bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of patients with autoimmune pancreatitis and IgG4-related disease without pancreas involvement
Authors: Mack Sahar , Nigolian Haïg , Ricoeur Alexis , Bornand Aurélie , Beniada Camille , Bichard Philippe , Seebach Jörg Dieter , Frossard Jean-Louis
Published: January 2025

OBJECTIVES:

The objective of this retrospective observational study was to compare patients diagnosed with autoimmune pancreatitis (AIP) and IgG4-related disease (IgG4-RD) without pancreatic involvement, and to evaluate their clinical presentation, treatment modalities, and outcomes.

METHODS:

Data were retrospectively collected from January 2010 to January 2022, including clinical presentation, imaging findings, histological and immunological characteristics, and treatment outcomes.

RESULTS:

In 11 patients with AIP, the most common symptom was abdominal pain (54.5%), while seven of these patients (63.6%) presented other organ involvement. Initial treatment with steroids was administrated to 10 patients, with a relapse rate of 72.8% over a mean follow-up of 5.3 months. Four patients required additional rituximab therapy. Of the 22 patients with IgG4-RD without AIP, the majority had ear, nose, and throat (ENT) involvement (45.5%). Patients with AIP had higher serum IgG4 levels. Fifteen patients (68.2%) were treated with prednisone, six underwent surgery (27.3%), and four received symptomatic treatment only (18.2%) with a relapse rate of 36.4%. Six patients were treated with rituximab.

CONCLUSION:

AIP and IgG4-RD are increasingly recognized conditions, with steroid being the standard of care. Although our clinical and imaging findings are consistent with previous reports, our patients had a higher relapse rate, highlighting the importance of vigilant monitoring and potentially evolving treatment strategies.
Status of a New Model of ERCP Training in China
Authors: Zhang Di , Cai Yi-Li , Yi Jin-Hui , Xu Mao-Jin , Xin Lei , Lv Yan-Wei , Lin Xi , Yang Huai-Yu , Jin Zhen-Dong , Wang Dong , Liao Zhuan , Wang Luo-Wei , Hu Liang-Hao , Li Zhao-Shen
Published: January 2025

Aims:

ERCP training should adapt to the rapid development of ERCP technology and indications. China has a large population and vast land area, but ERCP training resources are insufficient. To make effective use of scarce ERCP training resources, the Standardized Training for ERCP Procedure (STEP) program was launched as a pilot trial. We aimed to report the graduation and competence situations and analyze the predictive factors.

Methods:

This was a prospective multicenter study from January 2015 to May 2021 containing 2 stages: the training program stage and the graduate questionnaire survey stage. The graduation and competence rates were investigated and analyzed.

Results:

In the training stage, 146 trainees completed the training, 113 (77.4%) graduated. The gender ratio (men vs. women) was 6.7:1. The mean age was 40.14±4.13 years. In total, 11 trainees failed the institutional mentored training phase (IMTP), 18 failed the practice strengthen training phase (PSTP), and 4 failed the comprehensive theoretical test. In the questionnaire survey stage, the response rate was 92%, of which 76.9% (80/104) achieved competence. ERCP cases performed independently in IMTP (OR=1.129, P=0.025) and ERCP volume in training years (OR=1.018, P=0.026) were predictive factors for graduation. Job title (senior physician) (OR=78.811, P=0.018) and main practice form of PSTP (independently) (OR=17.062, P=0.031) were predictive factors for competence in available graduates.

Conclusions:

The STEP achieved an acceptable graduation and competence rate. We gained valuable experience in framework organization and multiple assessment checkpoints. Therefore, this standardized training model is suitable for developing countries with rapid progress in ERCP.
Successfully treated esophageal gastrointestinal stromal tumor by minimally invasive esophagectomy followed by imatinib therapy: a case report
Authors: Doan Tu Trong , Pham Duong The , Nguyen Cuong Van , Tran Thanh Tuan , Nguyen Hai Van
Published: January 2025

Introduction:

Gastrointestinal stromal tumor (GIST) is a common malignancy of the gastrointestinal tract, but rarely occurs in the esophagus, composing approximately 0.7% of all GISTs. Surgery is a mainstay treatment for this disease. We herein report a case of a 68-year-old male patient treated by thoraco-laparoscopic esophagectomy followed by imatinib therapy for a large esophageal GIST, and also review a literature regarding this disease.

Case report:

A 68-year-old male was admitted to our hospital due to dysphagia. After the initial investigations, the patient was diagnosed with esophageal GIST and underwent thoraco-laparoscopic esophagectomy. Final immunohistochemistry (IHC) was positive with CD117, CD34, DOG-1, Ki67 without the expression of SMA, S-100 that confirmed GIST. The patient was referred to adjuvant therapy with imatinib and there was no recurrence at 16 months after surgery.

Discussion:

Due to the rarity of esophageal GISTs, diagnosis and treatment remain challenging. Without immunohistochemistry, this disease may be misdiagnosed as esophageal leiomyoma, or with other mesenchymal tumors such as sarcoma or schwannoma due to similar clinical, endoscopic and radiographic characteristics. Surgery is the cornerstone treatment, the choice of enucleation or esophagectomy depends on the comprehensive evaluation of clinical and pathologic factors of the specific case. Neoadjuvant or adjuvant treatment with imatinib is an effective therapy for selective patients.

