bluuebunny/crossref_metadata_2025 huggingface dataset:
Base editing correction of OCRL in Lowe syndrome: ABE-mediated functional rescue in patient-derived fibroblasts
Authors: Chen Siyu , Lo Chien-Hui , Liu Zhiquan , Wang Qing , Ning Ke , Li Tingting , Sun Yang
Published: April 2024

Lowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P. There are no effective targeted treatments for Lowe syndrome. Here, we demonstrate a novel gene therapy for Lowe syndrome in patient fibroblasts using an adenine base editor (ABE) that can efficiently correct pathogenic point mutations. We show that ABE8e-NG-based correction of a disease-causing mutation in a Lowe patient-derived fibroblast line containing R844X mutation in OCRL gene, restores OCRL expression at mRNA and protein levels. It also restores cellular abnormalities that are hallmarks of OCRL dysfunction, including defects in ciliogenesis, microtubule anchoring, α-actinin distribution, and F-actin network. The study indicates that ABE-mediated gene therapy is a feasible treatment for Lowe syndrome, laying the foundation for therapeutic application of ABE in the currently incurable disease.
Naringin Alleviates Intestinal Fibrosis by Inhibiting ER Stress–Induced PAR2 Activation
Authors: Liu Jinguo , Xu Lei , Wang Li , Wang Qianqian , Yu Liangliang , Zhang Shuo
Published: April 2024

Fibrosis characterized by intestinal strictures is a common complication of Crohn’s disease (CD), without specific antifibrotic drugs, which usually relies on surgical intervention. The transcription factor XBP1, a key component of endoplasmic reticulum (ER) stress, is required for degranulation of mast cells and linked to PAR2 activation and fibrosis. Many studies have confirmed that naringin (NAR) can inhibit ER stress and reduce organ fibrosis. We hypothesized that ER stress activated the PAR2-induced epithelial-mesenchymal transition process by stimulating mast cell degranulation to release tryptase and led to intestinal fibrosis in CD patients; NAR might play an antifibrotic role by inhibiting ER stress–induced PAR2 activation. We report that the expression levels of XBP1, mast cell tryptase, and PAR2 are upregulated in fibrotic strictures of CD patients. Molecular docking simulates the interaction of NAR and spliced XBP1. ER stress stimulates degranulation of mast cells to secrete tryptase, activates PAR2-induced epithelial-mesenchymal transition process, and promotes intestinal fibrosis in vitro and vivo experiments, which is inhibited by NAR. Moreover, F2rl1 (the coding gene of PAR2) deletion in intestinal epithelial cells decreases the antifibrotic effect of NAR. Hence, the ER stress–mast cell tryptase–PAR2 axis can promote intestinal fibrosis, and NAR administration can alleviate intestinal fibrosis by inhibiting ER stress–induced PAR2 activation.
Bending the Automation Bias Curve: A Study of Human and AI-Based Decision Making in National Security Contexts
Authors: Horowitz Michael C , Kahn Lauren
Published: April 2024

Uses of artificial intelligence (AI) are growing around the world. What will influence AI adoption in the international security realm? Research on automation bias suggests that humans can often be overconfident in AI, whereas research on algorithm aversion shows that, as the stakes of a decision rise, humans become more cautious about trusting algorithms. We theorize about the relationship between background knowledge about AI, trust in AI, and how these interact with other factors to influence the probability of automation bias in the international security context. We test these in a preregistered task identification experiment across a representative sample of 9,000 adults in nine countries with varying levels of AI industries. The results strongly support the theory, especially concerning AI background knowledge. A version of the Dunning–Kruger effect appears to be at play, whereby those with the lowest level of experience with AI are slightly more likely to be algorithm-averse, then automation bias occurs at lower levels of knowledge before leveling off as a respondent’s AI background reaches the highest levels. Additional results show effects from the task’s difficulty, overall AI trust, and whether a human or AI decision aid is described as highly competent or less competent.
Catching Fire: How National Humiliation Spreads Hostile Foreign Policy Preferences on Chinese Social Media
Authors: Masterson Michael
Published: April 2024

Research shows that emotions alter preferences, which are central to many models of political choice. However, how can theories that explain individual-level preference change explain policy outcomes, which usually take place at higher levels of analysis? I outline three competing approaches to this question, ultimately building on the third approach, which argues that emotions can spread through emotional contagion within identity groups. This implies emotions can broadly shift preferences towards or away from conflict during crises. It also explains how identities, which are relatively constant over the medium term, can suddenly become fault lines in a conflict. I find supporting evidence using a large (more than 1.6 billion posts) nationally representative data set of Chinese social media posts. Users’ national humiliation posts lead their followers to become more likely to make posts about national humiliation, suggesting contagion, and about using military force and maintaining territorial disputes, suggesting preference change.
Analysis of ester-producing performance in high-yield ethyl hexanoate yeast and the effect on metabolites in bio- enhanced Daqu, the starter for Baijiu and other traditional fermented foods
Authors: Zhao He , Du Binghao , Zhao Pengju , Chen Xi , Zhao Jingrong , Wu Qiuhua , Zhu Lining , Ma Huifeng , Sun Baoguo , Min Weihong , Li Xiuting
Published: April 2024

Aims

Ethyl hexanoate, one of the key flavor compounds in strong-flavor Baijiu. To improve the content of ethyl hexanoate in strong-flavor Baijiu, a functional strain with high yield of ethyl hexanoate was screened and its ester-producing performance was studied.

