bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogen-encoded Rum DNA polymerase drives rapid bacterial drug resistance
Authors: Jaszczur Malgorzata M , Pham Phuong , Ojha Debika , Pham Cecilia Q , McDonald John P , Woodgate Roger , Goodman Myron F
Published: October 2024

The acquisition of multidrug resistance by pathogenic bacteria is a potentially incipient pandemic. Horizontal transfer of DNA from mobile integrative conjugative elements (ICEs) provides an important way to introduce genes that confer antibiotic (Ab)-resistance in recipient cells. Sizable numbers of SXT/R391 ICEs encode a hypermutagenic Rum DNA polymerase (Rum pol), which has significant homology with Escherichia coli pol V. Here, we show that even under tight transcriptional and post-transcriptional regulation imposed by host bacteria and the R391 ICE itself, Rum pol rapidly accelerates development of multidrug resistance (CIPR, RifR, AmpR) in E. coli in response to SOS-inducing Ab and non-Ab external stressors bleomycin (BLM), ciprofloxacin (CIP) and UV radiation. The impact of Rum pol on the rate of acquisition of drug resistance appears to surpass potential contributions from other cellular processes. We have shown that RecA protein plays a central role in controlling the ability of Rum pol to accelerate antibiotic resistance. A single amino acid substitution in RecA, M197D, acts as a ‘Master Regulator’ that effectively eliminates the Rum pol-induced Ab resistance. We suggest that Rum pol should be considered as one of the major factors driving development of de novo Ab resistance in pathogens carrying SXT/R391 ICEs.
SNF2L suppresses nascent DNA gap formation to promote DNA synthesis
Authors: Nelligan Anthony , Dungrawala Huzefa
Published: October 2024

Nucleosome remodelers at replication forks function in the assembly and maturation of chromatin post DNA synthesis. The ISWI chromatin remodeler SNF2L (or SMARCA1) travels with replication forks but its contribution to DNA replication remains largely unknown. We find that fork elongation is curtailed when SNF2L is absent. SNF2L deficiency elevates replication stress and causes fork collapse due to remodeling activities by fork reversal enzymes. Mechanistically, SNF2L regulates nucleosome assembly to suppress post-replicative ssDNA gap accumulation. Gap induction is not dependent on fork remodeling and PRIMPOL. Instead, gap synthesis is driven by MRE11 and EXO1 indicating susceptibility of nascent DNA to nucleolytic cleavage and resection when SNF2L is removed. Additionally, nucleosome remodeling by SNF2L protects nascent chromatin from MNase digestion and gap induction highlighting a critical role of SNF2L in chromatin assembly post DNA synthesis to maintain unperturbed replication.
The development of polymers and fibers: an interview with Stephen Cheng
Authors: Yan Wei
Published: October 2024

Polymer and fiber science has evolved significantly since the 1920s, with polymers becoming integral to both industry and daily life. China's fiber research, initiated in the 1950s, has made substantial societal and technological contributions, particularly in chemical fibers. How will future advancements in polymers and fibers address ongoing challenges and drive further innovation?

NSR spoke to Prof. Stephen Cheng, a member of the National Academy of Engineering (U.S.) and former Dean of the College of Polymer Science and Polymer Engineering at the University of Akron. He is currently Dean and Honorable Professor at South China University of Technology. His research interests center on the condensed states in polymers, liquid crystals, surfactants and hybrid materials, focusing on the interactions, responses, dynamics and structures of materials at varying lengths, energy and timescales, in which the material itself embodies the technology.
Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children
Authors: Sherman Jacob D , Karmali Vinit , Kumar Bhoj , Simon Trevor W , Bechnak Sarah , Panjwani Anusha , Ciric Caroline R , Wang Dongli , Huerta Christopher , Johnson Brandi , Anderson Evan J , Rouphael Nadine , Collins Matthew H , Rostad Christina A , Azadi Parastoo , Scherer Erin M
Published: October 2024

Background

Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.

Methods

We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay.

Results

Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.

