bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between gut microbiota, plasma metabolites, and ovarian cancer: A Mendelian randomization study
Authors: Wang Yu , Gao Shanxiang , Liu Yangyu , Li Yongai , Yao Hui , Han Yan , Liu Xinyue
Published: November 2024

Numerous studies have demonstrated a correlation between alterations in gut microbiota (GM) and levels of body metabolites in ovarian cancer (OC). However, the specific causal relationships underlying these associations remain unclear. This study utilized summary statistics of GM from the MiBioGen consortium, along with an unprecedented dataset comprising 1091 blood metabolites and 309 metabolite ratios from the UK Biobank, in conjunction with OC data from the FinnGen Consortium R9 release. We conducted bidirectional Mendelian randomization (MR) analyses to investigate the causal relationships between GM and OC. Additionally, a two-step MR approach was employed to identify potential mediating metabolites. Our analysis revealed significant associations between 6 specific microbiota taxa and OC. Furthermore, we identified several plasma metabolites that act as mediators of the association between GM and OC. In the two-step MR analysis, we observed a negative correlation between 4-methoxyphenol sulfate and pregnenetriol disulfate levels with OC. The genus Lachnospiraceae UCG008 potentially increases the risk of OC by decreasing 4-methoxyphenol sulfate levels, while the genus Howardella may elevate the risk of OC by reducing pregnenetriol disulfate levels, with mediation proportions of 22.35% and 4.23%, respectively. Additionally, levels of dilinoleoyl-GPE (18:2/18:2) and N-acetylkynurenine (2) were positively correlated with OC. The inhibitory effect of the genus Ruminococcus 1 on OC may be mediated through 1,2-dilinoleoyl-GPE (18:2/18:2) and N-acetylkynurenine (2), with mediation proportions of 10.15% and 11.32%, respectively. Our findings highlight the complex relationship among GM, plasma metabolites, and OC. The identified associations and mediation effects offer valuable insights into potential therapeutic approaches targeting GM for the management of OC.
Factors associated with subtherapeutic levels of valproic acid in hospitalized patients with epilepsy: A retrospective cohort study
Authors: Boonlue Tuanthon , Sitsuer Papitchaya , Phosri Wasinee , Jinatongthai Warisara
Published: November 2024

Valproic acid (VPA) is a commonly used anti-seizure medication, owing to its efficacy and cost-effectiveness. However, maintaining appropriate serum levels is crucial due to the narrow therapeutic window, as subtherapeutic levels can lead to treatment failure or adverse outcomes. This study aimed to identify the factors associated with subtherapeutic serum levels of valproic acid in patients undergoing treatment. This retrospective cohort study was performed at a tertiary care hospital and involved inpatients aged ≥ 18 years who were receiving valproic acid for epilepsy treatment. Data were obtained through chart reviews and a Therapeutic Drug Monitoring database. Subtherapeutic VPA levels were defined as < 50 mg/L. Logistic regression was used to identify risk factors for subtherapeutic levels. Of the 152 patients, 96 (63.2%) had subtherapeutic VPA levels (<50 mg/L). Males were more likely than females to have subtherapeutic levels (OR 2.45, 95% CI: 1.15–5.22; P = .02). Previous use of phenytoin significantly increased the risk of subtherapeutic VPA levels (OR 2.58, 95% CI: 1.16–5.71; P = .02). VPA administration by syrup and doses below 15 mg/kg/day were associated with subtherapeutic levels (OR 3.28 and 2.34, respectively). Additionally, co-medications, such as topiramate and meropenem, also increased this risk (OR 5.09 and 4.64, respectively). This study identified several factors significantly associated with subtherapeutic levels of valproic acid, including males, prior phenytoin use, co-medications, such as topiramate and meropenem, and lower VPA dosages. These findings underscore the importance of careful monitoring and individualized treatment plans to maintain therapeutic VPA levels in clinical practice. Further research is needed to explore the clinical implications and to develop strategies to minimize the risk of subtherapeutic levels in patients receiving VPA.
Effect of mental state on sleep quality in patients receiving maintenance hemodialysis: A multiple mediation model of hope and family function
Authors: Li Qiang , Xia Fuhai , Wang Guoqing , Chen Rui , Chen Guangsen
Published: November 2024

The objective of this study was to investigate the current situation of sleep quality in patients receiving maintenance hemodialysis (MHD), and whether hope and family function play a mediating role between negative emotions and sleep quality. The Athens Insomnia Scale, Hospital Anxiety and Depression Scale, Herth Hope Index and Family Adaptation, Partnership, Growth, Affection and Resolve (APGAR) Index were used to investigate 227 MHD patients. The correlations among study variables were analyzed by Pearson correlation analysis. Structural equation model was used to construct and evaluate the mediation model. The sleep quality score of 227 patients receiving MHD was (7.57 ± 4.74), anxiety score was (4.36 ± 4.02), depression score was (5.91 ± 4.37), hope score was (34.64 ± 7.21), family function score was (6.21 ± 2.90). The negative emotions can directly predict sleep quality (β = 0.17, P = .046), positively predict sleep quality through hope (β = 0.12, P = .017), positively predict sleep quality through family function (β = 0.20, P < .001), and positively predict sleep quality through the chain mediating of hope and family function (β = 0.10, P < .001). The total effect size was 71.19%. It is concluded that negative emotions had a direct impact on the sleep quality of patients receiving MHD, and that improving the levels of family function and hope can help them sleep better.
A descriptive analysis of 21 patients with pulmonary amyloidosis: An observational study
Authors: Demirkol Baris , Satici Celal , Eren Ramazan , Ugur Chousein Efsun Gonca , Senkal Naci , Turan Demet , Urer Halide Nur , Cetinkaya Erdogan
Published: November 2024

