bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of the circRNA-miRNA-mRNA axis based on ferroptosis-related gene AKR1C1 to explore the potential pathogenesis of abdominal aortic aneurysm
Authors: Huang Xuehua , Deng Huanhuan
Published: June 2024

Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains unclear and its treatment is limited to surgical treatment. With the deepening and analysis of studies on the mechanism of ferroptosis, a new idea has been provided for the clinical management of AAA patients, including diagnosis, treatment and prevention. Therefore, this paper aims to construct a competitive endogenous RNA (ceRNA) regulatory axis based on ferroptosis to preliminarily explore the pathogenesis and potential therapeutic targets of AAA. We obtained upregulated and downregulated ferroptosis-related DEGs (FRGs) from GSE144431 dataset and 60 known ferroptosis-related genes. Pearson correlation analysis was used to find aldoketone reductase 1C (AKR1C1) in AAA samples. Enrichment analysis of these genes was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlation test between immune cells and AKR1C1 was investigated through single-sample gene set enrichment analysis (ssGSEA). The AKR1C1-miRNA pairs were predicted by the TargetScan database and miRWalk database. Circular RNA (CircRNA)-miRNA pairs were selected by the CircInteractome database. Overlapping miRNA between circRNA-miRNA and AKR1C1-miRNA pairs was visualized by Venn diagram. Finally, the circRNA-miRNA-mRNA axis was constructed by searching for upstream circRNA and downstream mRNA of overlapping miRNA. Only one downregulated AKR1C1 gene was found in GSE144431 and 60 ferroptosis-related genes. Functional Enrichment and Pathway Analysis of AKR1C1-related genes were further explored, and it was observed that they were mainly enriched in “response to oxidative stress,” “glutathione biosynthetic process” and “nonribosomal peptide biosynthetic process,” “Ferroptosis,” “Glutathione metabolism” and “Chemical carcinogenesis-reactive oxygen species.” They were also found to be significantly associated with most immune cells, including Activated Dendritic cells, CD56dim Natural killer cells, Gamma Delta T cells, Immature B cells, Plasmacytoid dendritic cell, Type 2 T helper cell, Activated CD4 T cell and Type 1 T helper cell. Has_circ_0005073-miRNA-543 and AKR1C1-miRNA-543 were identified by Online Database analysis. Therefore, we have established the has_circ_0005073/miRNA-543/AKR1C1 axis in AAA. We found AKR1C1 was differentially expressed between normal and AAA groups. Based on AKR1C1, we constructed the has_circ_0005073/miRNA-543/AKR1C1 axis to analyze AAA.
Association between the red cell distribution width and mortality in elderly patients with non-traumatic coma: An observational cohort study
Authors: Kim Dongki , Lee Donghun , Lee Jiho , Lee Byungkook , Ko Sang Won
Published: June 2024

Elevated red blood cell distribution width (RDW) can be associated with disease severity. However, studies on RDW for the prognosis of elderly patients with non-traumatic coma (NTC) are lacking. This study aims to examine the relationship between RDW and outcomes in elderly patients with NTC. This observational cohort study included elderly patients (aged ≥ 65 years) with NTC between January 2022 and December 2022. We measured RDW upon patient arrival at the emergency department (ED). We conducted a multivariable analysis using logistic regression of relevant covariates to predict in-hospital mortality. Survival curves based on 30-day mortality were designed using the Kaplan–Meier method. The primary outcome was in-hospital mortality, and the secondary outcome was 30-day mortality. A total of 689 patients were included in the study, and in-hospital mortality was 29.6% (n = 204). Our results found that the RDWs of non-survivors were significantly greater than those of survivors (14.6% vs 13.6%). Multivariable analysis showed that RDWs at ED arrival were independently associated with in-hospital mortality (odds ratio, 1.126; 95% confidence interval, 1.047–1.212; P < .001). The Kaplan–Meier curve indicated that the survival probability of patients with a low RDW was greater than those with a high RDW. Having a high RDW at ED arrival was associated with in-hospital mortality in elderly patients with NTC.
Characteristics and Clinical Value of MYC, BCL2, and BCL6 Rearrangement Detected by Next-generation Sequencing in DLBCL
Authors: Zeng Yupeng , Wei Ran , Bao Longlong , Xue Tian , Qin Yulan , Ren Min , Bai Qianming , Yao Qianlan , Yu Chengli , Chen Chen , Wei Ping , Yu Baohua , Cao Junning , Li Xiaoqiu , Zhang Qunling , Zhou Xiaoyan
Published: June 2024