Conclusion:

GISTs are rare neoplasms of the esophagus. Currently, surgical resection is the cornerstone treatment, adjuvant or neoadjuvant therapy with imatinib may be indicated for selective patients. Clinical trials are expected with longer follow-ups to develop concrete guidelines for this disease.
Rheumatoid arthritis: a comprehensive overview of genetic markers, emerging therapies, and personalized medicine
Authors: Shakeel Laiba , Shaukat Ayesha , Khaliq Nawal , Kashif Aayat , Mujeeb Azka , Adnan Zahabia , Taj Javeria , Akilimali Aymar
Published: January 2025

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder marked by chronic inflammatory arthritis and systemic effects. The etiology of RA is complex, involving genetic factors like HLA-DR4 and HLA-DR1, as well as environmental influences, particularly smoking, which heightens disease risk. Affecting approximately 1% of the global population, RA is associated with considerable morbidity and mortality, with its prevalence expected to increase due to demographic shifts, especially in certain regions. RA symptoms commonly manifest between ages 35 and 60 but can also affect children under 16 in cases of juvenile RA. Symptoms include prolonged joint stiffness, pain, fatigue, and, in advanced cases, joint deformities. Current treatment approaches involve disease-modifying antirheumatic drugs, biologics, and glucocorticoids to manage symptoms and slow disease progression, though these treatments often present limitations due to adverse effects and varied patient response. The identification of genetic markers, such as HLA-DRB1 and PTPN22, supports the growing emphasis on personalized treatment strategies that account for genetic and lifestyle factors. Non-pharmacological approaches – diet adjustments, physical activity, and stress management – are increasingly valued for their complementary role in RA management. Lifestyle interventions, including whole-food, plant-based diets and physical therapy, show promise in reducing inflammation and improving joint function. Technological advancements, like telemedicine, mobile health applications, and artificial intelligence, are enhancing RA diagnosis and treatment, making care more precise and accessible. Despite these advancements, RA remains incurable, necessitating continued research into novel therapeutic targets and approaches. A comprehensive, patient-centered approach that integrates lifestyle modifications, preventive strategies, and innovative treatments is essential for improving RA management and patient outcomes.
A rare case of inferior vena cava interruption and pulmonary valve stenosis in the absence of heterotaxy syndrome
Authors: Rajab Tuqa , Abou Nukta Moayad , Bannoud Nour , Haddad Sultaneh , Aljarmakani Dimah , Ali Doaa Mukhtar Mohammed , Jama Amal Mohamed H. Hassan , Srour Samir
Published: January 2025

Introduction:

The complete absence hepatic portion of the inferior vena cava (IVC) is known as “interruption” of the IVC. Congenital interruption of the IVC can rarely occur in patients with a normal visceroatrial situs.

Case presentation:

We present a case of an 8-year-old male child who exhibited mild dyspnea. Further evaluation revealed an interruption of the IVC and pulmonary valve stenosis, without heterotaxy.

Discussion:

It is important to recognize that interruption of the IVC can occur independently or as part of a syndrome. Therefore, thorough investigations should be conducted for each patient.

Conclusion:

More research is needed to explore the associations between IVC interruption and pulmonary valve stenosis.
Management of preoperative anxiety with non-pharmacological methods in pediatric patients in resource-limited settings: a literature review
Authors: Achule Astemamagn , Gedeno Kanbiro , Aweke Zemedu
Published: January 2025

Background:

Anxiety disorders are common in children and among the most prevalent psychiatric issues. Untreated preoperative anxiety can lead to increased complications and a higher risk for future anxiety disorders and major depression. Therefore, addressing preoperative anxiety in children is crucial to prevent perioperative and long-term adverse effects.

Objective:

This review aimed to evaluate various articles and develop a management plan based on evidence for the prevention of preoperative anxiety in children using non-pharmacological approaches in areas with limited resources.

Methods:

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Databases, such as PubMed, Cochrane Library, and Google Scholar, were searched for high-quality evidence to draw appropriate conclusions.

Result:

A total of 7669 articles were retrieved from the search engines. These articles were then filtered based on intervention, outcome, population data, inclusion and exclusion criteria, and methodological quality. After the filtration process, only 35 studies met the inclusion criteria for comprehensive review.

Conclusion:

The Children’s Emotional Manifestation Scale (CEMS) effectively assesses preoperative anxiety in children. Evidence suggests that non-pharmacological interventions such as clowning, music therapy, audiovisuals, virtual reality, and cognitive-behavioral therapy are effective in preventing preoperative anxiety. Practitioners can choose a suitable non-pharmacological approach based on availability and cost.
Unilateral amelia with limb deformities and multiple congenital malformations in a newborn: a case report from Palestine
Authors: Oweidat Majd , Alra’e Mohammed , Aldwaik Mohammed , Shubietah Abdalhakim
Published: January 2025

Introduction:

Unilateral amelia, a rare congenital anomaly characterized by the absence of one limb, is often accompanied by severe malformations in other systems. Although the survival of affected infants beyond the neonatal period is rare, some cases have been documented with varying outcomes. This case report discusses a newborn with unilateral amelia and multiple congenital anomalies.