Methods and results

Upon identification, the strain was classified as Candida sp. and designated as ZY002. Under optimal fermentation conditions, the content of ethyl hexanoate synthesized by ZY002 can be as high as 170.56 mg L−1. A fermentation test was carried out using the ZY002 strain bioaugmented Daqu to verify the role of the strain applied to Baijiu brewing. It was found that strain ZY002 could not only improve the moisture and alcohol contents of fermented grains but also diminish the presence of reducing sugar and crude starch. Furthermore, it notably amplified the abundance of flavor compounds.

Conclusion

In this study, Candida sp. ZY002 with a high yield of ethyl hexanoate provided high-quality strain resources for the actual industrial production of Baijiu.
The standardized ileal digestible lysine-to-net energy ratio in the diets of sows to optimize milk nitrogen retention is dynamic during lactation
Authors: Watzeck Madelaine C , Huber Lee-Anne
Published: April 2024

Fifty-two multiparous sows (average parity 3.1 ± 0.9 and initial BW 245.6 ± 32.5 kg) were used to evaluate the effects of dietary standardized ileal digestible (SID) Lys-to-net energy (NE) ratios on nitrogen (N) utilization throughout a 24-d lactation period. Sows were randomly assigned to one of five isoenergetic feeding programs that provided equally spaced and increasing SID Lys-to-NE ratios between 2.79 and 5.50 g SID Lys/Mcal NE. The feeding programs were generated by blending the two extreme diets in varying proportions and were provided to sows immediately after farrowing (day 1) and until weaning at day 24 ± 1. Nitrogen balances were conducted between days 4 and 7, 12 and 15, and 20 and 23 ± 1 of lactation to represent weeks 1, 2, and 3, respectively, using total urine collection and fecal grab sampling. Contrast statements were used to determine the linear and quadratic effects of increasing Lys-to-NE ratios. Linear and quadratic broken-line and polynomial quadratic (QPM) models were used to determine the optimum dietary Lys-to-NE ratios for N retention in milk. The Bayesian information criterion was used to assess the best fit. Feeding program did not influence sow average daily feed intake (5.8 ± 0.1 kg), BW change (−8.2 ± 3.1 kg), or change in back fat thickness (−2.6 ± 0.7 mm) over the 24-d lactation period, but piglet average daily gain increased with dietary SID Lys-to-NE ratio (linear; P < 0.05). Sow N intake increased with increasing dietary Lys-to-NE ratio in weeks 2 and 3 (linear; P < 0.001). Whole-body N retention (N intake − N output in urine and feces) increased with increasing dietary Lys-to-NE ratio in all weeks (linear; P < 0.05). The N retention in milk tended to increase then decrease with increasing dietary Lys-to-NE ratio in weeks 1 and 2 (quadratic; P = 0.051 and P = 0.081) and the QPM showed optimal milk N retention at 4.28, 4.42, and 4.67 g Lys/Mcal NE for weeks 1, 2, and 3, respectively. Maternal N retention (N intake − N output in urine, feces, and milk) decreased and then increased in week 1 (quadratic; P < 0.01) and increased in weeks 2 and 3 (linear; P < 0.01) with increasing dietary Lys-to-NE ratio. Therefore, the SID Lys-to-NE ratio necessary to optimize milk N output is dynamic throughout lactation. A two-diet feeding program could be created to match optimal weekly or daily SID Lys-to-NE ratios, which could lead to improved piglet ADG and body weights at weaning.
Absenteeism, Productivity, and Relational Contracts Inside the Firm
Authors: Adhvaryu Achyuta , Gauthier Jean-François , Nyshadham Anant , Tamayo Jorge
Published: April 2024

We study relational contracts among managers using unique data that tracks transfers of workers across teams in Indian ready-made garment factories. We focus on how relational contracts help managers cope with worker absenteeism shocks, which are frequent, often large, weakly correlated across teams, and which substantially reduce team productivity. Together these facts imply gains from sharing workers. We show that managers respond to shocks by lending and borrowing workers in a manner consistent with relational contracting, but many potentially beneficial transfers are unrealized. This is because managers’ primary relationships are with a very small subset of potential partners. A borrowing event studies around main trading partners’ separations from the firm reinforces the importance of relationships. We show robustness to excluding worker moves least likely to reflect relational borrowing responses to idiosyncratic absenteeism shocks. Counterfactual simulations reveal large gains to reducing costs associated with forming and maintaining additional relationships among managers.
Three Arguments Against Institutional Conscientious Objection, and Why They Are (Metaphysically) Unconvincing
Authors: Symons Xavier , Chua Reginald Mary
Published: April 2024