MYC, BCL2, and BCL6 rearrangements are clinically important events of diffuse large B-cell lymphoma (DLBCL). The ability and clinical value of targeted next-generation sequencing (NGS) in the detection of these rearrangements in DLBCL have not been fully determined. We performed targeted NGS (481-gene-panel) and break-apart FISH of MYC, BCL2, and BCL6 gene regions in 233 DLBCL cases. We identified 88 rearrangements (16 MYC; 20 BCL2; 52 BCL6 ) using NGS and 96 rearrangements (28 MYC; 20 BCL2; 65 BCL6) using FISH. The consistency rates between FISH and targeted NGS for the detection of MYC, BCL2, and BCL6 rearrangements were 93%, 97%, and 89%, respectively. FISH-cryptic rearrangements (NGS+/FISH−) were detected in 7 cases (1 MYC; 3 BCL2; 2 BCL6; 1 MYC::BCL6), mainly caused by small chromosomal insertions and inversions. NGS−/FISH+ were detected in 38 cases (14 MYC; 4 BCL2; 20 BCL6).To clarify the cause of the inconsistencies, we selected 17 from the NGS−/FISH+ rearrangements for further whole genome sequencing (WGS), and all 17 rearrangements were detected with break points by WGS. These break points were all located outside the region covered by the probe of targeted NGS, and most (16/17) were located in the intergenic region. These results indicated that targeted NGS is a powerful clinical diagnostics tool for comprehensive MYC, BCL2, and BCL6 rearrangement detection. Compared to FISH, it has advantages in describing the break point distribution, identifying uncharacterized partners, and detecting FISH-cryptic rearrangements. However, the lack of high-sensitivity caused by insufficient probe coverage is the main limitation of the current technology.
Intra-ampullary Papillary Tubular Neoplasm (IAPN)
Authors: Tarcan Zeynep C. , Esmer Rohat , Akar Kadriye E. , Bagci Pelin , Bozkurtlar Emine , Saka Burcu , Armutlu Ayse , Sahin Ozkan Hulya , Ozcan Kerem , Taskin Orhun C. , Kapran Yersu , Aydin Mericoz Cisel , Balci Serdar , Yilmaz Serpil , Cengiz Duygu , Gurses Bengi , Alper Emrah , Tellioglu Gurkan , Bozkurt Emre , Bilge Orhan , Cheng Jeanette D. , Basturk Olca , Adsay N. Volkan
Published: June 2024

The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an “ampullary-duodenal tumor,” with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1 cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P=0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the “ampullary-ductal” carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).
Preferences for Management of Pediatric Pneumonia
Authors: Ramgopal Sriram , Belanger Thomas , Lorenz Douglas , Lipsett Susan C. , Neuman Mark I. , Liebovitz David , Florin Todd A.
Published: July 2024

Background

It is unknown which factors are associated with chest radiograph (CXR) and antibiotic use for suspected community-acquired pneumonia (CAP) in children. We evaluated factors associated with CXR and antibiotic preferences among clinicians for children with suspected CAP using case scenarios generated through artificial intelligence (AI).

Methods

We performed a survey of general pediatric, pediatric emergency medicine, and emergency medicine attending physicians employed by a private physician contractor. Respondents were given 5 unique, AI-generated case scenarios. We used generalized estimating equations to identify factors associated with CXR and antibiotic use. We evaluated the cluster-weighted correlation between clinician suspicion and clinical prediction model risk estimates for CAP using 2 predictive models.

Results

A total of 172 respondents provided responses to 839 scenarios. Factors associated with CXR acquisition (OR, [95% CI]) included presence of crackles (4.17 [2.19, 7.95]), prior pneumonia (2.38 [1.32, 4.20]), chest pain (1.90 [1.18, 3.05]) and fever (1.82 [1.32, 2.52]). The decision to use antibiotics before knowledge of CXR results included past hospitalization for pneumonia (4.24 [1.88, 9.57]), focal decreased breath sounds (3.86 [1.98, 7.52]), and crackles (3.45 [2.15, 5.53]). After revealing CXR results to clinicians, these results were the sole predictor associated with antibiotic decision-making. Suspicion for CAP correlated with one of 2 prediction models for CAP (Spearman's rho = 0.25). Factors associated with a greater suspicion of pneumonia included prior pneumonia, duration of illness, worsening course of illness, shortness of breath, vomiting, decreased oral intake or urinary output, respiratory distress, head nodding, focal decreased breath sounds, focal rhonchi, fever, and crackles, and lower pulse oximetry.

Conclusions

Ordering preferences for CXRs demonstrated similarities and differences with evidence-based risk models for CAP. Clinicians relied heavily on CXR findings to guide antibiotic ordering. These findings can be used within decision support systems to promote evidence-based management practices for pediatric CAP.
Hospital Patient Experience: Exploring Hospitals as Shifters and Sustainers Over Time
Authors: Hamadi Hanadi , Silvera Geoffrey A. , Park Sinyoung , Xu Jing , Xie Zhigang
Published: June 2024

Background and Objectives:

Patient experience is a key factor in measuring hospital performance, and the Hospital Consumer Assessment of Healthcare Providers and Systems survey tool is used to assess patient perceptions. Hospitals with positive patient experience tend to have a better quality of clinical care, lower readmission and mortality rates, and an overall shorter inpatient length of stay. Studies have identified several organizational determinants of high- and low-rated patient experiences, including hospital size, type, staffing levels, and patient demographics.

This study aims to explore the determinants of consistently high- and low-rated patient experience, as well as factors associated with positive and negative changes in patient experience over time.

