHC services in Malawi. Between July 2022 and January 2023, a total of sixty in-depth interviews were conducted with dyads of individuals aged ≥50 years and their caregivers, and twelve healthcare workers in three public hospitals across Malawi’s three administrative regions. The study employed a stratified selection of sites, ensuring representation from rural, peri-urban, and urban settings, allowing for a comprehensive comparison of diverse perspectives. Guided by the Andersen-Newman theoretical framework, the study assessed the barriers, facilitators, and need factors influencing PHC service utilization by the older people. Three themes, consistent across all sites emerged, encompassing barriers, facilitators, and need factors respectively. The themes include: (1) clinic environment: inconvenient clinic setup, reliable PHC services and research in diabetic foods; (2) geographical factors: bad road conditions, lack of comprehensive PHC at local health facility and need for community approaches; and (3) social factors: encompassing use of alternative medicine, transport support, perceived health care benefit and support with startup capital for small-scale businesses. This research highlights the impact of multiple factors on the access to and utilization of PHC services among older individuals, emphasizing the urgent need for enhanced nationwide availability of such services. It strongly recommends a thorough investigation into successful practices implemented in diverse health facilities in Malawi, with a specific focus on addressing the unique healthcare needs of the older population.
OnSIDES (ON-label SIDE effectS resource) Database : Extracting Adverse Drug Events from Drug Labels using Natural Language Processing Models
Authors: Tanaka Yutaro , Chen Hsin Yi , Belloni Pietro , Gisladottir Undina , Kefeli Jenna , Patterson Jason , Srinivasan Apoorva , Zietz Michael , Sirdeshmukh Gaurav , Berkowitz Jacob , Brown Kathleen LaRow , Tatonetti Nicholas P.
Published: March 2024

Adverse drug events (ADEs) are the fourth leading cause of death in the US and cost billions of dollars annually in increased healthcare costs. However, few machine-readable databases of ADEs exist, limiting the opportunity to study drug safety on a broader, systematic scale. Recent advances in Natural Language Processing methods, such as BERT models, present an opportunity to accurately extract relevant information from unstructured biomedical text. As such, we fine-tuned a PubMedBERT model to extract ADE terms from descriptive text in FDA Structured Product Labels for prescription drugs. With this model, we achieve an F1 score of 0.90, AUROC of 0.92, and AUPR of 0.95 at extracting ADEs from the labels’ “Adverse Reactions”. We further utilize this method to extract serious ADEs from labels’ “Boxed Warnings”, and ADEs specifically noted for pediatric patients. Here, we present OnSIDES (ON-label SIDE effectS resource), a compiled, computable database of drug-ADE pairs generated with this method. OnSIDES contains more than 3.6 million drug-ADE pairs for 3,233 unique drug ingredient combinations extracted from 47,211 labels. Additionally, we expand this method to extract ADEs from drug labels of other major nations/regions - Japan, the UK, and the EU - to build a complementary OnSIDES-INTL database. To present potential applications, we used OnSIDES to predict novel drug targets and indications, analyze enrichment of ADEs across drug classes, and predict novel ADEs from chemical compound structures. We conclude that OnSIDES can be utilized as a comprehensive resource to study and enhance drug safety.

One Sentence Summary

OnSIDES is a large, comprehensive database of adverse drug events extracted from drug labels using natural language processing methods.
Evaluating the Portability of SepsisWatch: A Multi-Site External Validation of a Sepsis Machine Learning Model
Authors: Valan Bruno , Prakash Anusha , Ratliff William , Gao Michael , Muthya Srikanth , Thomas Ajit , Eaton Jennifer L. , Gardner Matt , Nichols Marshall , Revoir Mike , Tart Dustin , O’Brien Cara , Patel Manesh , Balu Suresh , Sendak Mark
Published: March 2024

Importance

Sepsis accounts for a substantial portion of global deaths and healthcare costs. Early detection using machine learning (ML) models offers a critical opportunity to improve care and reduce the burden of sepsis.

Objective

To externally validate the SepsisWatch ML model, initially developed at Duke University, in a community healthcare and assess its performance and clinical utility in early sepsis detection.

Design

This retrospective external validation study evaluated the performance of the SepsisWatch model in a new environment. Data from patient encounters at Summa Health’s emergency departments between 2020 and 2021 were used. The study analyzed the model’s ability to predict sepsis using a combination of static and dynamic patient data.

Setting

The study was conducted at Summa Health, a nonprofit healthcare system in Northeast Ohio, covering two emergency departments (EDs) associated with acute care hospitals, and two standalone EDs.

Participants

Encounters associated with adult patients in any of Summa Health’s four EDs were included. Encounters lasting <1 hour were excluded. Only the first 36 hours of each encounter were used in model evaluation.