Conclusions

We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.
Beyond tracking: Advancing animal ecology through the longitudinal sampling of individuals
Authors: Dossman Bryant C , Filiberti Emily , Roth Amber M , Marra Peter P
Published: October 2024

Rarely, is there an opportunity to study and directly observe the same migratory animal across both breeding and nonbreeding seasons. In a rare, documented case, we highlight a live reencounter of a female Setophaga ruticilla (American Redstart) on its nest during the breeding season—an individual that was originally captured and tagged on its nonbreeding territory in Jamaica more than 3,250 km away. Advances in tracking technology allow researchers to track the movements of smaller organisms at higher resolutions. While tracking data alone have provided critical advances in the ecology of migratory animals, especially small migratory birds, there are exciting opportunities to move beyond tracking and to deeply explore biological questions about migratory animals by locating and directly studying (e.g., direct observation and physical sampling) the same individuals across the year. Although we have had the ability to precisely track large-bodied migratory birds (>100 g) for decades, researchers have rarely used these data to localize and directly observe or sample them across the year. Ultimately, we must consider the potential advances to be made in avian ecology through this endeavor. To this end, we highlight several specific areas of research that we believe move beyond tracking and can only be addressed by integrating direct longitudinal studies of individuals.
Dupilumab for refractory chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis
Authors: Padoan Roberto , Davanzo Federica , Iorio Luca , Saccardo Tommaso , Roccuzzo Giuseppe , Zampollo Sonny , Nicolai Piero , Doria Andrea , Ottaviano Giancarlo
Published: October 2024

Objectives

Eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with refractory chronic rhinosinusitis with nasal polyps (CRSwNP), despite current treatments. Dupilumab demonstrated efficacy in the treatment of severe and uncontrolled CRSwNP, with improvements in patient-reported outcome measures (PROMs) and in objective measurements. This study aims to evaluate efficacy and safety of dupilumab in refractory CRSwNP in EGPA patients.

Methods

A prospective observational study was conducted on EGPA patients treated with dupilumab between 2021 and 2023. Patients in a phase of prolonged remission of vasculitis manifestations but still experiencing active CRSwNP were included. Clinical, biological, and rhinologic evaluations were performed, alongside with PROMs and nasal cytology. Complete response was defined by BVAS = 0 and prednisone dose ≤4 mg/day, while partial response by BVAS = 0 and prednisone dose >4 mg/day.

Results

Nine EGPA patients were included. After 3 months, 55.6% achieved complete response, increasing to 83.3% at 12 months. Nasal symptoms and patient-reported outcomes improved significantly, with sustained efficacy over 12 months. An improvement in quality of life was also observed, with a significant reduction in the AAV-PRO score. Nasal cytology revealed reductions in eosinophils and neutrophils counts. Adverse events occurred in 44.4%, including hypereosinophilia in two cases, which led to dupilumab discontinuation.

Conclusion

Dupilumab is an effective treatment option for severe and refractory ENT manifestations in EGPA, as it improves symptoms, reduces inflammation, and leads to better a quality of life. However, careful patient selection and monitoring are necessary to minimize adverse events and optimize outcomes.
Unique transcriptomic profile of peripheral blood monocytes in rheumatoid arthritis-associated interstitial lung disease
Authors: Poole Jill A , Schwab Aaron , Thiele Geoffrey M , England Bryant R , Nelson Amy J , Gleason Angela , Duryee Michael J , Bailey Kristina L , Romberger Debra J , Hershberger Daniel , Van De Graaff Joel , May Sara M , Walenz Rhonda , Kramer Bridget , Mikuls Ted R
Published: October 2024

Objectives

Though interstitial lung disease (ILD) contributes to excess morbidity and mortality in rheumatoid arthritis (RA), RA-ILD pathogenesis remains incompletely defined. As intermediate, non-classical and suppressed CD14+ monocytes are expanded in RA-ILD, this study sought to characterize gene expression profiles of circulating monocytes in RA-ILD.

Methods

Peripheral blood mononuclear cells were collected from patients with RA without lung disease (n = 5), RA-ILD (n = 5), idiopathic pulmonary fibrosis (IPF; n = 5), and controls without lung and autoimmune disease (n = 4). RNA was extracted from CD14+ isolated monocytes and subjected to transcriptional analysis of 1365 genes. Gene enrichment and pathway analyses were performed.

