bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing complexities in β-thalassemia care: a case series from a resource-limited setting
Authors: Adhikari Pratik
Published: September 2024

Introduction and importance:

β-thalassemia is a hereditary blood disorder with a global prevalence, presenting diagnostic and management challenges, particularly in regions with high consanguinity rates. Diagnostic methods include clinical assessments, genetic testing, and hemoglobin electrophoresis. Treatment typically involves transfusions and chelation therapy, with gene therapy showing promise. This case series emphasizes the need for tailored care strategies and global health initiatives to improve outcomes for β-thalassemia patients worldwide.

Methods:

This case series involves five patients from rural Nepal presenting various β-thalassemia manifestations. The cases highlight the challenges in diagnosis and management in resource-limited settings. Data were collected through clinical assessments, laboratory investigations, and follow-ups. Each patient’s medical history, presentation, and treatment regimen were documented.

Outcomes:

The cases underscore the importance of regular follow-ups, community engagement, and personalized treatment strategies tailored to genetic profiles. Key findings include the necessity for consistent transfusion schedules, iron overload monitoring, and managing complications associated with β-thalassemia. Enhanced education and healthcare collaboration were noted as critical for optimizing care and outcomes in resource-limited settings.

Conclusions:

Managing β-thalassemia in resource-limited settings demands timely intervention, regular monitoring, and community involvement. Enhanced healthcare collaboration, access to advanced diagnostic tools, and tailored treatment strategies are paramount in addressing the unique challenges of β-thalassemia. These measures are essential for ensuring an improved quality of life for affected individuals in such regions.
The glutamatergic system in the development of stress-induced depression
Authors: Wei Xinran
Published: September 2024

Major depression is one of the most prevalent neuropsychological disorders and affects millions worldwide. In response, the monoaminergic system has been proposed to be one of the major focuses for conventional drugs in the treatment of depression, such as selective serotonin reuptake inhibitor (SSRI). Meanwhile, accumulating evidence suggests a paradigm shift from the monoamine system towards the glutamatergic system (Gerard Sanacora, Giulia Treccani, and Maurizio Popoli 2012) due to the long onset of the monoamine system targeting anti-depressant drugs. Both clinical and pre-clinical data support that glutamatergic system dysfunction were involved in the development of depression. Furthermore, therapeutic approaches that manipulating neuronal activity and N-methyl-D-aspartic acid (NMDA) receptor antagonist were shown to have profound effects in the treatment of depression. Here, I systematically reviewed our current understanding of the involvement of glutamatergic system dysregulation in the development of depression, which potentially could provide the mechanistic basis for future treatment development.
Understanding disparities in cardiovascular death rates among older adults with sick sinus syndrome in the US
Authors: Hameed Ishaque , Nusrat Khushboo , Farhan Syed H. , Ahmad Oneeb , Hameed Indallah , Malik Shanza , Shaikh Ali T. , Raja Adarsh , Aijaz Ashnah , Arham Siddiq Muhammad , Saleem Patel Mustafa , Khan Rafay , Sharma Varsha , Hussain Muzna
Published: September 2024

Background:

Sick sinus syndrome (SSS) increases with age, and approximately one in 600 patients above 65 develop this condition. In this study, the authors assessed trends in mortality related to SSS among older adults ≥65 years of age in the United States from 1999 to 2019.

Methods:

Trends in cardiovascular mortality related to SSS were identified by analyzing the data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, where cardiovascular deaths were listed as the underlying cause of death and SSS was listed as the contributing cause of death between 1999 and 2019. Age-adjusted mortality rates (AAMR) per 1,000,000 population were determined.

Results

Between 1999 and 2019, a total of 41,615 SSS-related deaths occurred in older adults. Of these, 17,466 (41.9%) were men and 24,149 (58.1%) were women. Although a decline in cardiovascular mortality related to SSS was apparent from 1999 to 2014, a steep rise was noted from 2014 to 2019 [Annual Percentage Change (APC): 2.9%; 95% CI, 1.5–5.7]. Overall AAMRs were highest among White men (AAMR: 55.8; 95% CI, 54.9–56.6), followed by Black men (AAMR: 44.8; 95% CI, 42–47.6), White women (AAMR: 43.3; 95% CI, 42.8–43.9), and Black women (AAMR: 39.4; 95% CI, 37.6–41.2). Rural dwellers had higher AAMRs compared to urban dwellers. Notably, rural dwellers had a period of stability between 2014 and 2019, while an increase in mortality was apparent among urban dwellers during this period. Lastly, states in the 90th percentile displayed approximately two fold higher AAMR compared to those in the bottom 10th percentile.

Conclusion:

Sick sinus syndrome-related mortality trends have shown a steady rise from 2014 to 2019. Moreover, NH White adults, rural dwellers, and individuals residing in the states among the 90th percentile demonstrated significantly higher AAMRs. Thus, further investigations and actions are required to reverse these rising trends.
Chiari malformation and its influence on trigeminal neuralgia: a systematic review
Authors: Badary Amr , Almealawy Yasser F. , Florez-Perdomo William A. , Sanker Vivek , Andrew Awuah Wireko , Abdul-Rahman Toufik , Salam Alabide Arwa , Alrubaye Sura N. , Saleh Aalaa , Ergen Anil , Chaurasia Bipin , Azab Mohammed A. , Atallah Oday
Published: September 2024

Objective:

In order to properly understand the correlation between TN and Chiari malformation type I (CMI), it is imperative to delve into the underlying processes and develop efficacious treatment strategies.