Method:

The 2014 to 2019 American Hospital Association annual survey and the Centers for Medicare and Medicaid Services Hospital Value-Based Purchasing database were used. A total of 2801 acute-care hospitals were included in this study. A series of multivariate logistic regressions were used to model the probability of “1” (being a superior hospital or an inferior hospital). In addition, a generalized linear mixed model for binary responses was used to analyze the change (probability of positive and negative change).

Results:

The results showed that most hospitals did not sustain superior or inferior performance, and competition decreased the likelihood of a hospital consistently performing well in terms of patient experience. Superior performance was associated with hospital ownership (P< .001), size (P= .026), location (P= .002), teaching status (P= .009), average Herfindahl-Hirschman Index value (P= .005), and Medicaid and Medicare patient population. On the other hand, inferior performance was associated with hospital ownership (P= .003), size (P< .001), teaching status (P= .003), safety net status (P= .020), and Medicaid and Medicare patient population.

Conclusion:

This study aimed to examine the trends in hospital patient experience performance and the influence of hospital organizational characteristics on those trends. Our findings allow us to question the widely held belief that patient experience is a metric of differentiation and industry competition, suggesting that performance in this domain has not been utilized by most hospitals as a source of sustainable competitive advantage. The findings from this study highlight the importance of considering changes in performance over time and the need for significant organizational efforts to improve hospital performance in terms of patient experience.
An Analysis of Inpatient Satisfaction with Trust-related Factors of Public Secondary and Tertiary Hospitals in China
Authors: Yan Jingjing
Published: June 2024

Background and Objectives:

Patient satisfaction surveys are implemented as an essential quality improvement tool in healthcare markets. This study investigates patient satisfaction in public secondary and tertiary hospitals and identifies factors contributing to inpatient satisfaction, particularly trust-related factors, to eventually improve the quality of care in the healthcare system.

Methods:

A population-based cross-sectional survey was conducted between February and April 2021 in 31 Chinese provinces. Telephone interviews with computer assistance were used to gather data. Spearman Rank Correlation was used to analyze satisfaction with hospitalization services between secondary and tertiary hospitals. Multiple Linear Regression was used to determine the influencing factors of overall patient satisfaction.

Results:

Inpatients reported more satisfaction with inpatient care when doctors treated them respectfully (p < 0.01). Inpatients with higher self-identified social class reported higher satisfaction (p < 0.01). Inpatients who trust in most people in society (p < 0.01) and trust in the Chinese healthcare system (p < 0.01) reported higher satisfaction. Female inpatients reported higher overall satisfaction (p < 0.01).

Conclusions:

The study of Chinese inpatients in secondary and tertiary hospitals highlighted the importance of respect from doctors, their self-identified social class, and their trust in influencing satisfaction during their hospital stay and called for additional research into policy measures.
Remote Health Management via WeChat to Improve the Quality of Life of Patients After PCI
Authors: Chen Shao-Lin , Chen Wen-Ling , Ding Wang-Wang , Li Xing-Hua , Deng Hui-Min , Huang Qu-Bo
Published: June 2024

Objectives: The purpose of this research was to assess the effect of telehealth management via WeChat on improving the quality of life of patients after percutaneous coronary intervention (PCI). Methods: In this study, we retrospectively collected the clinical data of 118 patients who underwent PCI and received remote health management from our hospital via WeChat from June 2021 to September 2021 (WeChat group). The clinical data of 114 patients who underwent PCI but did not receive remote health management from our hospital from September 2020 to December 2020 were also collected (conventional group). Anxiety, depression, and quality of life scale scores were compared between the 2 groups at 6 months postdischarge. Results: Six months postdischarge, patients in the WeChat group had significantly lower Self-rating Anxiety Scale (SAS) (55.7 ± 7.2 vs 58.8 ± 6.4, P = .001) and Self-rating Depression Scale (SDS) (56.0 ± 5.9 vs 58.2 ± 6.2, P = .007) scores than did those in the conventional group. Compared to those in the conventional group, the patients in the WeChat group had significantly greater 6 months post-discharge The World Health Organization Quality of Life - BREF scores in the following domains: physical (14.3 ± 1.7 vs 13.1 ± 1.7, P < .001 psychological (15.2 ± 1.3 vs 13.5 ± 1.5, P < .001 social relationship (12.9 ± 1.7 vs 12.3 ± 1.8, P = .01) and environmental (12.7 ± 2.0 vs 12.0 ± 1.9, P = .006). Conclusion: The use of WeChat to carry out remote health management for patients who underwent PCI can be an effective way to provide high-quality hospital medical services to patients’ families and can effectively alleviate patients’ anxiety and depression and enhance their quality of life.
Mandibular Contouring in Subjects With Class II or Class III Dentofacial Deformities and Treatment Needs
Authors: Ravelo Victor , Parra Marcelo , Muñoz Gonzalo , Otero J. J. , Olate Sergio
Published: July 2024