Results

Unsupervised clustering grouped patients with RA-ILD together with IPF for myeloid innate genes. For fibrosis genes, patients with RA-ILD clustered independent of comparator groups. There were 103, 66 and 64 upregulated and 66, 14 and 25 downregulated genes for RA-ILD, RA, and IPF, vs controls, respectively. For RA-ILD, there was increased expression of genes involved in regulating inflammation and fibrosis (SOCS3, CECAM1, LTB4R2, CLEC7A, IRF7, PHYKPL, GBP5, RAPGEF), epigenetic modification (KDM5D, KMT2D, OGT) and macrophage activation. Top canonical pathways included macrophage differentiation-activation, IL-12, neuroinflammatory, glucocorticoid receptor and IL-27 signalling.

Conclusions

Circulating monocytes in RA-ILD patients demonstrate unique gene expression profiles, with innate immune gene features more aligned with IPF as opposed to RA in the absence of clinical lung disease, and with fibrosis gene expression that was distinct from RA and IPF. These studies are important for understanding disease pathogenesis and may provide information for future therapeutic targets in RA-ILD.
N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia
Authors: Tong Jinghui , Yang Kebing , Li Wei , Wang Leilei , Yin Yi , Zhou Yanfang , Huang Junchao , Zhang Ping , Zhao Yanli , Chen Song , Fan Hongzhen , Cui Yimin , Luo Xingguang , Tan Shuping , Wang Zhiren , Feng Wei , Tian Baopeng , Li Chiang-Shan R , Hong L Elliot , Tan Yunlong
Published: October 2024

Background and Hypothesis

Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia.

Study Design

We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay.

Study Results

The FES group showed higher serum NMDAR Ab levels [(9.23 ± 4.15) ng/mL vs. (7.08 ± 2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = −0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference).

Conclusions

Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.
Introduction to the Special Issue: The Lives (and Futures) of Black Children and Youth
Authors: Brooms Derrick R , Medford Marcelle M
Published: October 2024

As social science scholarship on Black children and youth continues to expand and to explore their experiences, there remains a need to investigate how families, communities, relationships, and social institutions impact their experiences. The theme for this special issue is inspired in part by our consideration of Black children’s and youths’ present realities and their futures. The editors of this volume are interested in creating space to analyze and theorize the radical possibilities for Black children to flourish in a world that typically ignores, marginalizes, and dismisses their plights and their promise. Privileging the agency of Black youth, the articles in this special issue provide nuanced accounts of how they make sense of many aspects of their lives and futures.
Evolution of virulence in emerging epidemics: from theory to experimental evolution and back
Authors: Benhamou Wakinyan , Blanquart François , Choisy Marc , Berngruber Thomas W , Choquet Rémi , Gandon Sylvain
Published: October 2024

The experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage λ spreading in continuous cultures of Escherichia coli. This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis—including calculations of the selection gradients—and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage λ. First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical, and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases.
Percutaneous Electrical Stimulation Improves Chronic Knee Pain and Function
Authors: Heredia Ciuró Alejandro , Martín Núñez Javier , Calvache Mateo Andrés , López López Laura , Cebriá I Iranzo Maria dels Angels , Cabrera Martos Irene , Valenza Marie Carmen
Published: October 2024

Objectives:

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of percutaneous electrical stimulation in the modulation of pain and its implication in the function of patients with a painful knee condition.

Materials and Methods:

A search was conducted from database inception to September 2023 across PubMed, Web of Science, and Scopus databases. Randomized controlled trials were included. Two reviewers performed independent data extraction and methodologic quality assessment of the studies. Study quality was assessed using the physiotherapy evidence database Scale and the risk of bias was evaluated with the Cochrane Assessment tool.

Results:

Eight studies were included. A significant statistical effect was found (P < 0.001) for reducing pain and improving function after treatment. In addition, a significant statistical effects were identified for reducing pain (P = 0.009) and improving function (P < 0.001) after follow-up. The risk of bias was low.