Methods:

A comprehensive search was performed regarding trigeminal neuralgia (TN) in individuals diagnosed with CMI. A total of 19 cases were identified in the existing literature.

Results:

The review of 19 studies showed that the most commonly affected division was V2 (31.6%), followed by V3 (10.5%) and V1 (5.3%). Radiological findings were variable. The medulla oblongata was compressed in 6 patients (31.6%), the cervical spinal cord showed abnormalities in 3 patients (15.8%) abnormalities; one cervical myelocele (5.26%), two cervical syringomyelia (10.53%) while 5 patients (26.3%) showed normal findings. The skull bones in 4 patients (21,1%) showed deformity in the form of small posterior fossa or platybasia. The surgical treatment was conducted in 14 patients (73.7%). The study suggested that posterior fossa decompression (PFD) plus microvascular decompression (MVD) dual surgical modality yielded the best results for V2 distribution (P=0.017).

Conclusion:

Chiari malformation type I can directly influence the occurrence and severity of trigeminal neuralgia. Therefore, an effective management of this malformation, like neurovascular decompression, PFD or ventriculoperitoneal shunt, can act as a potential treatment for trigeminal neuralgia. While the PFD alone was effective in the V3 and V1 distribution of trigeminal neuralgia, PFD plus microvascularplus plus microvascular decompression (MVD) as a dual surgical modality yielded the best results for V2 distribution.
Rare clinical presentation of a ruptured spinal bulbomedullary arteriovenous malformation: a case report
Authors: Vega-Moreno Daniel A. , Molina-Martínez Rodolfo P. , Aburto-Murrieta Yolanda , Méndez-González Beatriz , Reyes-Soto Gervith , Serrano-Murillo Mónica , García-González Ulises , Chaurasia Bipin
Published: September 2024

Introduction and importance:

Spinal arteriovenous malformations (AVMs) are a rare condition that has a high risk of bleeding and complications. The authors present the case of a spinal arteriovenous malformation in an unusual location and presentation.

Case presentation:

A 67-year-old man with subarachnoid hemorrhage due to a ruptured spinal arteriovenous malformation type IVa, with associated bulbomedullary aneurysm, which was managed conservatively due to the high risk of complications and mortality.

Clinical discussion:

Spinal AVMs have had different management and treatments over the years, so conservative management remains an option when arterial cannulation is complex and surgery carries a high risk of complications.

Conclusion:

Due to the high risk of complications of surgery in this location, conservative treatment is an option for the management of such cases with good outcomes.
Exploring the need for surgical face masks in operating room: a comprehensive literature review
Authors: Abbass Mortada , Kotaich Jana , Ziade Karl , Sleiman Yara , Olleik Hanine , Nasrallah Inaam , Obeid M. Baker , Moussa Mohamad
Published: September 2024

Surgical face masks (SFM) are pivotal in preventing surgical site infections (SSI) in the operating room (OR). However, there are currently no specific recommendations for their most effective use. SFM effectiveness is influenced by factors such as material, fit, and duration of use, sparking ongoing debates about their benefits and risks in surgery. SFMs act as a protective barrier, but their ability to filter out harmful compounds is questioned. They can also impact communication and create a false sense of security. Nevertheless, SFMs aid in infection prevention and provide psychological comfort. Clear guidelines are needed to ensure their appropriate use in the OR. This paper offers a historical overview of surgical masks, emphasizing their role in infection prevention. It explores SFM effectiveness for both the surgical team and patients during surgery and considers their future in surgical settings. As we navigate the evolving landscape of SFMs, clear and concise guidelines are imperative to ensure their judicious and effective use in the OR. This paper serves as an essential resource for understanding the historical significance, contemporary efficacy, and prospective trajectory of SFMs in surgical practice.
Medial augmentation of distal femur fractures using the contralateral distal femur locking plate: A technical note
Authors: Leal Jaime Andrés
Published: September 2024

Introduction:

Lateral locking plates are commonly employed for the fixation of distal femur fractures. However, scenarios involving medial comminution, extremely distal fractures, periprosthetic fractures, or nonunion could necessitate medial augmentation. This study explores the possibility of using lateral distal femoral locking plate systems for medial fixation by employing the contralateral plate.

Methods:

This study presents a technical note on the application of lateral distal femur locking systems for medial augmentation in patients as indicated by current literature findings. Postoperative imaging modalities, including radiography and computed tomography (CT), were used to assess the plates' fit to the distal femur. Three cases following the specified technical note are presented.

Results:

The various plate systems, all comprising distal femur locking systems, demonstrated adaptability to the medial femur anatomy as confirmed by intraoperative visualization and postoperative radiographs, including two-dimensional and three-dimensional CT scans. It has also been possible to achieve at least 3 independent fixation points regardless of the size of the medial condyle.