The past decade has seen a burgeoning of scholarly interest in conscientious objection in healthcare. While the literature to date has focused primarily on individual healthcare practitioners who object to participation in morally controversial procedures, in this article we consider a different albeit related issue, namely, whether publicly funded healthcare institutions should be required to provide morally controversial services such as abortions, emergency contraception, voluntary sterilizations, and voluntary euthanasia. Substantive debates about institutional responsibility have remained largely at the level of first-order ethical debate over medical practices which institutions have refused to offer; in this article, we argue that more fundamental questions about the metaphysics of institutions provide a neglected avenue for understanding the basis of institutional conscientious objection. To do so, we articulate a metaphysical model of institutional conscience, and consider three well-known arguments for undermining institutional conscientious objection in light of this model. We show how our metaphysical analysis of institutions creates difficulties for justifying sanctions on institutions that conscientiously object. Thus, we argue, questions about the metaphysics of institutions are deserving of serious attention from both critics and defenders of institutional conscientious objection.
Feeling our place in the world: an active inference account of self-esteem
Authors: Albarracin Mahault , Bouchard-Joly Gabriel , Sheikhbahaee Zahra , Miller Mark , Pitliya Riddhi J , Poirier Pierre
Published: April 2024

Self-esteem, the evaluation of one’s own worth or value, is a critical aspect of psychological well-being and mental health. In this paper, we propose an active inference account of self-esteem, casting it as a sociometer or an inferential capacity to interpret one’s standing within a social group. This approach allows us to explore the interaction between an individual’s self-perception and the expectations of their social environment.When there is a mismatch between these perceptions and expectations, the individual needs to adjust their actions or update their self-perception to better align with their current experiences. We also consider this hypothesis in relation with recent research on affective inference, suggesting that self-esteem enables the individual to track and respond to this discrepancy through affective states such as anxiety or positive affect. By acting as an inferential sociometer, self-esteem allows individuals to navigate and adapt to their social environment, ultimately impacting their psychological well-being and mental health.
Candida spp. Deep Sternal Wound Infections: A Consequence of Antibiotic use?
Authors: McNeil Thomas , Coats Joanna , Daniel Santhosh , Gordon David
Published: April 2024

A cluster of deep sternal wound infections caused by Candida spp. occurred at our institution. Investigation did not disclose a common environmental source. We postulate that broad-spectrum antibiotic surgical prophylaxis and liberal use of antibiotics contributed to these infections.
Are DNA Repair Gene Alterations Associated With the Response to Platinum-Based Regimen and Immune Checkpoint Inhibitors in Patients With Solid Tumors?
Authors: Chabot Clément , Italiano Antoine , Crombé Amandine , Soubeyran Isabelle , Laizet Yech’an , Khalifa Emmanuel , Cousin Sophie
Published: April 2024

We analyzed the antitumor activity of platinum-based chemotherapies and then immune checkpoint inhibitors (ICI) in all-comers patients with solid tumors having a somatic DNA damage repair gene alteration (DDR-GA) identified through a prospective precision medicine study (NCT02534649). Each DDR-GA was classified as pathogenic (Pa), probably pathogenic (PPa), and unknown pathogenicity (UPa) according to OncoKB and ClinVAR databases. Between January 2018 and May 2020, 662 patients were screened. One hundred ninety-nine tumors with DDR-GA were found in 121 (18.3%) patients. Ninety-six patients received platinum-based chemotherapy in the advanced setting. No difference in objective response rate (ORR) under platinum regimen was observed between the 3 DDR-GA groups. The only predictor of worse progression-free survival (PFS) in Cox regression was the existence of a Pa alteration compared to the UPa group: HR = 2.11 (95% CI = 1.2-3.7), P = .009. Forty-eight patients received ICI alone or in combination. We observed a significant trend in better ORR to ICI according to the DDR-GA status: 1/11 (9%) patients in UPa, 5/17 (29.4%) patients in PPa, and 9/20 (45%) patients in Pa (P = .003, Cochran-Armitage trend test), and an increased 6-month PFS probability of 11%, 44%, and 50% in the UPa, PPa, and Pa groups, respectively (P = .37, log-rank test). Overall, somatic pathogenic DDR-GAs were not associated with ORR or PFS to platinum-based chemotherapy in patients with unselected advanced solid tumors. However, DDR-GA seemed to impact ORR and PFS to ICI, paving the way for a therapeutic combination with ICI and molecules targeting the DDR mechanisms, which are currently evaluated in ongoing clinical trials.
Storage, Disposal, and Use of Opioids Among Cancer Patients in Central China: A Multi-Center Cross-Sectional Study
Authors: Zhang Mi , Chen Huili , Luo Chenxi , Wang Xuanxuan , Liu Liang , Wu Dongfang , Cheng Hong
Published: April 2024

Objective

Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear.

Methods

A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids.

Results

The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (OR = 4.57, P = .0423), had a history of alcohol use (OR = 1.91, P = .0399), and used opioids other than morphine (OR = 2.31, P = .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor’s degree or above were less likely to dispose of (OR = 0.36, P = .0261) and use (OR = 0.31, P = .0127) opioids unsafely.