Conclusion:

This review showed a positive effect of applying the percutaneous electrical stimulation for reducing pain and improving function in adults with a painful knee.
Penile and Scrotal Porokeratosis: A Single-Institution Experience
Authors: Tekin Burak , Gupta Sounak , Guo Ruifeng , Lehman Julia S. , Wieland Carilyn N. , Johnson Emma F.
Published: October 2024

There is a paucity of data regarding porokeratosis confined to the penis and scrotum. We evaluated our single-institutional experience regarding this entity. We interrogated our pathology archive for all specimens from the penis or scrotum, signed out as porokeratosis between 2000 and 2022. Clinical and histopathological features were reviewed, including the number of cornoid lamella(e) per tissue profile and squamous dysplasia. Nine patients were included in the study. The median age at the time of diagnosis was 51 years. Multiple lesions were present in 3 patients. Six patients had exclusively penile involvement, whereas 2 patients had exclusively scrotal involvement. One patient had multiple lesions consistent with porokeratosis ptychotropica, extending from the scrotum to the buttocks and perineum. Clinically, a collarette of scale was noted in 3 patients and diagnosis of porokeratosis was considered in 1 patient before biopsy. Histopathologically, 2 patients exhibited multiple cornoid lamellae in the same profile and 1 patient had follicular cornoid lamellae. Focal squamous dysplasia was only present in 1 patient. Follow-up was available for 5 patients (median duration: 35 months). In 4 patients, the lesions were removed completely during the shave biopsy procedure. At the past follow-up, there were no signs of recurrence or malignant transformation to squamous cell carcinoma in any patient. Porokeratosis involving the penis and/or scrotum may be elusive to diagnosis based on clinical features alone, emphasizing the role of histopathological examination. Increased awareness of this entity may help better delineate its clinicopathological presentation and appropriate classification.
Pseudolipoblastic Perineuroma: A Rare Histologi̇c Subtype
Authors: Erdem Ozlem , Corti Barbara , Paolo Salamone Francesco , Piraccini Bianca Maria , Misciali Cosimo
Published: October 2024

Pseudolipoblastic perineurioma is a very uncommon variant of extraneural perineurioma, with only a limited number of cases documented in the medical literature. The most remarkable histopathologic characteristic is the existence of vacuolated cells that closely resemble lipoblasts; besides the presence of small, spindle shaped, or epithelioid perineurial cells. In this study, we present another case of pseudolipoblastic perineurioma, predominantly characterized by the presence of vacuolated “pseudolipoblastic” cells. The immunohistochemical expression of EMA, Glut-1, claudin-1, collagen type IV, and laminin as well as S-100 negativity is essential for the diagnosis to support the perineurial origin. Simple excision is the best treatment option for these benign tumors that do not recur or metastasize. It is crucial to recognize this rare entity to differentiate it from many other tumors characterized by prominent intracytoplasmic vacuoles.
Inter-rater Reliability of Pressure Pain Threshold Between Experienced and Novice Examiners: A Case Study of 2 Educational Approaches
Authors: Wilson Abigail T. , Rothschild Carey E.
Published: October 2024

Background and Purpose.

Pressure Pain Threshold (PPT) is used to objectively assess pain in clinical settings and is a recommended part of physical therapist education. An individual who is experienced in administering PPT will frequently train a student on the technique; however, optimal educational approaches for this instruction have not yet been identified. Therefore, the purpose of this case report is to describe 2 educational approaches (unstructured lecture and structured feedback with clinical relevance) in training 2 separate cohorts of Doctor of Physical Therapy students in PPT. The primary outcome of interest was the inter-rater reliability of PPT between an experienced and novice examiner.

Case Description.

Cohort 1 (n = 37) received a traditional lecture approach consisting of watching a prerecorded video online, an in-person lecture with demonstration of the technique, and time to practice. Cohort 2 (n = 34) received the prerecorded video online and lecture with demonstration; however, key additions included a clinical relevance discussion along with structured peer-to-peer and instructor-to-student feedback using a competency-based checklist. PPT was assessed by each student (novice examiner) and one instructor (experienced examiner). Inter-rater reliability of PPT between a novice and experienced examiner was evaluated.

Outcomes.

Inter-rater reliability improved from poor/moderate (intraclass correlation coefficient low back = 0.46 [0.16–0.68], quadriceps = 0.54 [0.26–0.73]) to good (low back = 0.84 [0.67–0.92], quadriceps = 0.90 [0.79–0.95]) after the addition of structured feedback.

Discussion.