Conclusions:

Locking distal femoral plates can be a viable option for medial augmentation in indicated cases, achieving anatomical adaptation to the distal femur. This provides robust augmentation without the need for additional instruments beyond those used for the lateral cortex.
Conduction System Hamartoma
Authors: Keskin Ozturk Beyza , Gun Eylul
Published: September 2024

Conduction system hamartoma is a benign hamartomatous lesion arising from Purkinje and Purkinje-like cells of the heart. We aimed to investigate the cases that we detected during postmortem histopathological examination. The histopathology reports of the cases autopsied between 2012 and 2022 were reviewed retrospectively. The cases were evaluated in terms of histopathological features, demographic data, autopsy findings, causes of death, microbiological results, and accompanying cardiac anomalies. There was a total of 4 cases. The female-to-male ratio was 3/1. The mean age of the cases was 5.8 months. The heart weight was found within the normal range when evaluated according to age and gender. Microscopy revealed sharply demarcated cell groups or layers with histiocyte-like cells with foamy cytoplasm. Congenital heart disease and lung infection were given as causes of death in all cases. The lesion, which was previously called histiocytoid cardiomyopathy and many different names, is known as “conduction system hamartoma” in the latest World Health Organization classification (5th edition). Being aware of this entity that causes fatal arrhythmias and sudden cardiac deaths is important for pathologists. Autopsy findings should be evaluated by taking extra samples from the heart if necessary, especially in suspected cases below 2 years of age.
The Thuss Lectureship Series at Vanderbilt University
Authors: James Andrew J. , Lineaweaver William C.
Published: September 2024

Background

The Thuss lectureship began in 1978 and is carried at both Vanderbilt University Medical Center and Stanford Medical Center. The 2-day event consists of a resident and fellow workshop and dinner with an invited keynote speaker, followed by a didactic session and research presentation the following morning. This lecture honors the career of Dr Charles J. Thuss, Sr, and acts as a memorial for Dr Thuss, Jr, and his son, Carter. Trainee presentations have been catalogued since 2019, and we sought to identify the presentations that resulted in publications.

Methods

Internal records from 2019 to 2022 were referenced to catalogue presenters and project titles. PubMed searches were conducted to identify projects from these presenters with direct links to their presentations at the lectureship series.

Results

The event has been held consecutively from 1978 to 2023 with 44 keynote lecturers. Between 2019 and 2023, 17 residents, fellows, and medical students from Vanderbilt University Medical Center or/and the Tennessee Society of Plastic Surgery gave 19 research presentations for the Thuss lectureship at Vanderbilt. Due to the pandemic, no resident or trainee presentations were given in 2020. Nine of 11 project presentations resulted in publications, with presenters being the resultant first author of 6 of these articles.

Conclusion

The Thuss lectureship at Vanderbilt serves as an academic conduit to share research and build camaraderie among plastic surgeons across Tennessee. Additionally, it fosters a platform for trainees to contribute to the academic literature and see projects from inception to publication.
Current Diagnostic Measures for Lymphedema
Authors: Torres-Guzman Ricardo A. , Bailey Virginia , James Andrew J. , Drolet Brian C. , Karagoz Huseyin
Published: September 2024

Lymphedema presents diagnostic challenges due to complex symptomatology and multifaceted onset. This literature review synthesizes diagnostic measures ranging from clinical assessments to advanced imaging techniques and emerging technologies. It explores the challenges in early detection and delves into the disparities in access to advanced diagnostic tools, which exacerbate health outcome differences across populations. This review not only provides insights into the effectiveness of current diagnostic modalities but also underscores the necessity for ongoing research and innovation. The goal is to enhance the accuracy, affordability, and accessibility of lymphedema diagnostics. This is crucial for guiding future research directions and for the development of standardized diagnostic protocols that could help mitigate the progression of lymphedema and enhance the quality of life for affected individuals.
Multiple organ failure: What you need to know
Authors: Brakenridge Scott , Kornblith Lucy , Cuschieri Joseph
Published: September 2024

Multiple organ failure (MOF) remains a significant challenge for the acute care surgeon, often leading to poor patient outcomes. This comprehensive review explores the etiology, pathophysiology, clinical presentation, diagnosis, management strategies, prognosis, and prevention strategies associated with MOF and chronic critical illness. Understanding the intricate etiology and pathophysiology of MOF and chronic critical illness is essential for effectively managing these syndromes and developing targeted treatment strategies aimed at mitigating the underlying inflammatory, immune, and microvascular disturbances, in order to redirect patients onto a trajectory of recovery.
Perimortem cesarean section after severe injury: What you need to know
Authors: Larson Nicholas J. , Mergoum Anaas Moncef , Dries David J. , Hubbard LeeAnn , Blondeau Benoit , Rogers Frederick B.
Published: September 2024

When pregnant patients are involved in traumatic incidents, the trauma clinician encounters two patients—both the mother and the unborn child. Advanced trauma life support dictates that the first priority is the life of the mother; however, there are rare situations where to provide the greatest chance of survival for both the mother and baby, an emergency cesarean section (perimortem cesarean delivery [PMCD]) must be performed. The decision to perform this procedure must occur quickly, and the reality is that a board-certified obstetrician is rarely present, particularly in rural areas. In this review, we provide a rationale for why trauma clinicians should be conversant with PMCDs, present the specific time limitations for performing a PMCD, and discuss the technique to perform a successful PMCD that makes it distinctly different from an elective cesarean delivery. Finally, we will discuss some things that a trauma program can do proactively in an obstetrical resource-poor area of the country to prepare for the rare instances where these procedures are necessary.
Prognosis, risk factors, and scoring model of patients resuscitated from traumatic cardiac arrest: A multicenter observational study in Japan
Authors: Shibahashi Keita , Inoue Ken , Kato Taichi , Sugiyama Kazuhiro
Published: September 2024

BACKGROUND

A subset of patients with traumatic cardiac arrest is salvageable when the reversible causes of cardiac arrest are promptly treated. However, prognosis and risk factors of survivors upon hospital admission after traumatic cardiac arrest remain unclear. We aimed to describe the outcomes, identify risk factors, and develop a simple risk-scoring model for patients resuscitated from traumatic cardiac arrest.