Conclusion

A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug “take-back” initiatives to improve opioid-related practices.
Natural disasters as a public health issue
Authors: Maboloc Christopher Ryan
Published: April 2024

This paper explains why natural disasters are a public health issue. A case in point is the Masara landslide in Maco Town, the Philippines. Public health concerns are not just the physical but also the ‘total well-being of persons’. Classifying natural calamities as a concern related to public health will give a sense of urgency on the matter and thereby encourage governments to act on the negative effects of climate change, especially in developing countries.
Evolution of exploitation and replication of giant viruses and virophages
Authors: del Arco Ana , Fischer Matthias G , Becks Lutz
Published: April 2024

Tripartite biotic interactions are inherently complex, and the strong interdependence of species and often one-sided exploitation can make these systems vulnerable to extinction. The persistence of species depends then on the balance between exploitation and avoidance of exploitation beyond the point where sustainable resource use is no longer possible. We used this general prediction to test the potential role of trait evolution for persistence in a tripartite microbial system consisting of a marine heterotrophic flagellate preyed upon by a giant virus, which in turn is parasitized by a virophage. Host and virophage may benefit from this interaction because the virophage reduces the harmful effects of the giant virus on the host population and the virophage can persist integrated into the host genome when giant viruses are scarce. We grew hosts and virus in the presence and absence of the virophage over ∼280 host generations and tested whether levels of exploitation and replication in the giant virus and/or virophage population evolved over the course of the experiment, and whether the changes were such that they could avoid overexploitation and extinction. We found that the giant virus evolved toward lower levels of replication and the virophage evolved toward increased replication but decreased exploitation of the giant virus. These changes reduced overall host exploitation by the virus and virus exploitation by the virophage and are predicted to facilitate persistence.
Circadian disturbances by altering the light–dark cycle negatively affects hematopoietic function of bone marrow in mice
Authors: Yang Honglian , Zhao Guojie , Lu Yue , Ma Kefeng , Gao Xiujie , She Xiaojun , Zhu Yingwen , Wang Kun , Du Lianqun , Wang Ying , Xi Zhuge , Cui Bo
Published: April 2024

Circadian rhythms in metabolically active tissues are crucial for maintaining physical health. Circadian disturbance (CD) can cause various health issues, such as metabolic abnormalities and immune and cognitive dysfunctions. However, studies on the role of CD in immune cell development and differentiation, as well as the rhythmic expression of the core clock genes and their altered expression under CD, remain unclear. Therefore, we exposed C57bl/6j mice to repeated reversed light–dark cycles for 90 days to research the effects of CD on bone marrow (BM) hematopoietic function. We also researched the effects of CD on endogenous circadian rhythms, temporally dependent expression in peripheral blood and myeloid leukocytes, environmental homeostasis within BM, and circadian oscillations of hematopoietic–extrinsic cues. Our results confirmed that when the light and dark cycles around mice were frequently reversed, the circadian rhythmic expression of the two main circadian rhythm markers, the hypothalamic clock gene, and serum melatonin, was disturbed, indicating that the body was in a state of endogenous CD. Furthermore, CD altered the temporally dependent expression of peripheral blood and BM leukocytes and destroyed environmental homeostasis within the BM as well as circadian oscillations of hematopoietic–extrinsic cues, which may negatively affect BM hematopoiesis in mice. Collectively, these results demonstrate that circadian rhythms are vital for maintaining health and suggest that the association between CD and hematopoietic dysfunction warrants further investigation.
Beyond the Procedure Log: Using Individualized Learning Plans to Set Learner-Specific Milestones for Procedural Skills Acquisition
Authors: Dyster Timothy , Santhosh Lekshmi
Published: April 2024

Procedural training for nonsurgical fields, such as internal medicine, is an important component of medical education. However, recent changes to accreditation guidelines have resulted in less formal guidance on procedural competency, not only leading to opportunities for individualizing training but also creating potential problems for trainees and training programs. In this article, the authors use internal medicine as an exemplar to review current strategies for procedural education in nonsurgical fields, including procedural simulation, dedicated procedural rotations, and advanced subspecialty training, and highlight an emerging need for learner-specific terminal milestones in procedural training. Individualized learning plans (ILPs), collections of trainee-specific objectives for learning, are arguably a useful strategy for organizing procedural training. The role of ILPs as a framework to support setting learner-specific terminal milestones, guide skill acquisition, and allocate procedural learning opportunities based on trainees’ anticipated career plans is subsequently explored, and how an ILP-based approach might be implemented within the complex educational milieu of a clinical training program is examined. The limitations and pitfalls of an ILP-based approach, including the need for development of coaching programs, are considered. The authors conclude that, despite the limitations of ILPs, when combined with other current strategies for building trainees’ procedural competence, these plans may help trainees maximize the educational benefits of their training period and can encourage effective, safer, and equitable allocation of procedural practice opportunities.
Systems-Based Practice in Graduate Medical Education: Evolving Toward an Ideal Future State
Authors: Bhate Tahara D. , Sukhera Javeed , Litwin Sasha , Chan Teresa M. , Wong Brian M. , Smeraglio Andrea
Published: April 2024