Structured feedback from peers and instructors may be useful when learning PPT and improving inter-rater reliability, which has implications for training students within a laboratory or classroom. However, this case study would need to be replicated in an experimental design to examine the effects of varying types of feedback on learning outcomes.
Does the introduction of the acuity circle policy change split liver transplantation practice?
Authors: Nakayama Toshihiro , Akabane Miho , Imaoka Yuki , Esquivel Carlos O. , Melcher Marc L. , Sasaki Kazunari
Published: October 2024

With the acuity circles (AC) policy aiming to reduce disparities in liver transplantation (LT) access, the allocation of high-quality grafts has shifted, potentially affecting the use and outcomes of split LT. Data from the United Network for Organ Sharing (UNOS) database (February 4, 2016, to February 3, 2024) were analyzed, including 1470 candidates who underwent deceased donor split LT, with 681 adult and 789 pediatric cases. The study periods were divided into pre-AC (February 4, 2016, to February 3, 2020) and post-AC (February 4, 2020, to February 3, 2024). The study assessed changes in split LT volumes and examined the impact of center practices. Both adult and pediatric split LTs decreased in the initial 3 years after the policy change, followed by an increase in the final year, with an overall 11.9% and 13.9% decrease between the eras. Adult female split LT cases remained consistent, ensuring access for smaller recipients. High-quality “splittable” livers were increasingly allocated to high MELD patients (MELD-Na ≥30). Despite the overall decrease in case volume, adult split LT volume increased in newly active living donor liver transplantation centers, with 6 centers increasing living donor liver transplantation volume by over 50.0%. Pediatric split LT volumes decreased despite additional priorities for pediatric candidates. The number of split LTs decreased in the initial period after the AC policy introduction, but there was a consistent need for small female candidates. In the adult population, living donor liver transplantation and split LT demonstrated a synergistic effect in boosting center transplant volumes, potentially improving access for female candidates who need small grafts.
Household air pollution and respiratory health in Africa: persistent risk and unchanged health burdens
Authors: Jafta Nkosana , Shezi Busisiwe , Buthelezi Minenhle , Muteti-Fana Shamiso , Naidoo Rajen N.
Published: October 2024

Purpose of review

Despite evidence emerging from the Global Burden of Disease studies that biomass use and household air pollution are declining globally, with important positive health impacts for households in low- and middle-income countries, these trends have not been equally documented in African countries. This review describes the state of household air pollution exposure and its relationship with respiratory disease in Africa.

Recent findings

African studies on this topic are limited, and generally focus on respiratory infections. Most evidence emerge from models based on the Global Burden of Disease data, and from limited individual epidemiological studies across the continent. More than 80% of the African population is exposed to household air pollution. Women and children continue to bear the substantial burden of exposure. Evidence from limited exposure-response studies strongly points to household air pollution being the major driver of acute and chronic respiratory diseases on the continent.

Respiratory infections, particularly in children, and other chronic respiratory diseases, are strongly attributable to household air pollution. Elimination of such exposures through interventions such as cleaner fuels and preferably, electricity, is critical to improving respiratory health on the continent.
Update on the immunological mechanisms of primary graft dysfunction and chronic lung allograft dysfunction
Authors: Jeong Jong Cheol , Gelman Andrew E. , Chong Anita S.
Published: October 2024

Purpose of review

Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD.

Recent findings

Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8+ T cells, classical monocytes, and eosinophils.

Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment.
Characterizing the Patterns of Cervical Cancer Symptom Recognition, Symptom Response, and Associated Factors Among Patients Treated in a Teaching Hospital in Ghana
Authors: Oppong Anita Frimpomaa , Nwozichi Chinomso Ugochukwu , Boakye Emelia Osei , Kyei Evans Frimpong
Published: October 2024

Background

Cervical cancer is a major global health issue and ranks as the second leading cause of cancer-related deaths among women in Ghana.

Objective

This study aimed to explore and characterize the patterns of symptom recognition associated with cervical cancer and the symptom responses among women in Ghana.

Methods

A descriptive qualitative design utilizing 20 individual semistructured interview sessions was used. The study was conducted in one of Ghana’s major cancer treatment centers. Data were collected using face-to-face interviews. The data were analyzed using NVivo 12 and presented as themes and subthemes.