METHODS

This observational multicenter study analyzed data from the Japan Trauma Data Bank from January 1, 2019, to December 31, 2021. Patients who underwent cardiopulmonary resuscitation in the emergency department and survived to the day after hospital admission for traumatic cardiac arrest were included. Factors associated with survival to hospital discharge were determined using mixed-effects multivariable logistic regression analysis. A simple scoring model was developed to stratify the probability of survival to hospital discharge.

RESULTS

In total, 452 patients from 119 hospitals (median age, 64 years; 334 [74.4%] men) were included in the analysis. Of these, 130 (28.8%) survived until discharge. Penetrating injury, signs of life upon hospital arrival, and Injury Severity Score were significantly associated with survival at hospital discharge. A scoring model that assigned 1 point each for penetrating injury and signs of life upon hospital arrival effectively stratified the probability of survival to hospital discharge, with scores of 0, 1, and 2 corresponding to survival probabilities of 12.2%, 35.2%, and 83.3%, respectively.

CONCLUSION

This study described the outcomes and risk factors of patients resuscitated from traumatic cardiac arrest. Our simple scoring model effectively stratified the likelihood of survival to hospital discharge.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Identification of Salmonella enterica biovars Gallinarum and Pullorum and their antibiotic resistance pattern in integrated crop-livestock farms and poultry meats
Authors: Julianingsih Dita , Alvarado-Martinez Zabdiel , Tabashsum Zajeba , Tung Chuan-Wei , Aditya Arpita , Kapadia Sarika , Maskey Saloni , Mohapatra Aditi , Biswas Debabrata
Published: September 2024

Due to consumer demand, many conventional poultry farms are now growing poultry without antibiotics or synthetic chemicals. In addition to this, pasture/organic poultry farms have increased significantly in the USA, and they are also antibiotic- and chemical-free. According to recent reports, both antibiotic-free conventional and pasture poultry farmers are facing the reemergence of bacterial diseases. Bacterial diseases cause higher mortality rates in birds and lead to non-profitable poultry farming. This study investigated the prevalence of Salmonella enterica subsp. enterica serovar Gallinarum biovars Gallinarum (S. Gallinarum), the causative agent of fowl typhoid, and Salmonella enterica subsp. enterica serovar Gallinarum biovars Pullorum (S. Pullorum), the causative agent of pullorum disease, within integrated crop-livestock/pasture farm environments and their processed products. A total of 1,286 samples were collected from 6 farms and adjacent 13 markets to determine the prevalence of S. Gallinarum and S. Pullorum by using both microbiological culture and molecular techniques. Antibiotic resistance pattern of the confirmed isolates was subsequently determined with an antibiogram assay following the Clinical Laboratory Standards Institute guidelines for relevant antibiotics. S. Pullorum was detected in 11 samples (2.7%), while S. Gallinarum was found in 6 samples (1.5%) out of a total of 403 samples at the pre-harvest level. At the post-harvest level, only S. Gallinarum was identified in 14 meat samples out of 883 (1.6%) recovered from samples collected from retail markets. Antibiogram showed S. Gallinarum and S. Pullorum to be highly resistant to cephradine, trimethoprim-sulfamethoxazole, amoxicillin, streptomycin, and ampicillin. This data demonstrates that both S. Pullorum and S. Gallinarum are commonly present in farm poultry environments as well as the products sold in the markets, which warrants implementation of regular surveillance and monitoring programs, as well as potentially requiring future control strategies to reduce S. Pullorum and S. Gallinarum transmission.
The Y498T499-SARS-CoV-2 Spike (S) protein interacts poorly with rat ACE2 and does not affect the rat lung.
Authors: Green Amy L , Debellis Dylan , Cowell Evangeline , Lenchine Roman V , Penn Timothy , Kris Luke P , McEvoy-May James , Bihari Shailesh , Dixon Dani-Louise , Carr Jillian M
Published: September 2024