Pulmonary amyloidosis is an extremely rare disease, often detected incidentally because of its asymptomatic nature and potential to result in fatal outcomes. In this study, we aimed to present the clinical and radiological features of patients diagnosed with pulmonary amyloidosis by biopsy. This descriptive study included 21 patients with pathologically diagnosed pulmonary amyloidosis. Pulmonary amyloidosis was classified as diffuse alveolar-septal amyloidosis (DASA), cystic amyloidosis (CPA), tracheobronchial amyloidosis (TBA), nodular amyloidosis (NPA), and extraparenchymal pulmonary amyloidosis (pleural and mediastinal lymph node). Clinical, bronchoscopic, and radiological specific characteristics were presented in detail to be used for differential diagnosis. The median age of the patients was 63 (40–83) years, and 14 (66.7%) were male. Twenty patients (95.2%) presented with at least 1 comorbidity. All patients diagnosed with tracheobronchial amyloidosis were symptomatic at presentation, whereas those diagnosed with NPA/extraparenchymal amyloidosis were often asymptomatic. The patients included 1 case of DASA, 1 case of CPA, 10 cases of NPA, 6 cases of TBA, and 3 cases of extraparenchymal amyloidosis involving the mediastinal lymph node and pleura. Sixteen patients (76.2%) were classified as localized amyloidosis, while 5 patients (23.8%) were classified as systemic amyloidosis following the diagnosis of multiple myeloma, monoclonal gammopathy of undetermined significance, systemic lupus erythematosus, Sjogren’s syndrome, and B-cell lymphoma. Bronchoscopic biopsies were sufficient for diagnosis, and notably, even transbronchial needle aspiration could be a useful diagnostic method. During the follow-up, we observed that the disease remained stable without progression. However, it is important to note that patients with concurrent malignancies experience fatal outcomes. In conclusion, it is crucial to distinguish pulmonary amyloidosis from other pulmonary diseases such as malignancies, infectious diseases, and interstitial lung diseases, which may have similar clinical and radiological findings. Bronchoscopic diagnostic methods are usually sufficient for the diagnosis. Although patients with pulmonary involvement mostly remain stable during long-term follow-up without progression, it is important to consider the risk of malignancy.
Effect of Donor/Recipient ABO Mismatch on Outcome of Allogenic Hematopoietic Stem Cell Transplantation in Children: Single-center Study
Authors: El-Kaffas Asmaa Abdel-Raof , El-Barky Amany Mahmoud , Elhawary Eslam Elsayed
Published: November 2024

ABO blood group mismatch between donor and recipient is thought to be associated with several immunopharmacological complications but is not considered a major contraindication to allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of such a mismatch on overall survival, transplant-related mortality, graft-versus-host disease, and time to neutrophil and platelet engraftment seems to be conflicting. This retrospective cohort was carried out on children and adolescents who underwent allogenic HSCT between January 2016 and January 2023. ABO compatibility state was assessed and grouped into compatible, minor, major, and bidirectional incompatible groups. The effect of ABO compatibility on various transplantation outcomes was assessed. Forty-three children (25 males and 18 females) with different diagnoses were included. More than half of the patients had no ABO mismatch. Major ABO mismatch was found to be associated with a higher incidence of acute graft-versus-host-disease (aGVHD), whereas near significantly higher mortality was observed in the minor mismatch group. Otherwise, no association was found between ABO mismatch and platelet or neutrophil engraftment. ABO mismatch does not affect the overall survival or the posttransplant engraftment of patients undergoing allogeneic HSCT. aGVHD was observed to be the only factor affected by ABO compatibility.
Advancements in breast cancer management: a comprehensive review of ribociclib combined with endocrine therapy
Authors: Qureshi Zaheer , Altaf Faryal , Safi Adnan , Khanzada Mikail , Ghazanfar Ali , Shah Shivendra
Published: November 2024

Background:

In this review, the complicated landscape of breast cancer management is explored with a focus on the promising synergies between ribociclib and endocrine therapy. Ribociclib mainly acts as a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, which disrupts cell cycle progression necessary for tumor growth. This, in combination with endocrine therapy, aims to produce hormone receptor-positive breast cancers, which is a very relevant subtype with challenging therapeutics.

Methods:

A comprehensive review was conducted using multiple databases, PubMed, Embase, Scopus, Cochrane Library, and Web of Science, covering the period from January 1990 to May 2024.

Results:

Pharmacokinetic studies underscore the efficacy and tolerability of ribociclib, thus providing vital information for dose adjustments, particularly among patients with renal and hepatic impairments. Ribociclib’s value in extending progression-free survival and improving overall survival has been shown by clinical trials such as the MONALEESA series. Quality of life considerations and patient-reported outcomes from these trials indicate that ribociclib has a broader effect on the well-being of the patients. However, despite the success experienced by this drug in clinical practice, it still has some side effects, including hematologic toxicity, hepatotoxicity, and thromboembolism associated with it. Ribociclib resistance mechanisms are multifaceted mixtures comprising genetic variations or mutations, compensatory signaling pathways, and epigenomic changes. While overcoming resistance remains challenging, ongoing research seeks to reconcile.