Systems-based practice (SBP) was first introduced as a core competency in graduate medical education (GME) in 2002 by the Accreditation Council for Graduate Medical Education as part of the Outcomes Project. While inclusion of SBP content in GME has become increasingly common, there have also been well-documented stumbling blocks, including perceptions that SBP has eroded the amount of curricular time available for more medically focused competencies, is not relevant for some practice contexts, and is not introduced early enough in training. As a result, SBP learning experiences often feel disconnected from medical trainees’ practical reality. In this commentary, the authors provide guidance regarding potential changes that may facilitate the evolution of SBP toward an ideal future state where graduates bring a systems science mindset to all aspects of their work. Specific suggestions include the following: (1) expanding the SBP toolbox to reflect current-day health system needs, (2) evolve the teaching methodology, (3) broadening the scope of relevant SBP content areas, and (4) emphasizing SBP as an integrated responsibility for all health care team members. Levers to enact this transformation exist and must be used to influence change at the learner, faculty, program, and clinical learning environment levels.

Physicians operate within an increasingly complex health care system that highlights the intersection of health care with complex social, environmental, and relational contexts. Consequently, the role of SBP in both physician work responsibilities and educational requirements continues to expand. To meet this growing demand, GME must adapt how it supports and trains the next generation of systems thinkers, ensuring they understand how levers in the health care system directly affect health outcomes for their patients, and integrate SBP into the foundation of GME curricula in an inclusive, holistic, and unrestrained way.
Preoperative Hounsfield Units Predict Pedicle Screw Loosening in Osteoporotic Patients Following Short-Segment Lumbar Fusion
Authors: Narayanan Rajkishen , Tarawneh Omar H. , Trenchfield Delano , Meade Matthew H. , Lee Yunsoo , Opara Olivia , McCurdy Michael A. , Pineda Nathaniel , Kaye lan D. , Alhassan Fatimah , Vo Michael , Mangan John J. , Canseco Jose A. , Hilibrand Alan S. , Vaccaro Alexander R. , Kepler Christopher K. , Schroeder Gregory D.
Published: April 2024

Study Design.

Retrospective Cohort.

Objective.

(1) To determine if vertebral HU values obtained from preoperative CT predict postoperative outcomes following one to three level lumbar fusion and (2) to investigate whether decreased BMD values determined by HU predict cage subsidence and screw loosening.

Summary of Background Data.

In light of suboptimal screening for osteoporosis, vertebral computerized tomography (CT) Hounsfield Units (HU), have been investigated as a surrogate for bone mineral density (BMD).

Materials and Methods.

In this retrospective study, adult patients who underwent one to three level posterior lumbar decompression and fusion (PLDF) or transforaminal lumbar interbody and fusion (TLIF) for degenerative disease between the years 2017 and 2022 were eligible for inclusion. Demographics and surgical characteristics were collected. Outcomes assessed included 90-day readmissions, 90-day complications, revisions, patient-reported outcomes (PROMs), cage subsidence, and screw loosening. Osteoporosis was defined as HU of ≤110 on preoperative CT at L1.

Results.

We assessed 119 patients with a mean age of 59.1, of whom 80.7% were white and 64.7% were nonsmokers. The majority underwent PLDF (63%) compared with TLIF (37%), with an average of 1.63 levels fused. Osteoporosis was diagnosed in 37.8% of the cohort with a mean HU in the osteoporotic group of 88.4 compared with 169 in nonosteoporotic patients. Although older in age, osteoporotic individuals did not exhibit increased 90-day readmissions, complications, or revisions compared with nonosteoporotic patients. A significant increase in the incidence of screw loosening was noted in the osteoporotic group with no differences observed in subsidence rates. On multivariable linear regression osteoporosis was independently associated with less improvement in visual analog scale (VAS) scores for back pain.

Conclusions.

Osteoporosis predicts screw loosening and increased back pain. Clinicians should be advised of the importance of preoperative BMD optimization as part of their surgical planning and the utility of vertebral CT HU as a tool for risk stratification.

Level of Evidence.

3.
Pyruvate Kinase M2: A Potential Regulator of Cardiac Injury Through Glycolytic and Non-glycolytic Pathways
Authors: Zeng Chenxin , Wu Jiangfeng , Li Junming
Published: April 2024