The rat is a useful laboratory model for respiratory disease, and SARS-CoV-2 proteins such as the spike (S) protein can induce inflammation. This study has investigated the ability of the Q498Y, P499T (QP-YT) amino acid change described in the S-protein of the mouse adapted laboratory SARS-CoV-2 MA strain, to interact with rat angiotensin converting enzyme-2 (ACE2) and stimulate responses in rat lung. Using a real-time S-ACE2 quantitative fusion assay, ancestral and L452R S-protein fuses with human, but not rat ACE2 expressed on HEK293 cells. The QP-YT S-protein retains ability to fuse with human ACE2, and increases binding to rat ACE2. Although rat lower lung contains both ACE2 and TMPRSS2 target cells, intratracheal delivery of ancestral or QP-YT S-protein pseudotyped lentivirus did not induce measurable respiratory changes, inflammatory infiltration, or innate mRNA responses. Isolation of primary cells from rat alveoli demonstrated the presence of cells expressing ACE2 and TMPRSS2. Infection of these cells, however with ancestral or QP-YT S-protein pseudotyped lentivirus was not observed and the QP-YT S-protein pseudotyped lentivirus poorly infected HEK293 cells expressing rat ACE2. Analysis of the amino acid changes across the S-ACE2 interface highlights the Y498 interaction with H353 as a likely facilitator of binding to rat ACE2 but also other amino acids that could improve this interaction.
Thus, rat lungs contain cells expressing receptors for SARS-CoV-2 and the QP-YT S-protein variant can bind to rat ACE2 but this does not result in infection or stimulate responses in the lung. Further amino acid changes in S-protein could enhance this interaction to improve the utility of the rat model for defining the role of the S-protein in driving lung inflammation.
Routine blood parameters as auxiliary diagnostic tools for Mycoplasma pneumoniae infection in children
Authors: Qiu-ju Chu , Ling-yu Gao , Ting-dong Zhou , Yang Tong , Ning Han , Ai-hua Wang , Huai-lou Hu , Qiang Zhou , Bing Chen
Published: September 2024

Introduction. Recently, the incidence of Mycoplasma pneumoniae (M. pneumoniae) infection in children has been increasing annually. Early differential diagnosis of M. pneumoniae infection can not only avoid the abuse of antibiotics, but also is essential for early treatment and reduction of transmission.

Gap statement. The change of routine blood parameters may have important clinical significance for the diagnosis of M. pneumoniae infection, but it has not been reported so far.

Aim. This study aims to establish a predictive model for M. pneumoniae infection and explore the changes and clinical value of routine blood parameters in children with M. pneumoniae infection, serving as auxiliary indicators for the diagnosis and differentiation of clinical M. pneumoniae infection.

Methodology. A total of 770 paediatric patients with respiratory tract infections were enrolled in this study, including 360 in the M. pneumoniae group, 40 in the SARS-CoV-2 group, 200 in the influenza A virus group, and 170 in the control group. The differences of routine blood parameters among all groups were compared, and risk factors were analysed using multivariate logistics analysis, and the diagnostic efficacy of differential indicators using ROC curves.

Results. This study revealed that Mono% (OR: 3.411; 95% CI: 1.638–7.102; P=0.001) was independent risk factor associated with M. pneumoniae infection, and Mono% (AUC=0.786, the optimal cutoff at 7.8%) had a good discriminative ability between patients with M. pneumoniae infection and healthy individuals. Additionally, Mono% (OR: 0.424; 95% CI: 0.231–0.781; P=0.006) and Lymp% (OR: 0.430; 95% CI: 0.246–0.753; P=0.003) were independent risk factors for distinguishing M. pneumoniae infection from influenza A virus infection, and the Lymp% (AUC=0.786, the optimal cutoff at 22.1%) and Net% (AUC=0.761, the optimal cutoff at 65.2%) had good discriminative abilities between M. pneumoniae infection and influenza A infection. Furthermore, platelet distribution width (OR: 0.680; 95% CI: 0.538–0.858; P=0.001) was independent risk factor for distinguishing M. pneumoniae infection from SARS-CoV-2 infection. Meanwhile, the ROC curve demonstrated that PDW (AUC=0.786, the optimal cutoff at 15%) has a good ability to differentiate between M. pneumoniae infection and SARS-CoV-2 infection.

Conclusion. This study demonstrates that routine blood parameters can be used as auxiliary diagnostic indicators for M. pneumoniae infection and provide reference for the diagnosis and differentiation of clinical M. pneumoniae infection.
A spatial atlas of human gastro-intestinal acute GVHD reveals epithelial and immune dynamics underlying disease pathophysiology
Authors: Azulay Nofar , Milo Idan , Bussi Yuval , Uri Raz Ben , Haran Tal Keidar , Eldar Michal , Elhanani Ofer , Harnik Yotam , Yakubovsky Oran , Nachmany Ido , Salame Tomer-Meir , Wartenberg Martin , Bertheau Philippe , Michonneau David , Socie Gerard , Keren Leeat
Published: September 2024

Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplantation (aHSCT), driven by alloreactive donor T cells in the gut. However, the roles of additional donor and host cells in this process are not fully understood. We conducted multiplexed imaging on 59 biopsies from patients with gastrointestinal GVHD and 10 healthy controls, revealing key pathological changes, including fibrosis, crypt alterations, loss of Paneth cells, accumulation of endocrine cells, and disrupted immune organization, particularly a reduction in IgA-secreting plasma cells. Interestingly, CD8T cells were enriched only in a subset of patients, while others exhibited non-canonical enrichments of macrophages and neutrophils. Post-transplantation time significantly influenced immune composition, with host cells dominating plasma and T cell compartments long after transplantation. This spatial atlas of healthy duodenum and GVHD uncovers non-canonical immune dynamics, offering insights into disease pathophysiology and potential clinical applications in GVHD and other inflammatory bowel diseases.
Power asymmetry destabilizes reciprocal cooperation in social dilemmas
Authors: Colnaghi Marco , Santos Fernando P. , Van Lange Paul A. M. , Balliet Daniel
Published: September 2024