Presentation of case:

A 41-week gestation stillbirth from Palestine was delivered after a normal pregnancy, except for prenatal ultrasound findings of absent left upper limb, severe lower limb deformities, preaxial polydactyly, syndactyly, dextrocardia, and asymmetric hydrocephalus. Postnatal examination revealed additional craniofacial anomalies, gastrointestinal malformations, and respiratory abnormalities. Despite the severe deformities, the infant survived beyond 2 months.

Discussion:

Unilateral amelia is often associated with other congenital malformations, indicating complex embryological disruptions. The combination of limb deficiency with visceral abnormalities complicates management and prognosis. While stillbirths and early neonatal deaths are common, this case’s survival beyond 2 months is a notable exception. This report contributes valuable insight into the prognosis of such rare congenital conditions.

Conclusion:

This case emphasizes the rarity of unilateral amelia with multiple congenital defects and underscores the importance of comprehensive prenatal evaluation and genetic counseling. The patient’s extended survival provides new perspectives on the management and outcomes of infants with such complex anomalies.
Intravenous Pump Flow Accuracy: A Systematic Review
Authors: Blake Jeannine W.C.
Published: January 2025

Intravenous pumps (IVPs) deliver IV medications to millions of acute care patients each year and result in many adverse events reported to the US Food and Drug Administration (FDA). Although the use of IVPs has improved overall safety, there are still high rates of error that risk the safety of all patients, especially those of advanced age and those suffering from critical illness. Most of the documented errors are based on clinician reports, although there is reason to believe that errors due to flow rate inaccuracy go undetected and unreported. The purpose of this systematic literature review was to explore literature regarding flow rate accuracy for IVPs used in US acute care medicine. The systematic review was conducted by searching PubMed, CINHAL, and Web of Science. Articles chosen were from any year, written in the English language, and had content pertaining to the use of IVPs and key concepts of interest. Concepts discussed throughout the literature are relevant to the IVPs used for patient care, including outlet pressure, intake pressure, dead volume, and pump setup. This review provides a conceptual overview of what is known about this technology but reveals a gap in knowledge related to actual IVP clinical accuracy.
How Does the Normalization Process After the COVID-19 Pandemic Affect Patients With Obsessive-Compulsive Disorder? A Longitudinal Study
Authors: Gökçen Onur , Akkuş Merve
Published: January 2025

This study aims to investigate the effect of the normalization process after the pandemic on obsessive-compulsive disorder (OCD) patients. During the pandemic period, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Padua Inventory–Washington State University Revision, the Fear of COVID-19 Scale (FCV-19S), and an interview form inquiring sociodemographic characteristics were applied to the participant patients with OCD. During the normalization process, the patients were reevaluated after about 1 year. A significant decrease was found in the patients' FCV-19S and PE-WSUR total scores along with all subscale scores as well as the Y-BOCS scores. The FCV-19S was associated with OCD symptoms both during the pandemic and the normalization period. The final FCV-19S scores of patients with a Y-BOCS score of 12 and under were found to be statistically significantly lower than the others. This study shows that OCD symptom severity and fear of COVID-19 decreased with the normalization process. A decrease in pandemic-related stress and fear of COVID-19 with the normalization process may have positively affected OCD patients.
Follicular Helper T-cell Lymphoma With Hodgkin/Reed-Sternberg–Like Cells Versus Classic Hodgkin Lymphoma
Authors: Petronilho Sara , Poullot Elsa , Andre Axel , Robe Cyrielle , Nouhoum Sako , Fataccioli Virginie , Quintela José Miguel , Claudel Alexis , Brière Josette , Lechapt Emmanuele , Lemonnier François , Henrique Rui , de Leval Laurence , Gaulard Philippe
Published: January 2025

Lymphomas of T-follicular helper origin (T-follicular helper–cell lymphoma [TFHL]) are often accompanied by an expansion of B-immunoblasts, occasionally with Hodgkin/Reed-Sternberg-like (HRS-like) cells, making the differential diagnosis with classic Hodgkin lymphoma (CHL) difficult. We compared the morphologic, immunophenotypic, and molecular features of 15 TFHL and 12 CHL samples and discussed 4 challenging cases of uncertain diagnosis. Compared with CHL, TFHL disclosed more frequent sparing of subcortical sinuses, high-endothelium venule proliferation, dendritic cell meshwork expansion, T-cell atypia, and aberrant T-cell immunophenotype. HRS-like and HRS cells were CD30+, often CD15+ and EBV infected. There was a variable loss of B-cell markers in both diseases, with an expression of CD20, CD79a, CD19, or OCT-2 more frequently preserved in HRS-like cells of TFHL. The T-cell infiltrate was predominantly CD4+/CD8-, with expression of at least 2 TFH-markers in all TFHL and 75% of CHL. The most useful TFH marker was CD10 (positive in 86% TFHL and no CHL). Twelve/15 TFHL contained CD30+ neoplastic TFH cells, whereas CD30 expression was mostly restricted to HRS cells in CHL. We detected monoclonal TR rearrangements in 75% of TFHL and no CHL; and monoclonal IG rearrangements in 23% of TFHL and 42% of CHL. All TFHL had TET2 mutations; 13/14 presented RHOA mutations, 3 accompanied by DNMT3A and 1 DNMT3A+IDH2 mutations. Three CHL had TET2 mutations, likely attributable to clonal hematopoiesis. Our study further underlines that HRS(-like) cells are not pathognomonic of CHL. Since no single pathologic criterion distinguishes TFHL and CHL, an integrative approach ideally comprising molecular investigations is fundamental.
Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma
Authors: Skálová Alena , Bradová Martina , Agaimy Abbas , Laco Jan , Badual Cécile , Ihrler Stephan , Damjanov Ivan , Rupp Niels J. , Bacchi Carlos E. , Mueller Sarina , Ventelä Sami , Zhang Da , Comperat Eva , Martínek Petr , Šíma Radek , Vaněček Tomas , Grossmann Petr , Steiner Petr , Hájková Veronka , Kovářová Inka , Michal Michal , Leivo Ilmo
Published: January 2025