Intervention(s)/Exposure(s)

The SepsisWatch model was used to predict sepsis based on patient data.

Main Outcome(s) and Measure(s)

The primary outcomes measured were the model’s area under the precision-recall curve (AUPRC), and area under the receiver operator curve (AUROC).

Results

The study included 205,005 encounters from 101,584 unique patients. 54.7% (n = 112,223) patients were female and the mean age was 50 (IQR, [38,71]). The model demonstrated strong performance across the Summa Health system, with little variation across different sites. The AUROC ranged from 0.906 to 0.960, and the AUPRC ranged from 0.177 to 0.252 across the four sites.

Conclusions and Relevance

The external validation of the SepsisWatch model in a community health system setting confirmed its robust performance and portability across different geographical and demographic contexts. The study underscores the potential of advanced ML models in improving sepsis detection in both academic and community hospital settings, paving the way for prospective studies to measure the clinical and operational impact of such models in healthcare.
Cold and dense perturbative QCD in a very strong magnetic background
Authors: Fraga Eduardo S. , Palhares Letícia F. , Restrepo Tulio E.
Published: March 2024

We compute the pressure from first principles within perturbative QCD at finite baryon density and very high magnetic fields up to two-loops and with physical quark masses. The region of validity for our framework is given by ms≪μq≪eB, where ms is the strange quark mass, μq is the quark chemical potential, e is the fundamental electric charge, and B is the magnetic field strength. We include the effects of the renormalization scale in the running coupling, αs(μq,eB), and running strange quark mass. We also discuss the simplifications that come about in the chiral limit. The effectively negligible contribution of the exchange diagram allows for building a simple analytic model for the equation of state for pure quark magnetars and computing their mass and radius at very large values of B. These results provide constraints on the behavior of the maximum mass and associated radius from perturbative QCD. We also discuss the magnetic bag model for extreme magnetic fields.

Published by the American Physical Society
2024
Benchmark calculations of fully heavy compact and molecular tetraquark states
Authors: Wu Wei-Lin , Chen Yan-Ke , Meng Lu , Zhu Shi-Lin
Published: March 2024

We calculate the mass spectrum of the S-wave fully heavy tetraquark systems QQQ¯Q¯(Q=c,b) with both normal (JPC=0++,1+−,2++) and exotic (JPC=0+−,1++,2+−) C-parities using three different quark potential models (AL1, AP1, BGS). The exotic C-parity systems refer to the ones that cannot be composed of two S-wave ground heavy quarkonia. We incorporate the molecular dimeson and compact diquark-antidiquark spatial correlations simultaneously, thereby discerning the actual configurations of the states. We employ the Gaussian expansion method to solve the four-body Schrödinger equation, and the complex scaling method to identify the resonant states. The mass spectra in three different models qualitatively agree with each other. We obtain several resonant states with JPC=0++,1+−,2++,1++ in the mass region (6.92,7.30) GeV, some of which are good candidates of the experimentally observed X(6900) and X(7200). We also obtain several exotic C-parity zero-width states with JPC=0+− and 2+−. These zero-width states have no corresponding S-wave diquarkonium threshold and can only decay strongly to final states with P-wave quarkonia. With the notation T4Q,J(C)(M), we deduce from the root mean square radii that the X(7200) candidates T4c,0(+)(7173),T4c,2(+)(7214) and the state T4c,1(−)(7191) look like molecular states although most of the resonant and zero-width states are compact states.

Published by the American Physical Society
2024
Amplifying nonresonant production of dark sector particles in scattering dominance regime
Authors: Du Mingxuan , Liu Jia , Wang Xiao-Ping , Wu Tianhao
Published: March 2024

We investigate the enhancement of dark sector particle production within the scattering dominant regime. These particles typically exhibit a slight mixing with Standard Model particles through various portals, allowing for their generation through in-medium oscillation from Standard Model particle sources. Our analysis reveals that in the scattering dominance regime, with a significantly smaller scattering mean free path λsca compared to the absorption mean free path λabs, the nonresonant production of sterile states can experience an enhancement by a factor of λabs/λsca. This phenomenon is demonstrated within the context of kinetic mixing dark photon production at a reactor, precisely satisfying this condition. By incorporating this collisional enhancement, we find that the current sensitivity to the mixing parameter ε for dark photons in the TEXONO experiment can be significantly improved across a range spanning from tens of eV to MeV. This advancement establishes the most stringent laboratory constraint within this mass spectrum for the dark photon. Sterile neutrino production, however, does not exhibit such enhancement, either due to the failure to meet the scattering dominance criterion or the neutrino damping in resonant production.

Published by the American Physical Society
2024