Facial contouring relates to hard and soft structures that make up the face. Skeletal class II and III subjects present bone structure and position changes, significantly impacting the soft tissues. This study aims to analyze the morphology of the mandible at mandibular ramus and angle level in subjects with skeletal facial deformity class II and III who are candidates for orthognathic surgery and to define implications in facial contour. A cross-sectional study used cone beam computed tomography to compare the mandibular contour (mandibular angle and ramus region) in orthognathic surgery candidates. One hundred sixty orthognathic surgery candidates were analyzed, ranging in age from 18 to 58 years (31.29 ± 11.97). Regarding the skeletal class, 95 (59.37%) were skeletal class II, and 65 (40.62%) were skeletal class III. Class II subjects had a larger antegonial notch than class III subjects. Concerning the mandibular contour, class II subjects presented less vertical distance than class III subjects, but both presented similar gonial angles. Concerning the ideas to assess the need for mandibular contouring surgery, the 2 proposals to determine the need for mandibular contouring surgery in class II and III subjects present a similar distribution. The mandibular notch is an objective element and is commonly present in subjects with a class II facial pattern; this element can be used in contour analysis to define expected facial characteristics, including the patient’s facial sex, in the decision of surgical techniques for lower facial contour augmentation or reduction.
Enhancing Skin Flap Survival with Preoperative Carbon Dioxide Fractional Laser Treatment: A Novel Approach in Reconstructive Surgery
Authors: Kang Daihun
Published: July 2024

Background:

Skin flap necrosis remains a significant challenge in reconstructive surgery, predominantly due to insufficient blood supply. Traditional methods like the surgical delay procedure, while effective, are invasive and associated with considerable patient discomfort and health care costs. This study explores the efficacy of Carbon Dioxide Fractional Laser (CDFL) treatment as a novel, less invasive alternative to enhance skin flap survival.

Methods:

Twenty-nine adult male Sprague-Dawley rats were divided into 2 groups: a CDFL treatment group (n=14) and a control group (n=15). The CDFL group received laser pretreatment 1 week before flap surgery, whereas the control group underwent flap surgery without pretreatment. Flap survival was assessed 7 days postsurgery using indocyanine green fluorescence angiography. In addition, histological analysis was conducted to evaluate tissue integrity, capillary density, and VEGF expression.

Results:

The CDFL-treated flaps showed significantly increased survival areas compared with controls (P<0.01). Histological evaluation revealed enhanced capillary dilation and increased VEGF expression in the CDFL group (P<0.05). Although capillary density was higher in the CDFL group, it did not reach statistical significance (P=0.052).

Conclusion:

CDFL pretreatment significantly improves skin flap survival in rats, suggesting potential as a minimally invasive alternative to traditional surgical delay techniques. This approach could offer substantial benefits in reconstructive surgery, reducing patient morbidity and associated costs. Further studies are warranted to confirm these findings in clinical settings.
Safety of Selective Operative Drainage After Pancreatic Resection
Authors: Magnin Josephine , Jolissaint Joshua S. , Fuchs Hannah E. , Seier Kenneth , Gonen Mithat , Barekzai Ahmad , Balachandran Vinod P. , D’Angelica Michael I. , Drebin Jeffrey A. , Kingham T. Peter , Soares Kevin , Wei Alice C. , Jarnagin William R.
Published: June 2024

Objective:

To assess whether selective omission of operative drains after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is associated with adverse perioperative outcomes.

Background:

The routine use of operative drains after pancreatectomy is widely practiced; however, prospective randomized clinical trials and retrospective analyses have shown mixed results.

Methods:

Patients who underwent PD or DP between November 2009 and May 2021 were reviewed and stratified by operative drain placement. Patient demographics, morbidity, the need for additional procedures, and mortality were compared between patients who did or did not develop a clinically relevant post-operative pancreatic fistula (CR-POPF).

Results:

In total, 1,855 PD and 752 DP cases were analyzed. Among PD patients with a CR-POPF (N=259, 14%), 160 (62%) had an operative drain placed, of whom 141 (88%) required at least 1 additional procedure. Within this subgroup, grade ≥ 4 complications (7.5% vs. 11.1%, P=0.37), 90-day mortality (3.8% vs. 6.1%, P=0.54), length of stay (LOS) (median 12 vs. 13 d, P=0.19) and readmission rates (63.1% vs. 54.6%, P=0.19) were similar between drained and non-drained patients. Of note, drained PD patients without a CR-POPF had a longer hospital stay (8 vs. 7 d, respectively, P=0.004) and more thromboembolic events (2.4% vs. 1.1%, respectively, P=0.04) Among DP patients with a CR-POPF (n=129), 44 had an operative drain, with 37 (84%) requiring an additional procedure. Within this subgroup, grade ≥ 4 complications (4.6% vs. 5.9%, P>0.95), 90-day mortality (0%), LOS (median 7 d for both, P=0.88) and readmission rates (72.7% vs. 80%, P=0.38) were similar in drained and non-drained patients.

Conclusion:

This study confirms that selective omission of operative drains does not compromise perioperative outcomes, as initially reported in our prospective randomized trial.
A Prospective Comparative Analysis to Study the Impact on Voice Changes Following Endoscopic Thyroidectomy
Authors: Kumar Arun , Dhar Anita , Srivastava Anurag , Kumar Rakesh
Published: July 2024

Background:

Endoscopic approach has come up as a safe and feasible procedure for thyroidectomy with better cosmetic outcomes. However, concerns over its safety in terms of nerve injury and postoperative voice changes remain. This prospective study evaluated the role of vocal cord function assessment using laryngeal examination and voice analysis in patients who underwent endoscopic hemithyroidectomy either by the trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) or the bilateral axillobreast approach (BABA).