Adult animals are unable to regenerate heart cells due to postnatal cardiomyocyte cycle arrest, leading to higher mortality rates in cardiomyopathy. However, reprogramming of energy metabolism in cardiomyocytes provides a new perspective on the contribution of glycolysis to repair, regeneration, and fibrosis after cardiac injury. Pyruvate kinase (PK) is a key enzyme in the glycolysis process. This review focuses on the glycolysis function of PKM2, although PKM1 and PKM2 both play significant roles in the process after cardiac injury. PKM2 exists in both low-activity dimer and high-activity tetramer forms. PKM2 dimers promote aerobic glycolysis but have low catalytic activity, leading to the accumulation of glycolytic intermediates. These intermediates enter the pentose phosphate pathway to promote cardiomyocyte proliferation and heart regeneration. Additionally, they activate adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, protecting the heart against ischemic damage. PKM2 tetramers function similar to PKM1 in glycolysis, promoting pyruvate oxidation and subsequently ATP generation to protect the heart from ischemic damage. They also activate KDM5 through the accumulation of αKG, thereby promoting cardiomyocyte proliferation and cardiac regeneration. Apart from glycolysis, PKM2 interacts with transcription factors like Jmjd4, RAC1, β-catenin, and hypoxia-inducible factor (HIF)-1α, playing various roles in homeostasis maintenance, remodeling, survival regulation, and neovascularization promotion. However, PKM2 has also been implicated in promoting cardiac fibrosis through mechanisms like sirtuin (SIRT) 3 deletion, TG2 expression enhancement, and activation of transforming growth factor-β1 (TGF-β1)/Smad2/3 and Jak2/Stat3 signals. Overall, PKM2 shows promising potential as a therapeutic target for promoting cardiomyocyte proliferation and cardiac regeneration and addressing cardiac fibrosis after injury.
Rapidly Growing Congenital Disseminated Pyogenic Granuloma in the Scalp Treated with Staged Embolization and Excision: A Case Report
Authors: Mohnasky Michael , Wood Jeyhan , Nieman Elizabeth , Brondon Jennifer , Khan Kamran , Kim Kyung Rae
Published: April 2024

Pyogenic granulomas are common, acquired vascular lesions that most often arise spontaneously or in sites of previous trauma. However, there are reports of a few cases that describe a rare condition, congenital disseminated pyogenic granuloma (CDPG), in which an infant either is born with or shortly after birth develops multiple pyogenic granulomas. A hallmark of CDPG is negative staining for glucose transporter 1 (GLUT-1) on immunohistochemistry, which helps distinguish it from the more common multifocal infantile hemangiomas. Because few case reports have described CDPG, much is unknown about its characteristics, clinical course, and most effective treatment options. Here, we present a case of an infant with a unique presentation of CDPG with lesions that are atypically large and growing at a rapid pace. We also describe a novel approach to treating large pyogenic granulomas in CDPG via staged glue embolization and surgical excision.
Anatomical and Hemodynamic Characterization of Totally Artificial Hearts
Authors: Monreal Gretel , Koenig Steven C. , Huang Jiapeng , Slaughter Mark S.
Published: April 2024

We characterize the anatomy and function of never before studied total artificial hearts (TAHs) using established methods for testing mechanical circulatory support (MCS) devices. A historical review of TAHs is also presented to aid in benchmarking performance metrics. Six TAHs, ranging from spooky Halloween beating hearts to a cute colorful plush heart, were imaged, instrumented (mock flow loops) to measure their pressure, volume, and flow, and qualitatively evaluated by 3rd party cardiac surgeons for anatomical accuracy and surgical considerations. Imaging of Claw, Beating, and Frankenstein TAHs revealed internal motors, circuit boards, and speakers. Gummy TAH was ranked favorite TAH for tactile realism, while Frankenstein TAH had the most favorable audible/visual indicators, including an illuminated Jacob’s Ladder. Beating TAH demonstrated superior pulsatile hemodynamic performance compared to Claw TAH (16mL vs 1.3mL stroke volume). Light Up TAH and Gummy TAH functioned only as passive compliance chambers. Cute TAH rapidly exsanguinated due to its porosity (-3.0 L/min flow). These TAHs demonstrated a wide range of anatomical accuracy, surgeon appeal, unique features, and hemodynamic performance. While Claw TAH and Beating TAH successfully generated a modicum of pulsatility, we recommend the clinical community continue to support pre-clinical development of emerging or use of clinically-approved TAHs.
Introduction of Western Medicines into China and Improvement on Decoctions during Modern China
Authors: Zhu Ruisi
Published: April 2024

During the late Qing dynasty (1840 A.D.-1912 A.D.), a large quantity of Western medicines entered China, which continuously impacted the traditional Chinese medicine (TCM) market and revealed the shortcomings of Chinese medicines. Some personages in the TCM community followed the trend of learning from the West, and attempted to reform TCM, with the improvement on decoction becoming an important aspect of this effort. Through debates and trials, the improvement on decoction underwent three stages of conceptual evolution: “taking Chinese medicines as the foundation and referring to the dosage forms of Western medicines”, “introducing Western techniques to serve the preparation of decoctions” and “integrating the theories of TCM and Western medicine to improve decoctions”. The study on the improvement on decoction highlights the effective complementarity between modern TCM and Western medicine in the field of pharmacy, and provides valuable experience and support for the reevaluation of the value of TCM in contemporary society.
Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology
Authors: Li Peizhe , Tai Yuxing , Zhang Long , Wang Sixian , Guan Qifan , Li Xin , Liu Shaowei , Liu Mingjun
Published: April 2024