Conclusion:

Ribociclib combined with endocrine therapy represents a significant advancement in breast cancer treatment, albeit with challenges that necessitate ongoing research and holistic patient care approaches.
Navigating Voluntarily Stopping Eating and Drinking in Hospice Settings
Authors: Day Jamie M. , Woodley Lisa , Ivancic Margaret
Published: November 2024

This article explores current global research on voluntarily stopping eating and drinking (VSED) and presents a detailed, deidentified case study of a patient who elected VSED in a hospice setting in the Southeastern United States. It highlights the collaborative efforts of health care professionals in effectively supporting the patient and family, sharing multiple perspectives from various health care team members who cared for the patient and family. It offers evidence-based recommendations to guide health care teams through the ethical, medical, and emotional challenges of VSED, ensuring compassionate and competent care. The article emphasizes the importance of structured protocols and empathetic care in hospice settings, advocating for the education and preparation of health care teams and families to address the complex challenges associated with VSED. By promoting open communication, interdisciplinary collaboration, and comprehensive support, hospices can respect the autonomy of patients and families choosing VSED, ensuring a compassionate and dignified end-of-life experience.
Exploring Protein Dietary Guidance Statements
Authors: Hicks-Roof Kristen K.
Published: November 2024

Consumers may benefit from quick signals on or nearby food product to nudge them toward choosing healthier diets, such as Dietary Guidance Statements (DGSs) from the US Food and Drug Administration. It is unclear how DGSs on foods, including animal or plant proteins, impact purchase motivation, believability, or willingness to pay more. Six DGS claims were tested across 5 protein types (pork tenderloin, beef top sirloin fillet, chicken breast, turkey breast, and plant-based meat) using an online prediction market test survey format among 1002 nationally representative US-based household primary grocery shoppers aged 18 to 64 years. The most motivating and believable DGS across protein types was the Dietary Guidelines DGS: The Dietary Guidelines for Americans recommends eating 5½ oz of protein food per day as part of a nutritious dietary pattern.  is a lean meat that provides 3 oz of protein food per serving (based on a 2000-calorie diet). More than one-third felt that this Dietary Guidelines DGS was the most motivating and believable because it was informative; imparted feelings of the protein type being healthy; contained statistics, facts, or numbers; and mentioned the US Dietary Guidelines for Americans. More than 50% of participants were willing to pay at least 5% or more for the protein type specified in the Dietary Guidelines DGS across all protein types. Uniform adoption of DGSs across protein food groups allows for equal representation of how a variety of proteins can contribute to a nutritious dietary pattern.
Advances in neoadjuvant therapy for resectable intrahepatic cholangiocarcinoma: An invited commentary
Authors: Han Ruyu , Song Peipei , Tang Wei , Song Tianqiang , Chen Lu
Published: November 2024

Intrahepatic cholangiocarcinoma (ICC) poses a significant threat to human health owing to its high malignancy rate and poor prognosis. Surgery is the most effective treatment option for ICC. However, the prognosis remains unfavorable even after surgical resection. Therefore, neoadjuvant therapy has emerged as a potential treatment option for patients with ICC. Neoadjuvant therapy can improve patient prognosis by reducing the tumor size and eliminating tiny lesions that are not visible to the naked eye. Nevertheless, specific treatment options for neoadjuvant therapy are unavailable. This review summarizes the studies on neoadjuvant therapy for ICC in the last decade, including chemotherapy, radiotherapy, interventional therapy, targeted therapy, and immunotherapy, with the aim of providing suggestions for the selection of clinical treatment options for patients with ICC. Current reports suggest that chemotherapy is the most effective neoadjuvant treatment option. However, radiotherapy and interventional therapies require further investigation to obtain conclusive recommendations. Although targeted therapies and immunotherapies have been studied less extensively, several ongoing clinical trials are investigating these promising approaches.
Diagnosis and Risk Stratification of Ovarian Mucinous Neoplasms: Pattern of Invasion, Immunohistochemistry, and Molecular Diagnostics
Authors: Köbel Martin , Parra-Herran Carlos , Gorringe Kylie
Published: November 2024

Ovarian mucinous tumors are subclassified in multiple categories. Recent studies have highlighted issues in interobserver reproducibility. This review will focus on some new developments including criteria and ancillary tests that may help to improve interobserver reproducibility at clinically important thresholds. These issues include proposals for a separate terminology of teratoma-associated ovarian mucinous neoplasms, the role of TP53 immunohistochemistry in distinction of crowded mucinous borderline tumors and expansile mucinous carcinomas as well as the assignment of the infiltrative pattern of invasion, which recently has been validated as important prognostic factor even in low stage mucinous ovarian carcinoma.
Vascularized Bone Reconstruction for Recalcitrant Clavicular Nonunion
Authors: Chiang Jenny , Karunaratne Yasiru Gehan , Romeo Pascalino , Sim Ivanna Ting Mei , Graham David , Sivakumar Brahman
Published: November 2024

Purpose

Clavicular nonunion is an uncommon complication with a significant impact on quality of life and can be difficult to manage. In recalcitrant cases, or situations unfavorable for take of nonvascularized grafts, vascularized osseous reconstruction may be utilized. Several donor sites for such flaps have been described, with each associated with unique benefits and drawbacks.

Methods

A systematic review utilizing MEDLINE and Embase databases was performed for cases of vascularized bone reconstruction for clavicle nonunion.