Methods:

Thirty-nine consecutive patients were randomly allocated to either of the 2 groups of endoscopic hemithyroidectomy; 19 in TOETVA and 20 in the BABA groups. Vocal cord function was assessed subjectively using the GRBAS scale and objectively by acoustic analysis of parameters such as jitter, shimmer, mean frequency (F0), noise-to-harmonic ratio (NHR), and maximum phonatory time (MPT) at baseline, postoperative day 10, and 3 months after surgery.

Results:

There were no significant differences in mean GRBAS scores and values of mean frequency, jitter and shimmer between the 2 groups and on postoperative day 10 and at 3 months compared with baseline. The mean NHR and MPT showed no differences between the 2 procedures. However, there was a significant decrease in their values on day 10 postsurgery, compared with baseline. These values returned to their baseline at 3 months. The other operative parameters were comparable between the 2 groups, except for the shorter mean operative time in the TOETVA group.

Conclusions:

Perioperative quantitative voice parameters were comparable with no statistically significant difference between the 2 techniques of endoscopic thyroidectomy.
Wogonin Alleviates DCD Liver Ischemia/Reperfusion Injury by Regulating ALOX15/iNOS-mediated Ferroptosis
Authors: Jia Degong , Wu Kun , Luo Jiefu , Xu Xuesong , Pan Wei , Zhao Minjie , Li Shengwei , Gong Jianping , Gong Junhua
Published: July 2024

Background.

Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now suggests that ferroptosis plays a key regulatory role in the development of IRI, so targeting ferroptosis may be an effective strategy to alleviate IRI in liver transplantation (LT).

Methods.

Using donation after circulatory death LT models in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) models in BRL-3A cells, we tested the effect of the Chinese medicine monomer wogonin on liver IRI and explored the specific mechanism.

Results.

Wogonin attenuated liver IRI and increased the survival rate of rats by inhibiting lipid peroxidation and ferroptosis. Mechanistically, arachidonic acid 15-lipoxygenase-1 (ALOX15) and inducible nitric oxide synthase (iNOS) were identified as potential targets of baicalein through bioinformatics analysis combined with in vivo and in vitro experiments. This result was further confirmed by molecular docking and cellular thermal shift assays. Finally, we silenced ALOX15 and iNOS in the OGD/R cell model and found that silencing ALOX15 and iNOS could reproduce the regulatory effect of wogonin and abrogate the regulatory effect of wogonin.

Conclusions.

In brief, this study emphasizes that wogonin exerts a protective effect in liver IRI through the regulation of ALOX15- and iNOS-mediated ferroptosis. ALOX15 and iNOS are potential targets for intervention in IRI induced by LT, and wogonin is a drug candidate for LT patients.
Comparative analysis of third-generation antipsychotics in first-episode schizophrenia: efficacy, safety, and cognitive impacts. A narrative review
Authors: Ricci Valerio , Sarni Alessandro , Martinotti Giovanni , Maina Giuseppe
Published: June 2024

Background and objectives

Schizophrenia is a chronic, complex mental health disorder requiring effective management to mitigate its broad personal and societal impacts. This narrative review assesses the efficacy, effectiveness, and side effects of third-generation antipsychotics (TGAs) like aripiprazole, brexpiprazole, and cariprazine, focusing on their use in first-episode schizophrenia. These drugs aim to reduce side effects typical of earlier antipsychotics while more effectively addressing positive and cognitive symptoms.

Methods

Our extensive literature review, using PubMed and Scopus, includes randomized controlled trials and observational studies, showing TGAs may match older antipsychotics in efficacy with fewer side effects, notably in reducing extrapyramidal symptoms and enhancing cognitive outcomes.

Results

Aripiprazole appears effective in both acute and maintenance phases of schizophrenia, while brexpiprazole and cariprazine show potential in managing negative symptoms and improving social functioning, essential for patient recovery.

Conclusions

This review emphasizes the need for personalized treatment and further research to fully determine the long-term benefits and safety of TGAs. These findings can inform clinical decisions and underline the ongoing need for innovation in schizophrenia pharmacotherapy.
Multiple novel caliciviruses identified from stoats (Mustela erminea) in the United Kingdom
Authors: Hinds Joseph , Apaa Ternenge , Parry Rhys H. , Withers Amy J. , MacKenzie Laura , Staley Ceri , Morrison Joshua , Bennett Malcolm , Bremner-Harrison Samantha , Chadwick Elizabeth A. , Hailer Frank , Harrison Stephen W.R. , Lambin Xavier , Loose Matthew , Mathews Fiona , Tarlinton Rachael , Blanchard Adam
Published: June 2024