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB, or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC. We have searched the authors’ registries and selected all AdCCs arising in the sinonasal tract. The tumors were examined histologically, immunohistochemically, by next generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) looking for MYB/MYBL1 and/or NFIB gene fusions or any novel gene fusions and/or mutations. In addition, all tumors were tested for HPV by genotyping using (q)PCR. Our cohort comprised 88 cases of sinonasal AdCC, predominantly characterized by canonical MYB::NFIB (49 cases) and MYBL1::NFIB (9 cases) fusions. In addition, noncanonical fusions EWSR1::MYB; ACTB::MYB; ESRRG::DNM3, and ACTN4::MYB were identified by NGS, each of them in 1 case. Among nine fusion-negative AdCCs, FISH detected rearrangements in MYB (7 cases), NFIB (1 case), and EWSR1 (1 case). Six AdCCs lacked fusions or gene rearrangements, while 11 cases were unanalyzable. Mutational analysis was performed by NGS in 31/88 (35%) AdCCs. Mutations in genes with established roles in oncogenesis were identified in 21/31 tumors (68%), including BCOR (4/21; 19%), NOTCH1 (3/21; 14%), EP300 (3/21; 14%), SMARCA4 (2/21; 9%), RUNX1 (2/21; 9%), KDM6A (2/21; 9%), SPEN (2/21; 9%), and RIT1, MGA, RB1, PHF6, PTEN, CREBBP, DDX41, CHD2, ROS1, TAF1, CCD1, NF1, PALB2, AVCR1B, ARID1A, PPM1D, LZTR1, GEN1, PDGFRA, each in 1 case (1/21; 5%). Additional 24 cases exhibited a spectrum of gene mutations of uncertain pathogenetic significance. No morphologic differences were observed between AdCCs with MYBL1::NFIB and MYB::NFIB fusions. Interestingly, mutations in the NOTCH genes were seen in connection with both canonical and noncanonical fusions, and often associated with high-grade histology or metatypical phenotype, as well as with poorer clinical outcome. Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.
Aesthetic Reconstruction of Huge Full-Thickness Defection of Lower Eyelid Using Nasolabial Mucosal-Myocutaneous Propeller Flap
Authors: Zhang Yu , Zhang Xi , Chen Jie
Published: January 2025

Reconstruction after the excision of a lower eyelid tumor should be focused on the restoration of both functionality and aesthetic appeal. Accurate identification and appropriate intervention are crucial for the favorable resolution of the condition. This technique used a nasolabial mucosal-myocutaneous propeller flap to reconstruct a huge full-thickness defection of right lower eyelid because of basal cell carcinoma. Therefore, the nasolabial mucosal-myocutaneous propeller flap displayed an excellent adaptation to the orbital structure, ensuring high graft survivability, and yielding an aesthetically pleasing outcome with negligible morbidity at the donor site. This case serves as an important reminder to choose the nasolabial mucosal-myocutaneous propeller flap, which was viable and could be applied to reconstruct the skin, tarsus, and palpebral conjunctiva at a time.
Investigating Racial, Ethnic, and Socioeconomic Disparities in Pelvic Organ Prolapse Surgery
Authors: DeAndrade Samantha , DePorto Krystal , Crawford Kaitlin , Saporito Lucas , Nguyen AnMarie , Yazdany Tajnoos , Tenggardjaja Christopher
Published: January 2025

Importance

Racial/ethnic and socioeconomic disparities have been observed in the mode of pelvic organ prolapse surgery. Some of the disparities may be attributed to differences in access to care and advanced surgical technology across the United States, although this is difficult to study.

Objective

We aimed to investigate whether racial/ethnic or socioeconomic disparities in a mode of prolapse surgery exist in a managed care setting, where differences in access are minimized.

Study Design

This was a retrospective cohort study of patients who underwent apical pelvic organ prolapse surgery within Kaiser Permanente Southern California facilities between 2014 and 2017. We conducted bivariate tests to examine the associations between patient characteristics and multivariate logistic regression to predict the odds of having obliterative and native tissue repair surgical procedures by race and income.

Results

The analytic sample consisted of 2,798 patients who underwent prolapse surgery. Hispanic/Latina, Non-Hispanic White, Non-Hispanic Black, Asian, and “other” race represented 51.1%, 37.0%, 5.7%, 5.3%, and 0.8% of the sample, respectively. Median household income varied by racial groups. After adjusting for patient characteristics and regional factors, we did not find significant differences in apical prolapse surgery mode by race/ethnicity or income level.