Results

Twenty-six papers met inclusion, comprising 67 patients. Mean age was 43.1 years, across 32 male and 35 female patients. Mean period of nonunion was 43.2 months in the fibular group, 42.0 months in the medial femoral condyle (MFC), and 12 months in the rib flap group. Patients had undergone a mean of 2.67 prior operations at the time of vascularized osseous flap; a proportion of patients had undergone prior locoregional radiotherapy (9/26) or been complicated by infection (12/22). Radiological union was achieved in 95.2% (20/21) of fibular flaps, 95.6% (25/27) of MFC flaps, and 66.7% (2/3) of rib flaps. Mean time to union was 10.6 months for the fibular group, 7.8 months for the MFCs, and 4.0 months for the rib flaps. Complications occurred in 55.6% (20/36) of patients having fibular flaps, 26.1% (6/23) of MFC flaps, and 50% (2/4) of rib flaps.

Conclusions

All osseous flaps yielded similar and consistent rates of union when used to reconstruct defects of the clavicle. Higher complication rates, particularly donor site morbidity, were noted with fibula and rib flaps when compared to the MFC.
Facial Artery Branch Thrombolysis for Nasal Vascular Embolism Induced by Hyaluronic Acid Injection
Authors: Yang Hong , Zheng Yan , Li Dan , Li Tian-zhu , Zhao Jian-hui , Shu Kai-yi , Cao Li-li , Guo Tian-lin , Ye Fei-lun
Published: November 2024

Background

Vascular embolism is a severe complication following hyaluronic acid (HA) filler injections, with hyaluronidase injection being the most effective treatment. The nasal region, including the nose and nasolabial fold, is the most common site of vascular embolism after facial HA injections. Currently, there is insufficient clinical evidence regarding the benefits of facial artery thrombolysis.

Objectives

This article aimed to evaluate the efficacy of hyaluronidase injection via the facial artery as an emergency treatment for vascular embolism induced by facial aesthetic HA fillers.

Methods

We reviewed 14 patients who experienced nasal vascular embolism following facial HA filler injections. All 14 patients underwent percutaneous facial artery thrombolysis with a combination of hyaluronidase and urokinase administered intravascularly. For patients with longer occlusion duration and severe necrosis, femoral artery interventional thrombolysis was performed, with local injection of platelet-rich plasma to promote recovery. Follow-up ranged from 1 month to 1 year.

Results

Following facial artery hyaluronidase injection, all cases showed improvement in nasal skin lesions. Twelve patients fully recovered, while 2 patients were left with minor superficial scars and defects in the nasal wings.

Conclusions

Early thrombolysis postnasal embolism is crucial, and percutaneous facial artery puncture is an effective emergency treatment. Arterial intervention targeting the facial artery in the nasolabial fold may offer more precise thrombolysis. The combined use of hyaluronidase and urokinase is both safe and effective.
Micro/Nanobubble-Assisted Lipotransfer
Authors: Halaseh Faris F. , Sherafat Arya , Zaki Daniel P. , Alaniz Leonardo , Rahimian Helia , Tang Jordan , Arora Jagmeet , Sayadi Lohrasb R. , Evans Gregory R.D. , Ziegler Mary , Widgerow Alan D.
Published: November 2024

Objective

Retention rates of lipotransfer remain variable, with the underlying cause associated with tissue oxygenation and blood supply barriers. One promising new method of improving tissue oxygenation is micro/nanobubbles (MNBs), which are small gas bubbles (<100 μm) generated within a saline solution. MNBs are stable and carry a significant amount of oxygen, and because of their negatively charged surface characteristics, they are an ideal oxygen-delivery solution. Thus, we hypothesize that washing/oxygenating lipoaspirate tissue prior to transplantation in a micro/nanobubble saline solution will improve graft survival and quality compared to a saline control.

Methods

Human lipoaspirate samples obtained from healthy donors were washed with an oxygenated MNB or saline wash. These samples were then injected into the dorsum of sixteen 6-week-old male BALB/c mice, where each mouse received one saline and one MNB-washed graft. At 2-, 4-, 8-, and 12-week time points, the explants were harvested and weighed, and gas pycnometry was performed to assess graft volume. The tissues were also subjected to hematoxylin and eosin (HE) staining and immunohistochemistry to detect perilipin and blood vessels (CD31). These stains, as well as adipocyte count and area quantifications, were analyzed using ImageJ.

Results

HE staining revealed that the control group demonstrated notable adipocyte hypertrophy, while MNB-washed samples had evident adipocyte hyperplasia. This observation was confirmed by an analysis of variance (ANOVA), which showed that the control group had a larger average graft mass and volume (P < 0.01). MNB-washed grafts also exhibited significantly greater adipocyte counts and smaller adipocytes (P < 0.001). Perilipin staining was also greater in the MNB group at the 2- and 4-week time point indicating improved de novo adipogenesis following implantation. Lastly, CD31 staining revealed a significantly greater core vessel density and angiogenesis at the 4-week and 12-week time points (P < 0.01).

Conclusions

Our study demonstrates that MNBs enhance tissue quality as indicated by a significant increase in de novo adipogenesis, higher vessel density, and decreased adipocyte hypertrophy. Additional studies are needed to evaluate the clinical effectiveness. Nevertheless, incorporating MNBs into procedures holds great promise in tackling the ongoing challenge of inconsistent outcomes in lipotransfer.
Management of Delayed Vascular Occlusion in Free Flap Breast Reconstruction: A Systematic Review of Literature and Case Report
Authors: Uyulmaz Semra , Fontein Duveken , Sarvan Milos , Grünherz Lisanne , Giovanoli Pietro , Lindenblatt Nicole
Published: November 2024

Introduction

Free flap surgery is a reliable and safe procedure for breast reconstruction. The survival of free flaps depends on their vascular pedicle initially, but neovascularization can sustain their blood supply after a while. Management of late pedicle occlusion in free flap breast reconstruction and potential implications of late pedicle occlusion on the transferred tissue are controversial.