The Caliciviridae family, comprising positive-sense RNA viruses, is characterised by its non-enveloped, small virions, broad host range, and notable tendency for host switching. These viruses are primarily associated with gastroenteric disease, though they can lead to haemorrhagic or respiratory infections. Our study employed a metagenomics analysis of faecal samples from stoats (Mustela erminea), identifying two novel calicivirus species, named stoat vesivirus and stoat valovirus. Stoat vesivirus was identified in three samples (ST008, ST006, ST004), exhibiting a genome wide nucleotide identity of approximately 92%. The complete coding sequences of these samples were 8471 (ST004) and 8322 (ST006) nucleotides in length, respectively. Each comprised three open reading frames (ORF), closely resembling the Vesivirus mink calicivirus (China/2/2016), with 70-72% similarity in ORF1, 61-62% in ORF2 and 71% in ORF3. Phylogenetic analysis robustly supported stoat vesivirus as belonging within the Vesivirus genus. The second calivicirus (stoat valovirus), detected solely in sample ST008, was 6527 nucleotides in length and with complete coding sequences present. It shared highest similarity with St-Valerien swine virus and marmot norovirus HT16, showing 39.5% and 38.8% protein identity with ORF1 and 43.3% and 42.9% for VP1. Stoat valovirus is borderline for meeting the ICTV criteria for a new genus, demonstrating 60% divergence in ORF1 compared to the other valovirus’, however it clusters basally within the Valovirus genus, supporting leaving it included in this genus.
ComBatLS: A location- and scale-preserving method for multi-site image harmonization
Authors: Gardner Margaret , Shinohara Russell T. , Bethlehem Richard A.I. , Romero-Garcia Rafael , Warrier Varun , Dorfschmidt Lena ,   Lifespan Brain Chart Consortium, Shanmugan Sheila , Thompson Paul , Seidlitz Jakob , Alexander-Bloch Aaron F. , Chen Andrew A.
Published: June 2024

Recent work has leveraged massive datasets and advanced harmonization methods to construct normative models of neuroanatomical features and benchmark individuals’ morphology. However, current harmonization tools do not preserve the effects of biological covariates including sex and age on features’ variances; this failure may induce error in normative scores, particularly when such factors are distributed unequally across sites. Here, we introduce a new extension of the popular ComBat harmonization method, ComBatLS, that preserves biological variance in features’ locations and scales. We use UK Biobank data to show that ComBatLS robustly replicates individuals’ normative scores better than other ComBat methods when subjects are assigned to sex-imbalanced synthetic “sites”. Additionally, we demonstrate that ComBatLS significantly reduces sex biases in normative scores compared to traditional methods. Finally, we show that ComBatLS successfully harmonizes consortium data collected across over 50 studies. R implementation of ComBatLS is available athttps://github.com/andy1764/ComBatFamily.
Evaluate the efficiency of Mr BMT in macrophage replacement of peripheral organs
Authors: Du Jinjin , Yang Baozhi , He Yang , Rao Yanxia
Published: June 2024

The successful replacement of endogenous tissue-resident macrophages with healthy bone marrow-derived cells through transplantation presents a promising therapeutic approach for treating disease associated with macrophage dysfunction. Our previous development of the novel microglia replacement by bone marrow transplantation (Mr BMT) method achieved high engraftment efficiency in the central nervous system (CNS), overcoming the limitation of traditional bone marrow transplantation (tBMT). In this study, we aimed to investigate the potential impacts of Mr BMT approach on peripheral organs. The Mr BMT approach involves depleting resident microglia through colony stimulating factor-1 receptor (CSF-1R) inhibition, so we first evaluated the survival of peripheral macrophages after CSF-1R inhibition. We observed that the CSF-1R antagonist, PLX5622, exerted significant elimination of peripheral tissue macrophages, albeit with lower efficiency than in the CNS. Furthermore, we discovered that Mr BMT achieved replacement efficiencies comparable to tBMT in peripheral tissues such as the liver, kidney, lung, and spleen. Our findings suggested Mr BMT is a highly efficient strategy for allogeneic macrophage replacement in both the CNS and peripheral organs, and it could have potential clinical applications.
Regulator of G Protein Signaling 14 protein expression profile in the adult mouse brain
Authors: Bramlett Sara N. , Fitzmaurice Shana M. , Harbin Nicholas H. , Yan Wuji , Bandlamudi Charan , Van Doorn G. Emme , Smith Yoland , Hepler John R.
Published: June 2024

Regulator of G protein signaling 14 (RGS14) is a multifunctional signaling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with adult rhesus macaque brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra, and amygdala in the adult rhesus monkey brain. In the mouse brain, we also have observed RGS14 protein in discrete limbic regions linked to reward behavior and addiction, including the central amygdala and the nucleus accumbens, but a comprehensive mapping of RGS14 protein expression in the adult mouse brain is lacking. Here, we report that RGS14 is more broadly expressed in mouse brain than previously known. Intense RGS14 staining is observed in specific neuron populations of the hippocampal formation, amygdala, septum, bed nucleus of stria terminalis and ventral striatum/nucleus accumbens. RGS14 is also observed in axon fiber tracts including the dorsal fornix, fimbria, stria terminalis, and the ventrohippocampal commissure. Moderate RGS14 staining is observed in various other adjacent regions not previously reported. These findings show that RGS14 is expressed in brain regions that govern aspects of core cognitive functions such as sensory perception, emotion, memory, motivation, and execution of actions, and suggests that RGS14 may serve to suppress plasticity and filter inputs in these brain regions to set the overall tone on experience-to-action processes.
An improved tetracycline-inducible expression system for fission yeast
Authors: Lyu Xiao-Hui , Yang Yu-Sheng , Pan Zhao-Qian , Ning Shao-Kai , Suo Fang , Du Li-Lin
Published: June 2024