Conclusions

Within this managed care setting, no disparities in mode of apical prolapse surgery were observed by race/ethnicity or income level when regional and patient-level confounders were controlled for, such as prolapse stage and comorbidities. This may suggest that a significant driver of racial/ethnic disparities observed in prolapse surgery may be attributed to structural level factors.
National analysis of health-related social needs among adult injury survivors
Authors: Hernandez Alexandra H. , Clark Nina M. , Bisgaard Erika , Nehra Deepika , Stewart Barclay T. , Malloy Alexander , Bulger Eileen M. , Dieleman Joseph L. , Zatzick Douglas , Scott John W.
Published: January 2025

BACKGROUND

Despite advances in trauma care, the effects of social determinants of health continue to be a barrier to optimal health outcomes. Health-related social needs (HRSNs), now the basis of a Centers for Medicare and Medicaid Services national screening program, may contribute to poor health outcomes, inequities, and low-value care, but the impact of HRSNs among injured patients remains poorly understood at the national level.

METHODS

Using data from the nationally representative 2021 Medical Expenditure Panel Survey, injured patients were matched with uninjured controls via coarsened exact matching on age and sex. We then determined the prevalence of HRSNs based on core needs identified by Centers for Medicare and Medicaid Services: food, utilities, living situation, transportation, and personal safety. We used multivariable regression models to evaluate the association between HRSNs and health, delays in care, and emergency department visits.

RESULTS

Overall, 43% of injured patients reported one or more HRSNs. Compared with uninjured controls, injured patients were more likely to have unmet needs in all five HRSN domains (adjusted odds ratio, 1.44–2.00; p < 0.05 for all). In stratified analyses, HRSNs were highest among patients with lower income (65.1%), those who identified as Non-Hispanic Black patients (61.3%), and patients with Medicaid (66.1%). Increasing number of HRSNs was associated with worse physical and mental health (p < 0.05). Injured patients with three or more HRSNs were also more likely to delay care because of cost (adjusted odds ratio, 3.79; 95% confidence interval, 2.29–6.27) and had greater emergency department utilization (adjusted incidence rate ratio, 1.47; 95% confidence interval, 1.16–1.87).

CONCLUSION

In this nationally representative study, nearly half of injured patients had one or more HRSNs. Greater numbers of HRSNs were associated with worse health outcomes, delayed care, and low-value care. As national screening for HRSNs is implemented, strategies to address these factors are needed and may serve to optimize health and health care utilization among injury survivors.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Exploring the genomic landscape of Chlamydiifrater species: Novel features include multiple truncated major outer membrane proteins (MOMP), unique genes, and chlamydial plasticity zone orthologs
Authors: Hölzer Martin , Reuschel Charlotte , Vorimore Fabien , Laroucau Karine , Sachse Konrad
Published: January 2025

Recently discovered obligate intracellular bacteria belonging to the genus Chlamydiifrater (Cf.) with the species of Cf. phoenicopteri and Cf. volucris were studied to explore the composition of their genomes and their relatedness to Chlamydia, the other genus of the family Chlamydiaceae.
We investigated four isolates of Cf. volucris, two of them newly sequenced, and one of Cf. phoenicopteri alongside 12 representatives of the Chlamydia species. Our study uncovers previously unrecognized genomic structures within Cf. using a hybrid sequencing approach and advanced annotation pipelines, providing insights into species-specific adaptations and evolutionary dynamics. The integration of long-read sequencing data, comprehensive re-annotation strategies, and pan-genomics enabled localization of the unique plasticity zone and identification of novel gene clusters in Chlamydiifrater strains, which improves our understanding of chlamydial genome architecture and plasticity in the family Chlamydiaceae. Our analysis revealed that 761 CDS (approx. 80 %) are shared among members of both genera. We further identified 158 unique genes of Cf. species but their annotation remains challenging because of the absence of functionally annotated orthologs in public databases. A full-length ompA gene encoding the major outer membrane porin (MOMP) was seen in all Cf. strains. We also describe the localization and structure of multiple truncated CDS of ompA family members, representing one of this study's most interesting findings.
While genome analysis of Chlamydiifrater spp. confirmed numerous common features shared with representatives of the genus Chlamydia, many unique genomic elements were identified that underpin the distinct phenotype and separate genetic position of these new microorganisms.
Altered gut microbial profiles in drug-treated rats with alcoholic heart disease
Authors: Wei Siang , Feng Yan , Meng Ai , Ding Zhiwen , Lin Wenji
Published: January 2025

Introduction. Alcohol abuse can lead to significant cardiac injury, resulting in Alcoholic heart disease (AHD). The interplay between cardiac health and gut microbiota composition in the context of alcohol consumption is not well understood.

Hypothesis. Shen Song Yang Xin (SSYX) capsule and amiodarone are common drugs used to treat alcoholic heart disease, but little is known about their microbial regulatory mechanisms in alcoholic heart disease.

Aim. To investigate the effects of SSYX and amiodarone on cardiac injury and gut microbiota composition in a rat model of AHD induced by alcohol consumption.

Methodology. We evaluated body weight, cardiac function, changes in gut morphology, and gut microbiota composition to assess the effects of SSYX and amiodarone on AHD.