Methods and Materials

We systematically reviewed current literature focusing on articles that reported on late pedicle occlusion in free flaps for breast reconstruction. We aimed to analyze incidences of late pedicle occlusion, the existing evidence for the most appropriate management strategy for late pedicle occlusion, and its implications on overall outcomes. In support of the review, we present a clinical case of a salvage of a deep inferior epigastric artery perforator flap following late arterial thrombosis 12 days postoperatively.

Results

The literature is limited to a few case reports on pedicle occlusion in free flap breast reconstruction and a few heterogeneous retrospective reviews reporting on late pedicle occlusion in general. Despite the heterogeneity of articles and approaches to salvage flaps with late pedicle occlusion, we found no convincing evidence that surgery is the best choice to salvage flaps in breast reconstruction that appear to have late pedicle occlusion. Our case demonstrates that a conservative approach may be justified more than initially deemed necessary.

Conclusions

Late pedicle occlusion is a rare but serious event in free flap breast reconstruction. Surgery does not seem to be the most appropriate approach in every case. Decisions should be based on clinical dynamics and imaging findings such as indocyanine-green angiography. A carefully carried out conservative approach may lead to flap salvage.
Efficacy of Infliximab in Experimental Tracheal Stenosis
Authors: Yalinkiliç Abdulaziz , Yalinkiliç Fatma Ayaz , Beger Burhan , Erdem Mehmet Zeki , Uçar Hadice , Beger Orhan
Published: November 2024

Objective:

This study aimed to investigate the efficacy of infliximab, a TNF-α inhibitor, on epithelial damage, inflammation, and fibrosis in experimental tracheal stenosis.

Methods:

Rats were divided into 3 groups. In group 1 (the control group), no procedure was applied. Tracheotomy was opened in the other groups. The laryngotracheal mucosa of the rats was traumatized with a brush through the tracheostoma to create a stenosis model. After surgery, group 2 (the infliximab group) received 5 mg/kg infliximab intraperitoneally. In group 3 (the sham group) only 0.5 ml of saline (0.9% NaCl) was administered intraperitoneally. After 14 days, the rats were sacrificed. Tracheal rings were excised, and epithelial damage, inflammation, and fibrosis were evaluated histopathologically.

Results:

Infliximab reduced the formation of epithelial damage (P=0.002), fibrosis (P=0.001), and inflammation (P=0.003) compared with the sham and control group.

Conclusion:

This was the first investigation displaying the effects of infliximab on tracheal stenosis. The authors' experimental results may offer guidance for further studies. Their experience presents novel sights into optimizing outcomes in tracheal stenosis surgery, and so paves the way for further clinical examinations.
Mortality in people with mental disorders in Poland during the COVID-19 pandemic: a nationwide, register-based cohort study
Authors: Gondek Tomasz M. , Adamowski Tomasz , Janus Jolanta , Cichoń Ewelina , Paciorek Sylwia , Zięba Mariusz , Bukowska Alicja , Todzia-Kornaś Agata , Kiejna Andrzej
Published: November 2024

Purpose of review

People with mental disorders in Poland have increased standardized mortality ratios (SMRs). This is the first study to assess all-cause mortality in people with mental disorders in Poland during the COVID-19 pandemic.

Recent findings

A nationwide, register-based cohort study utilizing data from the registry of healthcare services (2011–2020) and the all-cause death registry (2021) in Poland was conducted. Individuals who were consulted or hospitalized in public mental healthcare facilities and received at least one diagnosis of mental disorders (ICD-10) from 2011 to 2020 were identified. SMRs were compared between people with a history of mental disorder and the general population. SMRs for the pandemic period were also compared with prepandemic SMRs calculated for 2019.

No significant differences in SMRs were observed overall between 2021 and 2019. A minor increase in SMR was observed in 2021 for people treated only in outpatient mental health clinics. In 2021, a significant decrease in SMRs was shown for individuals with diagnoses from groups F10-F19 and F20-F29, and a significant increase in SMRs was observed for those with diagnoses from group F40-F48.

SMRs for people with any mental disorder in Poland in 2021 remained at comparable levels to those in 2019.
The role of immunomodulators in severe mental disorders: future perspectives
Authors: Baune Bernhard T. , Fromme Sarah E.
Published: November 2024

Purpose of review

The immune system is of pivotal importance with regard to the development and maintenance of mental illness. Aberrant cytokine levels are significant immune markers, and research is increasingly focusing on the complement system and the gut-brain axis. The efficacy and safety of immunomodulatory interventions are currently the subject of clinical studies. Hence, this review is timeline and relevant to evaluate the latest evidence on the clinical value of immunomodulatory treatments from studies over the past 18 months in schizophrenia, bipolar disorder and unipolar depression.

Recent findings

While conventional psychotropic drugs (antidepressants, antipsychotics, lithium) appear to have immunomodulatory adverse effects, antibiotics (minocycline), nonsteroid anti-inflammatory drugs (celecoxib) and anti-inflammatory therapeutics in particular are the subject of ongoing clinical trials. Integrative medical interventions such as nutritional supplements (e.g., N-acetyl-l-cysteine, polyunsaturated fatty acids) and exercise interventions (e.g., running, yoga) are being evaluated for their immunomodulatory effects and clinical value.