The ability to manipulate gene expression is valuable for elucidating gene function. In the fission yeastSchizosaccharomyces pombe, the most widely used regulatable expression system is thenmt1promoter and its two attenuated variants. However, these promoters have limitations, including a long lag, incompatibility with rich media, and unsuitability for non-dividing cells. Here, we present a tetracycline-inducible system free of these shortcomings. Our system features theenotetSpromoter, which achieves a similar induced level and a higher induction ratio compared to thenmt1promoter, without exhibiting a lag. Additionally, our system includes four weakenedenotetSvariants, offering an expression range similar to thenmt1series promoters but with more intermediate levels. To enhance usability, each promoter is combined with a Tet-repressor-expressing cassette in an integration plasmid. Importantly, our system can be used in non-dividing cells, enabling the development of a synchronous meiosis induction method with high spore viability. Moreover, our system allows for the shutdown of gene expression and the generation of conditional loss-of-function mutants. This system provides a versatile and powerful tool for manipulating gene expression in fission yeast.

Summary statement

A new inducible expression system for fission yeast enhances control, offers compatibility with non-dividing cells, and enables synchronous meiosis induction and conditional loss-of-function analysis.
The Bayesian Phylogenetic Bootstrap, Application to Short Trees and Branches
Authors: Lemoine Frederic , Gascuel Olivier
Published: June 2024

Felsenstein's bootstrap is the most commonly used method to measure branch support in phylogenetics. Current sequencing technologies can result in massive sampling of taxa (e.g. SARS-CoV-2). In this case, the sequences are very similar, the trees are short, and the branches correspond to a small number of mutations (possibly 0). Nevertheless, these trees contain a strong signal, with unresolved parts but a low rate of false branches. With such data, Felsenstein's bootstrap is not satisfactory. Due to the frequentist nature of bootstrap sampling, the expected support of a branch corresponding to a single mutation is ~63%, even though it is highly likely to be correct. Here we propose a Bayesian version of the phylogenetic bootstrap in which sites are assigned uninformative prior probabilities. The branch support can then be interpreted as a posterior probability. We do not view the alignment as a small subsample of a large sample of sites, but rather as containing all available information (e.g., as with complete viral genomes, which are becoming routine). We give formulas for expected supports under the assumption of perfect phylogeny, in both the frequentist and Bayesian frameworks, where a branch corresponding to a single mutation now has an expected support of ~90%. Simulations show that these theoretical results are robust to realistic data. Analyses on low-homoplasy viral and non-viral datasets show that Bayesian bootstrap support is easier to interpret, with high supports for branches very likely to be correct. As homoplasy increases, the two supports become closer and strongly correlated.
100 years domestication of penaeid shrimp and meta-analysis of breeding traits
Authors: Ren Shengjie , Yáñez José M. , Perez-Enriquez Ricardo , Rye Morten , Houston Ross D. , Hurwood David A. , Gonzalez-Galaviz Jose R. , Salazar Marcela , Jerry Dean R.
Published: June 2024

Penaeid shrimp farming plays a pivotal role in ensuring future food security and promoting economic sustainability. Compared to the extensive long history of domestication observed in terrestrial agriculture species, the domestication and selective breeding of penaeids are relatively recent endeavors. Selective breeding aimed at improving production traits holds significant promise for enhancing efficiency and reducing the environmental impact of shrimp farming, thereby contributing to its long-term sustainability. Assessing genotype-by-environment (G-by-E) interactions is essential in breeding programs to ensure that improved penaeid shrimp strains perform consistently across different production environments, with genomic selection proving more effective than sib-testing alone in mitigating environmental sensitivity. Genome editing tools like CRISPR/Cas9 offer significant potential to accelerate genetic gains in penaeid shrimp by enabling rapid introduction of desired genetic changes, with recent advancements showing promising results in achieving high transfection efficiency in shrimp embryos. Additionally, artificial intelligence and machine learning are being leveraged to streamline phenotyping and enhance decision-making in shrimp breeding and farming, improving efficiency and accuracy in managing traits and predicting disease outbreaks. Herein, we provide an overview and update on the domestication of penaeid shrimp, including the current status of domestication for principal farmed species, key milestones in domestication history, targeted breeding traits in selective breeding programs, the advantages of integrating genomeic selection for enhancing production traits, and future directions for selective breeding of penaeid shrimp.
A Computational Approach to Interpreting the Embedding Space of Dimension Reduction
Authors: Zhang Bingyuan , Uno Kohei , Kodama Hayata , Himori Koichi , Matsui Yusuke
Published: June 2024