Results. Alcohol consumption significantly reduced body weight and aggravated cardiac fibrosis. However, SSYX attenuated fibrosis and improved cardiac function. SSYX also improved intestinal morphological changes caused by chronic alcoholism and activated the expression of ZO-1 and occludin, which are important in maintaining intestinal barrier function. The gut microbiota composition was altered in rats with AHD, with an increase in Actinobacteria abundance. Both SSYX and amiodarone affected the gut microbiota composition, and their effects were positively correlated. SSYX plays a protective role against heart injury caused by alcohol consumption. It improves cardiac function, intestinal morphological changes and gut microbiota composition.

Conclusion. SSYX and amiodarone may have potential therapeutic options for AHD. Actinobacteria/Firmicutes ratio and the abundance of Christensenellaceae R7 group, norank_flachnospiraceae and Roseburia may serve as potential biomarkers for detecting alcoholic heart disease.
Directionality of two-photon absorption in representative fluorescent proteins
Authors: Lazar Josef , Timr Štěpán , Rybakova Olga , Brynda Jiří , Thuen Adam , Drobizhev Mikhail , Myšková Jitka
Published: January 2025

Molecules of fluorescent proteins (FPs) exhibit anisotropic optical properties. While the directionality of single-photon (1P) absorption and emission in the most commonly used FPs has already been characterized, directionality of their two-photon (2P) excitation remains poorly understood, even though it offers higher sensitivity to molecular orientation and promises to yield more information on molecular orientational distributions than the 1P processes. By measuring optical properties of FP crystals, we have now determined the two-photon absorptivity tensors (2PATs) of the FPs mTurquoise2, eGFP and mCherry. Our results demonstrate the feasibility of experimental 2PAT determinations, provide new insights into molecular mechanisms of 2P absorption in FPs, open a new avenue to rational development of novel biosensors and allow detailed structural interpretation of results obtained with such biosensors.
TOR and heat shock response pathways regulate peroxisome biogenesis during proteotoxic stress
Authors: Shukla Nandini , Neal Maxwell L. , Farré Jean-Claude , Mast Fred D. , Truong Linh , Simon Theresa , Miller Leslie R. , Aitchison John D. , Subramani Suresh
Published: January 2025

Peroxisomes are versatile organelles mediating energy homeostasis and redox balance. While peroxisome dysfunction is linked to numerous diseases, the molecular mechanisms and signaling pathways regulating peroxisomes during cellular stress remain elusive. Using yeast, we show that perturbations disrupting protein homeostasis including loss of ER or cytosolic chaperone function, impairments in ER protein translocation, blocking ER N-glycosylation, or reductive stress, cause peroxisome proliferation. This proliferation is driven by increasedde novobiogenesis from the ER as well as increased fission of pre-existing peroxisomes, rather than impaired pexophagy. Notably, peroxisome biogenesis is essential for cellular recovery from proteotoxic stress. Through comprehensive testing of major signaling pathways, we determine this response to be mediated by activation of the heat shock response and inhibition of Target of Rapamycin (TOR) signaling. Finally, the effects of proteotoxic stress and TOR inhibition on peroxisomes are also captured in human fibroblasts. Overall, our findings reveal a critical and conserved role of peroxisomes in cellular response to proteotoxic stress.
Iterative acylation on mature lasso peptides by widespread acetyltransferases for lipolasso production
Authors: Xiong Jiang , Wu Shanquan , Liang Zi-Qi , Fang Shuo , Tao Fen-Yu , Gong Xiao-Tong , Wu Qingfeng , Cui Jiao-Jiao , Gao Kun , Luo Shangwen , Lei Dongsheng , Dong Shi-Hui
Published: January 2025

The biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs) leverages iterative catalysis to enhance structural and biological diversity. Traditionally, iterative enzymes install multiple post-translational modifications (PTMs) on linear peptides, rather than mature RiPPs with intricate three-dimensional structures, which would require complex changes in substrate binding poses. Here, we present a prolific class of GCN5-related N-acetyltransferases (GNATs) that iteratively and consecutively acylate two Lys residues within the loop and ring motifs of lasso peptides, diverging from the typical iterative modification of linear peptides—an unprecedented function for PTM enzymes. Utilizing high-resolution cryo-electron microscopy and enzymatic reconstitution, we mapped the lasso peptide binding pocket of IatT and pinpointed key residues involved in demarcating the two distinct acetylation steps. Structure-based engineering of IatT’s acetyl group recognition site expanded the cavity to accommodate longer-chain acyl groups, leading to the creation of lipolasso peptides, a novel class of ribosomal lipopeptide. This engineering strategy can be applied to any RiPP BGC encoding GNAT, facilitating the efficient diversification of rare ribosomal lipopeptides.