No evidence-based recommendation can be made for the immunomodulatory treatment of depression, although celecoxib appears to be more effective than minocycline and omega-3 fatty acid. N-acetylcysteine (NAC) may be beneficial for the treatment of bipolar and schizophrenia disorders. However, further translational research is required to confirm these findings.
International Committee on Systematics of Prokaryotes Subcommittee on the Taxonomy of Mollicutes: minutes of the closed meeting, 7 July 2024, Gran Canaria, Spain
Authors: Gasparich Gail E. , Kuo Chih-Horng , Manso-Silván Lucia , Blanchard Alain , Balish Mitchell F.
Published: November 2024

A corrigendum of this article has been published full details can be found at

https://doi.org/10.1099/ijsem.0.006662

This report documents the International Committee on Systematics of Prokaryotes Subcommittee on the Taxonomy of Mollicutes minutes for the meeting held 7 July 2024, Gran Canaria, Spain, at the 25th International Organization for Mycoplasmology Congress.
Network meta-analysis on the effects of various exercise modalities on pain control in populations with chronic nonspecific low back pain
Authors: Zhao Ke , Li Hua , Li Li , li Yongxiao
Published: November 2024

Objective

This study aims to comprehensively evaluate and compare the effects of various exercise modalities on the control of chronic nonspecific low back pain through a network meta-analysis, in order to identify the most effective interventions.

Methods

Adhering strictly to the PRISMA guidelines, this study selected randomized controlled trials from databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus, up to June 30, 2024. Data were processed using Stata 17.0 software, and the effect sizes were synthesized using standardized mean differences (SMD) with 95% confidence intervals (CI). The SUCRA method was used to rank the effectiveness of the interventions.

Results

A total of 26 studies involving 1,507 participants aged between 20 and 63.5 years were included. The network meta-analysis revealed that yoga [SMD = −1.71 (−2.93, −0.49), P < 0.05] and core stability training [SMD = −0.81 (−1.44, −0.18), P < 0.05] were significantly more effective than the control group. SUCRA probability ranking indicated that Tai Chi (SUCRA = 77.4) might be the best modality for improving control of chronic nonspecific low back pain.

Conclusion

This network meta-analysis demonstrates the intervention effects of different exercise modalities on chronic nonspecific low back pain, with Tai Chi potentially being the most effective intervention. This provides an important reference for non-pharmacological interventions in chronic nonspecific low back pain.
Distinct Binding Modes of Inter-Spike Cross-Linking Suggest a Supplementary Mechanism for SARS-CoV-2 Antibody Neutralization
Authors: Nan Xuanyu , Li Yujie , Zhang Rui , Wang Ruoke , Lv Niannian , Li Jiayi , Chen Yuanfang , Zhou Bini , Wang Yangjunqi , Wang Ziyi , Zhu Jiayi , Chen Jing , Li Jinqian , Chen Wenlong , Zhang Qi , Shi Xuanling , Zhao Changwen , Chen Chunying , Liu Zhihua , Zhao Yuliang , Liu Dongsheng , Wang Xinquan , Yan Li-Tang , Li Taisheng , Zhang LinQi , Yang Yuhe R.
Published: November 2024

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their resistance to most neutralizing antibodies. Thus, exploring the mechanisms underlying antibody evasion is crucial. Although the full-length native form of antibody, immunoglobulin G (IgG), offers valuable insights into the neutralization, structural investigations primarily focus on the fragment of antigen-binding (Fab). Here, we employ single-particle cryo-electron microscopy (cryo-EM) to characterize a W328-6H2 antibody, in its native IgG form complexed with severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 wild-type (WT) and Omicron variant BA.1 spike protein (S). Three high-resolution structures reveal that the full-length IgG forms a centered head-to-head dimer of trimer when bound fully stoichiometrically with both SARS and WT S, while adopting a distinct offset configuration with Omicron BA.1 S. Combined with functional assays, our results suggest that, beyond the binding affinity between the RBD epitope and Fab, the higher-order architectures of S trimer and full-length IgG play an additional role in neutralization, elucidate a potential molecular basis of Omicron immune escape, and expand our understanding on antibody evasion mechanisms.
ER sensing of lipid metabolism drives PRA family-dependent regulation of COPII vesicle transport
Authors: Nakazato Mitsuki , Nakamura Hiroki , Kato Mei , Ikema Ryoko , Iguchi Mizuki , Hanaoka Kazuki , Eto Katsuki , Karashima Takefumi , Ikeda Asuko , Yabuki Yukari , Schlarmann Philipp , Manzano-Lopez Javier , Aguilera-Romero Auxiliadora , Sabido-Bozo Susana , Perez-Linero Ana Maria , Kanai Muneyoshi , Iefuji Haruyuki , Riezman Isabelle , Riezman Howard , Muñiz Manuel , Funato Kouichi
Published: November 2024

Newly synthesized secretory proteins and many lipids are transported from the endoplasmic reticulum (ER) to the Golgi prior to their ultimate destinations. The ER-to-Golgi transport must be tightly regulated during adaptation to environmental stress. However, the sensing mechanism and regulatory pathways governing the consecutive formation, budding and transportation of COPII vesicles from the ER remain insufficiently explored. Here, we present evidence indicating that COPII-mediated vesicle transport is transcriptionally controlled through the phosphatidic acid-dependent Opi1-Ino2/Ino4 regulatory circuit. Our analysis indicates thatYIP3, a target gene of Ino2/Ino4, exerts a negative regulatory impact on COPII-mediated vesicle transport. Furthermore, we demonstrated that Ino2/Ino4 but not Yip3 modulates Sar1 activation, the initial step in COPII vesicle formation, whereas Yip3 hinders Sec16 assembly on the ER membrane, thereby implying that Ino2/Ino4 governs COPII-mediated trafficking at multiple steps. Thus, this study provides the first evidence for an ER sensing system that transcriptionally fine-tunes multiple steps of anterograde vesicular transport in response to alterations in lipid composition of the ER membrane.
A global view of the RNA-binding and regulatory protein landscape inCaenorhabditis elegans
Authors: Laver John D. , Duncan Maida , Calarco John A.
Published: November 2024