This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.
The Role of Epstein–Barr Virus (EBV) Infected Gastric Cancer in Increasing microRNA124 (miR-124) Promoter Methylation and Enhancer of Zeste Homolog 2 (EZH2) Gene Expression
Authors: Ghoreshi Zohreh-Al-Sadat , Rezaei Zadeh Rukerd Mohammad , Askarpour Hedyeh , Kheirkhah Vakilabad Ali Asghar , Nakhaie Mohsen , Abbaszadeh Afshar Mohammad Javad , Behboudi Emad , Charostad Javad , Arefinia Nasir
Published: April 2024

The tumor suppressor microRNAs, miR-21, miR-124, and miR-494, participate in the controlling several cellular processes. To assess target miRNAs promoter methylation levels, we investigated 304 pairs of gastric cancer (GC) tissues and non-tumor tissues. We used a commercial real-time polymerase chain reaction (RT-PCR) for Epstein-Barr virus (EBV) and Helicobacter pylori kit to detect EBV and H. pylori DNA in GC tissues. After finding hypermethylation in the promoter of the miR-124 gene, we evaluated its expression level using quantitative PCR (qPCR). Bioinformatics analysis confirmed miR-124 as a target of enhancer of Zeste homolog 2 (EZH2). Additionally, qPCR confirmed the association between EZH2 and miR-124. EBV and H. pylori DNA were detected in 9.5% and 15.1% of GC patients, respectively. Our findings also revealed significant differences in the miR-124 methylation levels among EBV-infected GC patients, H. pylori infected GC patients, GC patients without EBV and H. pylori infection, and non-tumor tissue. Bioinformatics and qPCR assays suggested an inverse relationship between the expression levels of EZH2 and miR-124 in EBV-infected GC patients. Our data revealed hypermethylation of the miR-124 promoter and significant reduction in its expression in EBV-infected GC tissues. It is possible that miR-124 may target EZH2 by binding to the 3’-UTR of the EZH2 gene, thus potentially contributing to the development of EBV-infected GC.
Autoimmune hemolytic anemia and thrombocytopenia in a Chinese patient with heterozygous NBAS mutations: Case report
Authors: Yang Yuanlin , Fei Xiaoming , Lei Fang , Wang Lixia , Yu Xianqiu , Tang Yu
Published: April 2024

Rationale:

Neuroblastoma amplified sequence (NBAS)-associated disease is an autosomal recessive disorder and a broad spectrum of clinical symptoms has been reported. However, autoimmune mediated hemolytic anemia (AIHA) is rarely reported in NBAS disease.

Patient concerns:

A now 21-year-old male harbors heterozygous variants of c.6840G>A and c.335 + 1G>A and was found had retarded growth, hypogammaglobulinemia, B lymphopenia, optic atrophy, horizontal nystagmus, slight splenomegaly and hepatomegaly since childhood. This case had normal hemoglobin level and platelet count in his childhood. He developed AIHA first in his adulthood and then thrombocytopenia during the treatment of AIHA. The mechanism underlying a case with pronounced hypogammaglobulinemia and B lymphopenia is elusive. In addition to biallelic NBAS mutations, a germline mutation in the ANKRD26 (c.2356C>T) gene was also detected. So either autoimmune or ANKRD26 mutation-mediated thrombocytopenia is possible in this case.

Intervention and outcome:

He was initially managed with steroid and intermittent intravenous immunoglobulin supplement. After treatment, he responded well with a normalization of hemoglobin and serum bilirubin. But the patient subsequently experienced severe thrombocytopenia in addition to AIHA. He was then given daily avatrombopag in addition to steroid escalation. He responded again to new treatment, with the hemoglobin levels and platelet counts went back to the normal ranges. Now he was on de-escalated weekly avatrombopag and low-dose steroids maintenance.

Conclusion:

The phenotype of this case indicates that c.335 + 1G>A NBAS variant is probably a pathogenic one and c.2356C>T ANKRD26 variant is improbably a pathogenic one. AIHA may respond well to steroid even when happened in patients with NBAS disease.
Investigating acupoint selection and combinations of acupuncture for primary idiopathic tinnitus using data mining
Authors: Huang Liangliang , Fan Yushan , Lin Rui , Zhao Yiping , Mo Yaru , Luo Sen , Li Zhan
Published: April 2024

Background:

Acupuncture is widely used in the treatment of tinnitus worldwide because of its good efficacy and safety. However, the criteria for selecting acupoint prescriptions and combinations have not been summarized. Therefore, data mining was used herein to determine the treatment principles and the most effective acupoint selection for the treatment of idiopathic tinnitus.

Methods:

The clinical research literature of acupuncture in the treatment of idiopathic tinnitus from the establishment of the database to September 1, 2023 in China National Knowledge Infrastructure, China Medical Journal Full-text Database, PubMed, Embase, Cochrane Library and Web of Science databases was retrieved and extracted. Microsoft Excel 2016 was used to establish the acupoint prescription database and the frequency statistics of acupoints, meridians and specific acupoints were carried out. IBM SPSS Statistics 25.0 software was used for cluster analysis of acupoints, and IBM SPSS Modeler18.0 software was used for association rule analysis of acupoints.