Direct reciprocity has been long identified as a mechanism to enhance cooperation in social dilemmas. While most research on reciprocal cooperation has focused on symmetrical interactions, real world interactions often involve differences in power. Verbal theories have either claimed that power differences enhance or destabilize cooperation, indicating the need for a comprehensive theoretical model of how power asymmetries affect direct reciprocity. Here, we investigate the relationship between power and cooperation in two frequently studied social dilemmas, the prisoner’s dilemma (PD) and the snowdrift game (SD). Combining evolutionary game theory and agent-based models, we demonstrate that power asymmetries are detrimental to the evolution of cooperation. Strategies that are contingent on power within an interaction provide a selective advantage in the iterated SD, but not in the iterated PD. In both games, the rate of cooperation declines as power asymmetry increases, indicating that a more egalitarian distribution of the benefits of cooperation is the prerequisite for reciprocal cooperation to evolve and be maintained.
Incompatibility groups ofPseudomonasplasmids revisited: comprehensive analysis of R-factors and their replicons
Authors: Nishimura Yosuke , Kaneko Kensei , Kamijo Tatsuya , Isogai Nanako , Tokuda Maho , Xie Hui , Tsuda Yusuke , Hirabayashi Aki , Moriuchi Ryota , Dohra Hideo , Kimbara Kazuhide , Suzuki-Minakuchi Chiho , Nojiri Hideaki , Suzuki Haruo , Suzuki Masato , Shintani Masaki
Published: September 2024

Bacterial plasmid incompatibility (Inc) groups, IncP-1 to IncP-14, have long been recognised as R-factors. These factors harbour antimicrobial resistance genes (ARGs) inPseudomonasspecies (PIncs). Despite their importance, some PIncs plasmid remain underexplored at the sequence level. This study attempts to address this gap by determining the complete nucleotide sequences of several key plasmids. Using BLAST search and AlphaFold3-based protein structure prediction, we identified replication initiation proteins (RIPs) and origins of vegetative replication (oriV) for these plasmids. Notably, mini-plasmids containing these RIP andoriVsequences successfully replicated inPseudomonas aeruginosa. Through pangenome analyses using the PLSDB database with the experimentally identified RIP gene reference, 2,351/59,895 plasmids were classified, and their core and accessory genes, including ARGs, were detected. Furthermore, phylogenetic analyses of the RIPs with publicly available protein sequences enabled the grouping of existing PIncs into distinct evolutionary lineages, providing a robust framework for identifying RIPs across a broader range of previously uncharacterised plasmids. The RIPs of 8,860 plasmids in the PLSDB were newly assigned. These findings offer crucial insights into the complex landscape of plasmid-mediated ARG dissemination, marking a significant advancement in the understanding ofPseudomonasplasmids across clinical and environmental contexts.
Gene Age Gap Estimate (GAGE) for major depressive disorder: a penalized biological age model using gene expression
Authors: Li Yijie (Jamie) , Kuplicki Rayus , Ford Bart N. , Kresock Elizabeth , Figueroa-Hall Leandra , Savitz Jonathan , McKinney Brett A.
Published: September 2024

Recent associations between Major Depressive Disorder (MDD) and measures of premature aging suggest accelerated biological aging as a potential biomarker for MDD susceptibility or MDD as a risk factor for age-related diseases. Residuals or “gaps” between the predicted biological age and chronological age have been used for statistical inference, such as testing whether an increased age gap is associated with a given disease state. Recently, a gene expression-based model of biological age showed a higher age gap for individuals with MDD compared to healthy controls (HC). In the current study, we propose an approach that simplifies gene selection using a least absolute shrinkage and selection operator (LASSO) penalty to construct an expression-based Gene Age Gap Estimate (GAGE) model. We train a LASSO gene age model on an RNA-Seq study of 78 unmedicated individuals with MDD and 79 HC, resulting in a model with 21 genes. The L-GAGE shows higher biological aging in MDD participants than HC, but the elevation is not statistically significant. However, when we dichotomize chronological age, the interaction between MDD status and age has a significant association with L-GAGE. This effect remains statistically significant even after adjusting for chronological age and sex. Using the 21 age genes, we find a statistically significant elevated biological age in MDD in an independent microarray gene expression dataset. We find functional enrichment of infectious disease and SARS-COV pathways using a broader feature selection of age related genes.
Inner membrane protein OutB is covalently attached to peptidoglycan in the γ-proteobacteriumDickeya dadantii
Authors: Nicolai Xavier , Liang Yucheng , Ruaudel Florence , Narajczyk Magdalena , Czajkowski Robert , Rusconi Filippo , Arthur Michel , Shevchik Vladimir E.
Published: September 2024