Graphic Abstract
Single-cell and spatial transcriptomics uncover the role of B chromosomes in driving plant invasiveness
Authors: Wang Cui , Ord James , Yan Mengxiao , Shao Hongjin , Lin Lele , Salojärvi Jarkko , Liu Lele , Guo Weihua
Published: January 2025

Invasive plants can profoundly disrupt native biodiversity, yet the genetic mechanisms underpinning their success remain poorly understood. To date, genomic studies have been conducted on only a limited number of invasive species, and no single-cell level studies have been applied. This research investigates the genetic drivers behind the invasive behavior of the common reed (Phragmites australis), a hardy grass species that became invasive in North America following its introduction from Europe. By integrating whole-genome sequencing with single-cell and spatial transcriptomics, we developed a comprehensive single-cell atlas of the common reed’s shoot system. UMAP analysis identified 19 distinct cell clusters within the shoot system. Gene Ontology (GO) enrichment enabled the annotation of key cell types, including mesophyll, epidermal, bundle sheath, and xylem cells, as well as shoot apical and lateral bud meristems, and auxillary meristems. RNA velocity analysis highlighted the multipotent nature of mesophyll cells, with chlorenchyma in Cluster 3 identified as progenitor cells capable of differentiating into various tissues and Cluster 1 progressing towards aerenchyma formation. Comparative analysis between European and North American invasive populations revealed significant differences in transcriptional activity and gene expression, particularly in clusters associated with the shoot apical meristem. Invasive populations exhibited a higher prevalence of B chromosomes, with three genes IMPA-3, SSC3, and DDE family endonuclease gene consistently upregulated across nearly all clusters, notably near mesophyll and meristematic regions. The fast mutation in IMPA-3 which functions as a major receptor of Resistance (R) gene may have strengthened the adaptability of the invasive population in North America. These findings provide critical insights into the cellular development and genomic diversity underlying the invasiveness of the common reed, offering valuable information to guide ecological management strategies.
Structure of theThomasclavelia ramosaimmunoglobulin A protease reveals a modular and minimizable architecture distinct from other immunoglobulin A proteases
Authors: Tran Norman , Frenette Aaron , Holyoak Todd
Published: January 2025

Immunoglobulin A proteases (IgAPs) are a diverse group of enzymes secreted from bacteria that inhabit human mucosal tissues. These enzymes have convergently evolved to cleave human immunoglobulin A as a means of modulating and evading host immunity. Only two of three known IgAP families have been biochemically characterized beyond their initial discovery. Here, we show using solution-scattering, steady-state kinetic, and crystallographic approaches that the protease fromThomasclavelia ramosa, representing the uncharacterized third family, has a truly modular and minimizable protein architecture. This analysis also revealed a unique metal-associated domain that likely functions as a molecular spacer and generated a working hypothesis detailing the structural mechanism behind the enzyme’s high substrate specificity. Our work provides the first in-depth biochemical account of this IgAP family, paving the way for advancing clinically relevant IgAP-related research and our understanding of IgAPs as a whole.
Circuit dynamics of approach-avoidance conflict in humans
Authors: Staveland Brooke R. , Oberschulte Julia , Kim-McManus Olivia , Willie Jon T. , Brunner Peter , Dastjerdi Mohammad , Lin Jack J. , Hsu Ming , Knight Robert T.
Published: January 2025

Debilitating anxiety is pervasive in the modern world. Choices to approach or avoid are common in everyday life and excessive avoidance is a cardinal feature of all anxiety disorders. Here, we used intracranial EEG to define a distributed prefrontal-limbic circuit dynamics supporting approach and avoidance. Presurgical epilepsy patients (n=20) performed an approach-avoidance conflict decision-making task inspired by the arcade game Pac-Man, where participants trade-off real-time harvesting rewards with potential losses from attack. As patients approached increasing rewards and threats, we found evidence of a limbic circuit mediated by increased theta power in the hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), which then drops rapidly during avoidance. Theta band connectivity between these regions increases during approach and falls during avoidance, with OFC serving as a connector in this circuit with high theta coherence across limbic regions, but also with regions outside of the limbic system, including the lateral prefrontal cortex. Importantly, the degree of OFC-driven connectivity predicts how long participants approach, with enhanced network synchronicity extending approach times. Finally, under ghost attack, the system dynamically switches to a sustained increase in high-frequency activity (70-150Hz) in the middle frontal gyrus (MFG), marking the retreat from the ghost. The results provide evidence for a distributed prefrontal-limbic circuit, mediated by theta oscillations, underlying approach-avoidance conflict.
Molecular basis for the activation ofPseudomonas aeruginosaMsbA by Zn2+
Authors: Lyu Jixing , Bahramimoghaddam Hanieh , Zhang Tianqi , Yadav Gaya P. , Zhao Minglei , Russell David , Laganowsky Arthur
Published: January 2025

Proteins involved in the biogenesis of lipopolysaccharide (LPS), a lipid exclusive to Gram-negative bacteria, are promising candidates for drug discovery. Specifically, the ABC transporter MsbA plays a crucial role in translocating an LPS precursor from the cytoplasmic to periplasmic facing leaflet of the inner membrane, and small molecules that inhibit its function exhibit bactericidal activity. Here, we use native mass spectrometry (MS) to determine lipid binding affinities of MsbA fromP. aeruginosa(PaMsbA), a Gram-negative bacteria associated with hospital-acquired infections, in different conformations. We show the ATPase activity of the transporter is stimulated by Zn2+and successfully trapping the protein with vanadate requires Zn2+not Mg2+, which is necessary to trap MsbA fromE. coli. We also present cryogenic-electron microscopy structures of PaMsbA in occluded and open outward-facing conformations determined to a resolution of 2.98 and 2.72 angstroms, respectively. The structures reveal a triad of histidine residues and mutation of these residues abolishes Zn2+stimulation of PaMsbA activity. Together our studies provide detailed insight into PaMsbA structure, lipid binding preferences, and uncover a mechanism through which Zn2+promotes the dimerization of the transporter, resulting in enhanced ATPase activity.
Spore morphology and evolution inIsoetes(Isoetales)
Authors: Larsén Eva , Khodabandeh Anbar , Rydin Catarina
Published: January 2025