Post-transcriptional regulation of gene expression is essential for the correct development and functioning of an organism. This regulation is coordinated by a collection of proteins that work together to determine an RNA’s post-transcriptional fate. Here, we provide a global overview of the RNA regulatory protein landscape inCaenorhabditis elegans, to provide insight into the coordination of post-transcriptional regulatory activities in the context of a multicellular organism. First, we have curated a comprehensive list of all known and putative RNA regulatory proteins encoded in theC. elegansgenome, classified based on domain and functional annotations and published experimental data. Second, using protein-protein interaction data in the STRING database, we created a putative RNA regulatory protein interaction network that highlighted known RNA regulatory complexes, and leveraged this network to identify an additional 138 known and putative RNA regulators previously unannotated inC. elegans. Finally, we examined the tissue- and developmental-stage-specific expression of RNA regulators using published transcript expression data, which revealed strong expression in the gonad for a majority, as well as dozens expressed specifically in each of the major somaticC. eleganstissues. Taken together, this work will provide a valuable resource for future studies of RNA biology inC. elegans.
Human activity, not environmental factors, drivesScedosporiumandLomentosporadistribution in Taiwan
Authors: Wu Hsin-Mao , Fan Yu-Hsuan , Phang Guan-Jie , Zeng Wen-Ting , El-Sayid Abdrabo Khaled Abdrabo , Wu Yu-Ting , Sun Pei-Lun , Lin Ying-Hong , Huang Yin-Tse
Published: November 2024

ScedosporiumandLomentosporaspecies are emerging fungal pathogens capable of causing severe infections in both immunocompetent and immunocompromised individuals. Previous environmental surveys have suggested potential associations between these fungi and various soil chemical parameters, though the relative influence of human activity versus environmental factors has not been systematically evaluated. Here, we conducted a comprehensive survey of 406 soil samples from 132 locations across Taiwan, analyzing fungal abundance alongside soil physicochemical parameters and the Human Footprint Index (HFI). We recovered 236 fungal isolates comprising 10 species, withS. boydii(32.2%),S. apiospermum(30.9%), andS. dehoogii(14.4%) being the most prevalent. The highest fungal burdens were observed in urban environments (up to 1293 CFU/g), particularly in public spaces and healthcare facilities. Statistical analysis revealed a significant positive correlation between fungal abundance and HFI (r = 0.125, p = 0.013), while soil chemical parameters including nitrogen, carbon, pH, electrical conductivity, and various base cations showed no significant associations despite their wide ranges. These findings indicate that anthropogenic disturbance of environments, rather than soil chemistry, is the primary driver ofScedosporiumandLomentosporadistribution in Taiwan. This understanding holds important implications for predicting infection risks and developing targeted public health strategies, particularly in rapidly urbanizing regions. Future studies incorporating more specific indicators of human impact may further elucidate the mechanisms underlying these distribution patterns.

Lay Abstract

We found that human activities, rather than soil properties, determine whereScedosporium/Lomentosporafungi distribute in Taiwan. These fungi are more abundant in urban areas than less-human-disturbed environments, suggesting increased infection risks in densely populated regions.
Dopamine D2receptor agonists abrogate neuroendocrine tumour angiogenesis to inhibit chemotherapy-refractory small cell lung cancer progression
Authors: Alam Sk. Kayum , Pandit Anuradha , Wang Li , Thiele Britteny A. , Manoj Parvathy , Aubry Marie Christine , Rudin Charles M. , Lo Ying-Chun , Hoeppner Luke H.
Published: November 2024

Small cell lung cancer (SCLC) is difficult to treat due to its aggressiveness, early metastasis, and rapid development of resistance to chemotherapeutic agents. Here, we show that treatment with a dopamine D2receptor (D2R) agonist reduces tumour angiogenesis in multiplein vivoxenograft models of human SCLC, thereby reducing SCLC progression. An FDA-approved D2R agonist, cabergoline, also sensitized chemoresistant SCLC tumours to cisplatin and etoposide in patient-derived xenograft models of acquired chemoresistance in mice.Ex vivo, D2R agonist treatment decreased tumour angiogenesis through increased apoptosis of tumour-associated endothelial cells, creating a less favourable tumour microenvironment that limited cancer cell proliferation. In paired SCLC patient-derived specimens, D2R was expressed by tumour-associated endothelial cells obtained before treatment, but D2R was downregulated in SCLC tumours that had acquired chemoresistance. D2R agonist treatment of chemotherapy-resistant specimens restored expression of D2R. Activation of dopamine signalling is thus a new strategy for inhibiting angiogenesis in SCLC and potentially for combatting chemotherapy-refractory SCLC progression.
In silicoIdentification of Novel Common Drug Targets Against Four InfectiousAcinetobacterSpecies
Authors: Rahman Soaibur , Hasnat Soharth , Mahbub M Murshida , Farzana Zinat , Sabila Sal
Published: November 2024