Results:

A total of 112 articles were included, involving 221 acupuncture prescriptions, including 99 acupoints, with a total frequency of 1786 times. The 5 most frequently used acupoints were Tinggong (SI19), Tinghui (GB2), Yifeng (TE17), Ermen (TE21), and Zhongzhu (TE3). The commonly used meridians were Sanjiao meridian of hand-shaoyang, Gallbladder meridian of foot-shaoyang and Small intestine meridian of hand-taiyang. The specific points are mostly Crossing point, Five-shu point and Yuan-primary point. The core acupoint combination of association rules was Ermen (TE21)–Tinggong (SI19)–Tinghui (GB2)–Yifeng (TE17), and 3 effective clustering groups were obtained by cluster analysis of high-frequency acupoints.

Conclusion:

In this study, the published literature on acupuncture treatment of idiopathic tinnitus was analyzed by data mining, and the relationship between acupoints was explored, which provided a more wise choice for clinical acupuncture treatment of idiopathic tinnitus.
Acute Helicobacter pylori infection prevalence and association with metabolic abnormality in general Chinese population: A retrospective study
Authors: Feng Zhan , Chen Lan , Wu Qing , Xu Fan , Tong Qian , Wang Guofu
Published: April 2024

Helicobacter pylori (H pylori) infection was common worldwide and previous researches on the correlation between H pylori infection and metabolic abnormality provided inconsistent conclusions. We assessed acute H pylori infection prevalence and the relationship with metabolic abnormality in general Chinese population. Participants attending for the physical examination underwent a carbon-13 urea breath test. For individual, the following data were collected: age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, total protein, albumin, globulin (GLB), total bilirubin, direct bilirubin (DBIL), indirect bilirubin, alanine transaminase, glutamyl transpeptidase, alkaline phosphatase, cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, urea nitrogen, creatinine, uric acid, fasting plasma glucose (FPG), and homocysteine. A total of 29,154 participants were enrolled. The prevalence of acute H pylori infection was 29.79% (8684/29,154). Spearson correlation analysis showed that gender, BMI, ALB, GLB, total bilirubin, DBIL, indirect bilirubin, and FPG were closely related to H pylori infection. Multinomial logistic regressions analysis with stepwise subset selection further identified gender, BMI, ALB, GLB, DBIL, and FPG as independent risk factors for acute H pylori infection. Our results indicated that acute H pylori infection might has a significant impact on metabolic abnormalities, which should be further confirmed.
Efficacy and safety of Chinese patent medicine in the adjuvant treatment of prostate cancer: A Bayesian network meta-analysis
Authors: Wang Shiheng , Zhang Fengxia , Liu Jianfeng , Qin Peijie
Published: April 2024

Background:

Prostate cancer is the most common cancer in men. In China, traditional Chinese medicine is used to treat prostate cancer. However, there is a lack of evidence for differences in the effectiveness and safety of different Chinese patent medicines. Therefore, we conducted this Network Meta-analysis to investigate the efficacy and safety of different Chinese patent medicines in the treatment of prostate cancer.

Methods:

We systematically search PubMed, Web of Science, Embase, Cochrane library, CNKI database, VIP database, wanfang database, and SinoMed Randomized controlled trials of Chinese patent medicines for the treatment of prostate cancer sores included in the database were retrieved until June 1, 2023. The included studies were assessed for risk of bias using Cochrane randomized controlled trial Bias risk Assessment tool. The main outcome indicators were Efficacy, Prostate Specific Antigen, and adverse reaction. Since different courses of treatment were used in the included studies, we used Bayesian mesh meta-regression to investigate the effects of treatment courses on efficacy and safety.

Results:

Twenty-seven articles were included, involving 1885 patients. Including 9 kinds of Chinese patent medicine. The results of Network Meta-analysis show that: ① efficacy: compared with androgen antagonists, Bruceolic oil emulsion (relative risk = 1.70, 95% credibility interval [CI] (1.30, 2.29)), Compound Kushen injection (relative risk = 1.39, 95%CI (1.19, 1.70)) had significant advantages. There was no significant difference among all Chinese patent medicines (P > .05). The top 3 Chinese patent medicines were Bruceolic oil emulsion, Zhibodihuang pill, Compound Kushen injection. ② Prostate specific antigen: compared with androgen antagonists, Bruceolic oil emulsion (mean difference [MD] = −10.4, 95%CI [−17.6, −3.21]), Compound Kushen injection (MD = −4.46, 95%CI [−8.80, −1.70]), Shenfu injection (MD = −14.7, 95%CI [−23.4, −6.01]) had significant advantages. The top 3 Chinese patent medicines were Shenfu injection, Bruceolic oil emulsion, Compound Kushen injection. adverse reaction: compared with androgen antagonists, there was no significant difference among all PCM (P > .05).

Conclusion:

Compared with androgen antagonists, Chinese patent medicine has significant difference in effectiveness. The effect of Chinese patent medicine is little affected by the course of treatment and dose. From comprehensive analysis, Bruceolic oil emulsion combined with androgen antagonist is the best intervention measures.