Isoetes(Isoetaceae, Isoetales) is a cosmopolitan genus with an ancient and diverse evolutionary history that presumably peaked in the Paleozoic. The age of the living clade has never been satisfactorily clarified. With little morphological (and molecular) divergence among species, megaspore morphology may provide valuable information on relationships in the group, not least among extant and extinct forms. We study megaspore ornamentation and surface texture/structure in 74 phylogenetically placed samples representing 59 species ofIsoetesusing SEM, and we discuss evolutionary implications of the results. Ornamentation (classified into 12 categories) and surface structure/texture (10 categories) were mapped onto a phylogeny constructed based on molecular data from the same samples whenever possible. All megaspores of the family are trilete with an outermost siliceous coating. There is ample micromorphological variation, of which some appears clade specific. The megaspores ofIsoetes reticulata, discovered from the late Oligocene to early Miocene of Tasmania, share remarkable similarities with those of extant species in the Australasian clade, in particularIsoetes neoguineensisand partly alsoIsoetes japonica. We argue that this fossil could be used to calibrate the age of the Australasian crown group (clade D) to absolute time (c. 20-25 Ma) in analyses of divergence times of clades based on molecular data.
Ethanol induces craniofacial defects in Bmp mutants independent ofnkx2.3by elevating cranial neural crest cell apoptosis
Authors: Vo Hieu , Lovely C. Ben
Published: January 2025

Background

Fetal Alcohol Spectrum Disorders (FASD) describes a wide range of neurological defects and craniofacial malformations associated with prenatal ethanol exposure. While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Endoderm morphogenesis to form lateral protrusions called pouches is one key mechanism in facial development. We have previously shown that multiple members of the Bone Morphogenetic Pathway (Bmp) signaling pathway, a key regulator of pouch formation, interacts with ethanol disrupting facial development. However, ethanol does not directly impact Bmp signaling suggesting that downstream effectors, likenkx2.3may mediate the impact of ethanol on Bmp mutants.

Methods

Here we use an ethanol exposure paradigm withnkx2.3knockdown approaches to test if loss ofnkx2.3sensitizes Bmp mutants to ethanol induced facial defects. We then combine a morphometric approach with Hybridization Chain Reaction and immunofluorescence to examine the cellular mechanisms underlying Bmp-ethanol interactions.

Results

We show that Bmp-ethanol interactions alter morphology of the endodermal pouches, independent ofnkx2.3gene expression. Morpholino knock down ofnkx2.3does not sensitize wild type orbmp4mutant larvae to ethanol-induced facial defects. However, we did observe a significant increase CNCC apoptosis in ethanol-treated Bmp mutants.

Conclusions

Collectively, our results suggest that ethanol’s mode of action is independent of downstream Bmp effectors, converging on CNCC cell survival. Ultimately, our work provides a mechanistic paradigm of ethanol-induced facial defects and connects ethanol exposure with concrete cellular events.
Assessment of awareness and attitudes of pregnant women toward labor epidural analgesia and factors influencing the decision to opt for it: A cross-sectional study
Authors: Kassa Adugna A. , Sahle Wossenyeleh A. , Desalew Tsehaynew , Lakew Zufan , Behabtu Tigist
Published: January 2025

Background

Epidural analgesia is one of the most effective forms of pain relief during various stages of labor. Despite its many advantages, the technique is not routinely practiced in most centers in developing countries. Awareness and attitudes toward it, as well as the reasons for its limited utilization, have not been explored in our setting.

Therefore, the aim of this study was to assess the awareness and attitudes of pregnant women toward labor epidurals and to assess the factors influencing their decision to receive labor epidural analgesia (LEA) during labor and delivery.

Methods

A cross-sectional study was conducted from June to August 2024 at Hemen Medical Center. A structured questionnaire was used to collect the data. The collected data were analysed via SPSS version 26. Descriptive statistics were used to summarize the descriptive results, and logistic regression was employed to identify factors associated with the decision to receive labor epidural analgesia during delivery. A p value of < 0.05 was used to determine statistical significance.

Results

Two hundred thirty pregnant women, with a mean age of 30 ± 4.3 years, were included in the analysis. Approximately 78% of the participants had heard of labor epidural analgesia (LEA), although only 6.5% reported healthcare providers as their primary source of information. Approximately 47% believed that LEA was effective for pain relief during labor. However, only 14.3% expressed a willingness to consider using LEA during delivery. Education level, family income, perceived risk to the Fetus, and perceived effectiveness in relieving pain were identified as factors influencing the decision to consider LEA during delivery.

Conclusion

Despite relatively high basic awareness of LEA, many participants remain hesitant to utilize it during labor and delivery. Comprehensive health education and counselling during antenatal care are essential to address misconceptions and promote informed decision-making regarding LEA.