The global emergence of multidrug-resistantAcinetobacterspecies has become a major concern in the management of hospital-acquired infections. Moreover, misdiagnosis of one species ofAcinetobacterwith another has been reported, making it difficult to choose appropriate treatment. World Health Organization emphasizes the urgent need to develop new antibiotics to combatAcinetobacterinfections. This study aimed to discover novel common drug targets that will be effective againstAcinetobacter nosocomialis, Acinetobacter baumannii, Acinetobacter pittii,andAcinetobacter haemolyticus. We utilized a cluster-based subtractive genomics approach to identify potential drug targets. The main focus was to find drug targets that are absent in humans and essential for pathogens. We also performed metabolic pathway and subcellular localization analyses. Furthermore, protein structure-based studies and druggability analyses were conducted to identify viable therapeutic options. Out of 1245 protein clusters (minimum 4 proteins/cluster), 204 clusters were human non-homologous and essential for bacteria. Among them, 39 clusters were cytoplasmic and involved in unique metabolic pathways which are specific to the pathogens. After analyzing the drug target sequences of DrugBank database, 12 clusters were found to be novel drug targets. Eventually, proteins of one cluster were identified as advantageous drug targets having drug-binding pockets at very similar regions with high druggability scores. These proteins can be inhibited to disrupt the Lysine/DAP biosynthetic pathway ofAcinetobacter.Our research might open up a new possibility for drug discovery against these pathogens.
Ligand-independent c-Met activation by HHLA2 drives hepatocellular carcinoma and predicts c-MET inhibitor efficacy
Authors: Huang Xubo , Fang Runya , Pang Yuqian , Zhang Zhe , Huang Jieru , Li Yingchang , Yuan Tao , Zeng Yuyi , Yao Ziying , Vega-Rubín-de-Celis Silvia , Thinwa Josephine , Shen Hao , Wang Jiahong , Shen Feng , Wei Yongjie
Published: November 2024

The HGF/c-Met signaling pathway facilitates the initiation, progression, and metastasis of hepatocellular carcinoma (HCC). c-Met activation, however, is complex and not solely dependent on HGF, hindering targeted therapy development. This study identifies a critical oncogenic role for HHLA2, a B7 family member, in HCC and highlights its potential as a therapeutic target. We demonstrate that HHLA2 directly interacts with and activates c-Met through N-glycosylation, triggering sustained signaling and promoting aggressive HCC features. Mechanistically, we identified the pro-tumorigenic role of HHLA2 required downstream upregulation of MMP9 and VEGFA, both implicated in tumor progression. In multiple mouse models, HHLA2 overexpression accelerated tumor progression, metastasis, and reduced liver NK cell infiltration, all of which were reversed by c-Met inhibition. In a cohort of 176 HCC patients, HHLA2 expression strongly correlated with c-Met phosphorylation, advanced tumor stage, and poor prognosis. Importantly, HHLA2 expression predicted sensitivity to c-Met inhibitors in cell lines and patient-derived organoids and could be detected in patient serum, suggesting its potential as a prognostic biomarker. Collectively, our findings reveal an HHLA2-mediated mechanism of c-Met activation and provide a strong rationale for targeting the HHLA2-c-Met axis as a novel therapeutic strategy, with HHLA2 serving as a potential prognostic biomarker.

Abstract Figure
A negative feedback loop between small GTPase Rap1 and mammalian tumor suppressor homolog KrsB regulates cell-substrate adhesion inDictyostelium
Authors: Artemenko Yulia , Niu Gengle , Arnold Megan E. , Roberts Kelsey E. , Fernandez Bianca N. , Flores Tiffany , McClave Harper D. , Paestella Michael , Borleis Jane , Devreotes Peter N.
Published: November 2024

Cell adhesion to the substrate influences a variety of cell behaviors and its proper regulation is essential for migration, although details of the molecular pathways regulating cell adhesion during migration are lacking. Rap1 is a small GTPase that regulates adhesion in mammalian cells, as well as inDictyostelium discoideumsocial amoeba, which is an established model for studying directed cell migration. InDictyostelium, Rap1 controls adhesion via its effects on adhesion mediator talin and Ser/Thr kinase Phg2, which inhibits myosin II function. Kinase responsive to stress B (KrsB), a homolog of mammalian tumor suppressor MST1/2 andDrosophilaHippo, also regulates cell adhesion and migration, although the molecular mechanism of KrsB action is not understood. Since KrsB has been shown to interact with active Rap1 by mass spectroscopy, we investigated the genetic interaction between Rap1 and KrsB. Cells lacking KrsB have increased adhesion to the substrate, which leads to reduced movement. Expression of constitutively active Rap1 G12V increased cell spreading and adhesion even in the absence of KrsB, suggesting that Rap1 does not require KrsB to mediate cell adhesion. In contrast, dominant negative Rap1 S17N completely reversed the over-adhesive phenotype of KrsB-null cells and impaired KrsB phosphorylation, suggesting that KrsB activation and function in adhesion requires Rap1. Even though Rap1 did not require KrsB for its function in adhesion, KrsB negatively regulates Rap1 function as seen by increased cortical localization of Rap1 in KrsB-null cells. Consistent with this, chemoattractant-induced activation of downstream effectors of Rap1, TalB and Phg2, was increased in the absence of KrsB. Taken together, these findings suggest that Rap1 leads to activation of KrsB, which inhibits Rap1 and its downstream targets, shutting off adhesion. The existence of a negative feedback loop between Rap1 and KrsB may contribute to the dynamic regulation of cell adhesion that is necessary for rapid amoeboid-type migration.