Gram-negative bacteria possess a multilayered envelope comprising an inner membrane (IM), a thin peptidoglycan (PG) layer, and an outer membrane (OM). InEscherichia coliand certain other γ-proteobacteria, Braun lipoprotein (Lpp) covalently tethers the OM to PG. Only a few other OM proteins have been found to be covalently linked to PG in Gram-negative bacteria. Here, we showed that in the phytopathogenic γ-proteobacteriumDickeya dadantii, an IM protein, OutB, is covalently attached to PG, thereby tethering itself and the associated type 2 secretion system to the cell wall. In contrast to Lpp, OutB reaches the PG layer from the IM side. By modifying the length of Lpp, which would displace the PG layer in the periplasm, we found that the elongated Lpp+21 improved OutB attachment to PG, whereas the shortened LppΔ21 reduced it. We showed that two L,D-transpeptidases, Ldt03 and Ldt84, tether Lpp and OutB to PG by the same catalytic mechanism involving the formation of an amide bond between their C-terminal lysine and the stem peptide. Ldt03 and Ldt84, each display substrate specificity for the type of peptide stem and preferentially cross-link Lpp to monomeric and dimeric muropeptide, respectively. The C-terminal Lpp-like box of OutB is almost identical to that of Lpp; it tolerates substantial amino acid substitutions and allows PG-tethering of abona fideperiplasmic protein. Thus, it seems possible that the repertoire of periplasmic and membrane proteins tethered to PG may be more extensive than currently assumed.
Overcoming nucleotide bias in the nonenzymatic copying of RNA templates
Authors: Duzdevich Daniel , Carr Christopher E. , Colville Benjamin , Aitken Harry R.M. , Szostak Jack W.
Published: September 2024

The RNA World hypothesis posits that RNA was the molecule of both heredity and function during the emergence of life. This hypothesis implies that RNA templates can be copied, and ultimately replicated, without the catalytic aid of evolved enzymes. A major problem with nonenzymatic templated polymerization has been the very poor copying of sequences containing rA and rU. Here we overcome that problem by using a prebiotically plausible mixture of RNA mononucleotides and random-sequence oligonucleotides, all activated by methyl isocyanide chemistry, that direct the uniform copying of arbitrary-sequence templates, including those harboring rA and rU. We further show that the use of this mixture in copying reactions suppresses copying errors while also generating a more uniform distribution of mismatches than observed for simpler systems. We find that oligonucleotide competition for template binding sites, oligonucleotide ligation, and the template binding properties of reactant intermediates work together to reduce product sequence bias and errors. Finally, we show that iterative cycling of the activation chemistry and templated polymerization improves the yield of random-sequence products. These results for random-sequence template copying are a significant advance in the pursuit of nonenzymatic RNA replication.
IgSeqR: a protocol for the identification, assembly, and characterization of full-length tumor Immunoglobulin transcripts from unselected RNA sequencing data
Authors: Bryant Dean , Sale Benjamin , Chiodin Giorgia , Tatterton Dylan , Stevens Benjamin , Adlaon Alyssa , Snook Erin , Batchelor James , Orfao Alberto , Forconi Francesco
Published: September 2024

Immunoglobulin (IG) gene analysis provides fundamental insight into B-cell receptor structure and function. In B-cell tumors, it can inform the cell of origin and clinical outcomes. Its clinical value has been established in the two types of chronic lymphocytic leukemia with unmutated or mutatedIGHVgenes and is emerging in other B-cell tumors. The traditional PCR-based techniques, which are labor-intensive, rely on the attainment of either a dominant sequence or a small number of subclonal sequences and do not allow automated matching with the clonal phenotypic features. Extraction of the expressed tumor IG transcripts using high-throughput RNA sequencing (RNA-seq) can be faster and allow the collection of multiple sequences matched with the transcriptome profile. Analytical tools are regularly sought to increase the accuracy, depth, and speed of acquisition of the fullIGV-(IGD)-IGJ-IGCsequences and combine theIGcharacteristics with other RNA-seq data. We provide here a user-friendly protocol for the rapid extraction, identification, and accurate determination of the full (leader to constant region) tumorIGtemplated and non-templated transcript sequence from RNA-seq. The derived amino acid sequences can be interrogated for their physico-chemical characteristics and, in certain lymphomas, predict tumor glycan types occupying acquired N-glycosylation sites. These features will then be available for association studies with the tumor transcriptome. The resulting information can also help refine diagnosis, prognosis, and potential therapeutic targeting in the most common lymphomas.
ThePseudomonas aeruginosa sphBCgenes are important for growth in the presence of sphingosine by promoting sphingosine metabolism
Authors: DiGianivittorio Pauline , Hinkel Lauren A. , Mackinder Jacob R. , Schutz Kristin , Klein Eric A. , Wargo Matthew J.
Published: September 2024

Sphingoid bases, including sphingosine, are important components of the antimicrobial barrier at epithelial surfaces where they can cause growth inhibition and killing of susceptible bacteria.Pseudomonas aeruginosais a common opportunistic pathogen that is less susceptible to sphingosine than many Gram-negative bacteria. Here, we determined that deletion of thesphBCDoperon reduced growth in the presence of sphingosine. Using deletion mutants, complementation, and growth assays inP. aeruginosaPAO1, we determined that thesphCandsphBgenes, encoding a periplasmic oxidase and periplasmic cytochrome c, respectively, were important for growth on sphingosine, whilesphDwas dispensable under these conditions. Deletion ofsphBCDinP. aeruginosaPA14,P. protegensPf-5, andP. fluorescensPf01 also showed reduced growth in the presence of sphingosine. TheP. aeruginosa sphBCgenes were also important for growth in the presence of two other sphingoid bases, phytosphingosine and sphinganine. In wild-typeP. aeruginosa, sphingosine is metabolized to an unknown non-inhibitory product, as sphingosine concentrations drop in the culture. However, in the absence ofsphBC, sphingosine accumulates, pointing to SphC and SphB as having a role in sphingosine metabolism. Finally, metabolism of sphingosine by wild-typeP. aeruginosaprotected susceptible cells from full growth inhibition by sphingosine, pointing to a role for sphingosine metabolism as a public good. This work shows that metabolism of sphingosine byP. aeruginosapresents a novel pathway by which bacteria can alter host-derived sphingolipids, but it remains an open question whether SphB and SphC act directly on sphingosine.
Matrix sketching framework for linear mixed models in association studies
Authors: Burch Myson , Bose Aritra , Dexter Gregory , Parida Laxmi , Drineas Petros
Published: September 2024