Nonlinear dimension reduction methods are widely applied in studies analyzing gene and protein expression, by revealing patterns of discrete groups and continuous orders in high-dimensional data. However, the tools are limited to understanding the obtained embedding structures of biological mechanisms, hindering the full exploitation of data. Here, we propose a novel framework to interpret embedding systematically by identifying and mapping associated biological functions. The method performs statistical tests and visualizes significantly enriched functions essential for the organization of the embedding structure, by applying it to the embedding results of two datasets: the Genotype Tissue Expression dataset and aCaenorhabditis elegansembryogenesis dataset, one capturing distinct cluster structures and the other capturing continuous developmental trajectories. We identified the associated functions for interpreting the two embeddings and confirmed it as a useful explainable AI tool in exploratory data analysis by providing annotations to the embedding space.
The development of ecological systems along paths of least resistance
Authors: Deng Jie , Cordero Otto X. , Fukami Tadashi , Levin Simon A. , Pringle Robert M. , Solé Ricard , Saavedra Serguei
Published: June 2024

A long-standing question in biology is whether there are common principles that characterize the development of ecological systems (the appearance of a group of taxa), regardless of organismal diversity and environmental context. Classic ecological theory holds that these systems develop following a sequenced orderly process that generally proceeds from fast-growing to slow-growing taxa and depends on life-history trade-offs. However, it is also possible that this developmental order is simply the path with the least environmental resistance for survival of the component species and hence favored by probability alone. Here, we use theory and data to show that the order from fast-to slow-growing taxa is the most likely developmental path for diverse systems when local taxon interactions self-organize to minimize environmental resistance. First, we demonstrate theoretically that a sequenced development is more likely than a simultaneous one, at least until the number of iterations becomes so large as to be ecologically implausible. We then show that greater diversity of taxa and life histories improves the likelihood of a sequenced order from fast-to slow-growing taxa. Using data from bacterial and metazoan systems, we present empirical evidence that the developmental order of ecological systems moves along the paths of least environmental resistance. The capacity of simple principles to explain the trend in the developmental order of diverse ecological systems paves the way to an enhanced understanding of the collective features characterizing the diversity of life.
β-defensin gene copy number variation in cattle
Authors: Sidekli Ozge , Oketch John , Fair Sean , Meade Kieran G. , Hollox Edward J.
Published: June 2024

β-defensins are peptides with antimicrobial roles, characterized by a conserved tertiary structure. Beyond antimicrobial functions, they exhibit diverse roles in both the immune response and fertility, including involvement in sperm maturation and function. Copy number variation (CNV) of β-defensin genes is extensive across mammals, including cattle, with possible implications for reproductive traits and disease resistance. In this study, we comprehensively catalogue 55 β-defensin genes in cattle. By constructing a phylogenetic tree to identify human orthologues and lineage-specific expansions, we identify 1:1 human orthologues for 35 bovine β-defensins. We also discover extensive β-defensin gene CNV across breeds, withDEFB103in particular showing extensive multiallelic CNV. By comparing β-defensin expression levels in testis from calves and adult bulls, we find that 14 β-defensins, includingDEFB103, increase in expression during sexual maturation. Analysis of β-defensin gene expression levels in the caput of adult bull epididymis, and β-defensin gene copy number, in 94 matched samples shows expression level of four β-defensins are correlated with genomic copy number, includingDEFB103. We therefore demonstrate extensive copy number variation in bovine β-defensin genes, in particularDEFB103, with potential functional consequences for fertility.
High-resolution chromosome-level genome provides molecular insights into adaptive evolution in crabs
Authors: Zhang Yin , Yuan Ye , Zhang Mengqian , Yu Xiaoyan , Qiu Bixun , Wu Fangchun , Tocher Douglas R. , Zhang Jiajia , Ye Shaopan , Cui Wenxiao , Leung Jonathan Y. S. , Ikhwanuddin Mhd , Waqas Waqas , Dildar Tariq , Ma Hongyu
Published: June 2024

Crabs thrive in diverse ecosystems, from coral reefs to hydrothermal vents and terrestrial habitats. Here, we report a comprehensive genomic analysis of the mud crab using ultralong sequencing technologies, achieving a high-quality chromosome-level assembly. The refined 1.21 Gb genome, with an impressive contig N50 of 11.45 Mb, offers a valuable genomic resource. Gene family analysis shows expansion in development-related pathways and contraction in metabolic pathways, indicating niche adaptations. Notably, Investigation into Hox gene regulation sheds light on their role in pleopod development, with theAbd-Agene identified as a linchpin. Posttranscriptional regulation involving novel-miR1317 negatively regulatesAbd-Alevels. Furthermore, thefrugene’s potential role in ovarian development and the identification of novel-miRNA-35 as a regulator ofSpfru2add complexity to gene regulatory networks. Comparative functional analysis across Decapoda species reveals neofunctionalization of theelovl6gene in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA), suggesting its importance in environmental adaptation. These findings contribute significantly to our understanding of crab adaptability and evolutionary dynamics, offering a robust foundation for future investigations.