Linear mixed models (LMMs) have been widely used in genome-wide association studies to control for population stratification and cryptic relatedness. However, estimating LMM parameters is computationally expensive, necessitating large-scale matrix operations to build the genetic relationship matrix (GRM). Over the past 25 years, Randomized Linear Algebra has provided alternative approaches to such matrix operations by leveragingmatrix sketching, which often results in provably accurate fast and efficient approximations. We leverage matrix sketching to develop a fast and efficient LMM method calledMatrix-Sketching LMM (MaSk-LMM) by sketching the genotype matrix to reduce its dimensions and speed up computations. Our framework comes with both theoretical guarantees and a strong empirical performance compared to the current state-of-the-art for simulated traits and complex diseases.
Structure of the deuteron from an analysis of bremsstrahlung emission in proton-deuteron scattering in cluster models
Authors: Shaulskyi K. A. , Maydanyuk S. P. , Vasilevsky V. S.
Published: September 2024

Emission of bremsstrahlung photons in the scattering of protons off deuterons is investigated on the microscopic cluster basis in a wide region of beam energy from low energies up to 1.5 GeV.

Our aim is to construct a model extracting new information about the structure of the deuteron from analysis of accompanying bremsstrahlung in proton-deuteron scattering.

A three-cluster model of bremsstrahlung is constructed. The formalism includes the form factor of the deuteron, which characterizes the dependence of bremsstrahlung cross sections on the structure of the deuteron. This gives a possibility to investigate the structure of nuclei from analysis of bremsstrahlung cross sections.

We studied the dependence of the bremsstrahlung cross section on the structure of the deuteron. We used three different shapes of the deuteron wave functions. Besides, we also calculated the cross section by neglecting the internal structure of the deuteron. Analysis of the dependence of the cross section on such a parameter shows the following. (1) At beam energies 145 and 195 MeV used in experiments, the bremsstrahlung cross section is not sensitive enough to variations in the shape of the deuteron wave functions. (2) A stable difference between cross sections calculated with and without the internal structure of the deuteron is observed at higher bean energy (higher than 500 MeV). (3) The spectrum is increased as we pass from the structureless deuteron (the oscillator length b=0) to the deuteron described by the shell-model wave function (the realistic oscillator length) inside the full energy region of the emitted photons.

Our cluster model is a suitable tool to study the structure of the deuteron with high enough precision from bremsstrahlung analysis. We propose new experiments for such an investigation.

Published by the American Physical Society2024
Phase of the electromagnetic form factor of the pion
Authors: Ruiz Arriola Enrique , Sanchez-Puertas Pablo
Published: September 2024

We employ a dispersion relation that allows us to recover the phase of the electromagnetic form factor of the pion from its absolute value above threshold. Compared to alternative approaches building on the phase, this approach builds on experimental input directly accessible at colliders. Employing the precise datasets from the e+e−→π+π− reaction, we obtain the phase of the electromagnetic form factor up to 2.5 GeV, well beyond standard dispersive approaches. In addition, we separate the isovector and isoscalar components, that allows us to extract the P-wave ππ phase shift. We also provide relevant results, including the radius of the form factor and bounds in the spacelike region. Last, but not least, the study assess potential systematic uncertainties from the interpolation method and potential zeros of the form factor.

Published by the American Physical Society
2024
Experimental and theoretical structural investigation of an ionic Nd coordination polymer
Authors: Calisto Victoria F. M. , De Abreu Heitor A. , Diniz Renata
Published: September 2024

Research concerning coordination polymers has been intense due to their significant variability and structural stability. With this in mind, an ionic neodymium coordination polymer was synthesized, composed of an anionic one-dimensional polymer interconnected to a cationic three-dimensional porous polymer, poly[dodecaaquabis(μ-pyridine-4-carbohydrazide-κ2
N:O)bis(μ2-4-sulfobenzoato-κ2
O:O′)bis(μ3-4-sulfobenzoato-κ3
O:O′:O′′)trineodymium(III)] catena-poly[aquabis(μ-pyridine-4-carbohydrazide-κ2
N:O)bis(μ2-4-sulfobenzoato-κ2
O:O′)neodymium(III)] 4.33-hydrate, {[Nd3(C7H4O5S)4(C6H7N3O)2(H2O)12][Nd(C7H4O5S)2(C6H7N3O)2(H2O)]·4.33H2O}
n
. The ligands used were 4-sulfobenzoate (PSB) and pyridine-4-carbohydrazide, popularly known as isoniazid (INH), an antibiotic drug. The compound crystallizes in the monoclinic space group C2/c, with Z = 4. Solid-state calculations suggest that the crystal structure is mainly stabilized by hydrogen bonds, i.e. O—H...O and N—H...O interactions among the polymers, and by van der Waals interactions involving the organic side chains. This net is tetragonal, 2-nodal 3,4-connected, and can be described as the dmd (sqc 528) type.