Results

Data analysis revealed 2 main themes: barriers to symptom recognition and response and facilitators of early symptom recognition and symptom response. Barriers included deficient knowledge about cervical symptoms, spiritual attributions of symptoms, preference for herbal remedies for symptoms, misdiagnosis, and seeking help through multiple facility visits. Facilitating factors of symptom response include perceived severity/identification of additional symptoms, quick referrals with some navigation within the healthcare system, and advice from women’s microcommunity.

Conclusion

The study emphasizes the need for continuous educational efforts on cervical cancer and its symptoms. Healthcare providers, patients, and the public have a part to play in the awareness and early detection of cervical cancer. Initiatives that educate women about the early symptoms of cervical cancer and the importance of screening can help with early recognition.

Implication for Practice

Educating communities about cervical cancer empowers individuals to take charge of their health and encourages supportive environments for women to seek care.
Vascular Resection for Pancreas Cancer – 10-year Experience from a Single High Volume-center
Authors: Henault David , Kunde Holden , Zatzman Cody , Bevacqua Daniela , Arshinoff Danielle LA. , Cleary Sean P. , Dawson Laura A. , Elimova Elena , Grant Robert , Hosni Ali , Jang Raymond W. , Knox Jennifer J. , Mesci Aruz , Moore Malcolm , Moulton Carol-Anne E. , Reichman Trevor W. , Shwaartz Chaya , Tsang Erica S. , McGilvray Ian D. , Gallinger Steven
Published: October 2024

Objective & Background:

Combined pancreatic and vascular resections are increasingly performed for pancreatic ductal adenocarcinoma (PDAC). We evaluated the outcomes after pancreatectomy with non-vascular resection (NVR), venous resection (VR), and arterial resection (AR).

Methods:

Retrospective review (2011–2023) of 715 PDAC patients treated with curative-intent surgery. Associations among clinicopathological data, perioperative therapy, time to recurrence (TTR), and overall survival (OS) were evaluated.

Results:

Initial staging revealed 533 resectable, 98 borderline, and 84 locally advanced PDAC cases. Pancreaticoduodenectomy was the most common procedure (n=467). NVR was performed in 351 (58.2%) patients, VR in 181 (30.0%), and AR in 70 (11.8%). The median TTR and OS did not significantly differ according to the initial staging or type of pancreas resection. Median TTR and OS were significantly shorter for VR (14.5 and 22.7 mo) compared to NVR (18.6 and 30.5 mo, P<0.001) and AR (20.6 and 30.9 mo, P=0.004 and P=0.017). Chemotherapy or chemoradiation significantly prolonged TTR (20.1 vs. 10.2 mo, P<0.001 and 25.3 vs. 16.4 mo, P<0.001) and OS (31.5 vs. 17.2 mo, P<0.001 and 35.5 vs. 27.5 mo, P=0.030). AR was associated with higher 90-day mortality rates. In the multivariable analysis, vascular resection was not associated with OS. Perioperative therapy, pathological N0 status, and absence of perineural invasion were the key predictors of longer TTR and OS.

Conclusions:

Pancreatectomy with AR was not associated with worse oncological outcomes when controlling for perioperative therapy. However, AR was associated with higher 90-day mortality rates. Patient selection is crucial when performing AR in patients with PDAC.
Efficacy of Intraoperative vs Preoperative Indocyanine Green Administration for Near-Infrared Cholangiography During Laparoscopic Cholecystectomy: An Open-Label, Noninferiority, Randomized Controlled Trial
Authors: Lin Wenjun , Tao Haisu , Zeng Xiaojun , Wang Junfeng , Zhu Wen , Zeng Ning , Xiang Nan , Liu Jun , Fang Chihua , Yang Jian
Published: October 2024

BACKGROUND:

Near-infrared fluorescence cholangiography improves the clinical effects of laparoscopic cholecystectomy. However, the administration of indocyanine green remains controversial. Both the intraoperative strategy (IS, 0.05 mg) and preoperative strategy (PS, 0.25 mg/kg body weight, 1 day before operation) have been shown to be superior to the standard strategy (2.5 mg, intraoperative). This trial was designed to determine whether IS offers noninferior visualization of biliary ducts compared with PS.

STUDY DESIGN:

A total of 168 eligible patients undergoing laparoscopic cholecystectomy were enrolled in this noninferiority, open-label, randomized controlled trial at Zhujiang hospital between August 2023 and November 2023. Participants were randomized in a 1:1 ratio into PS and IS groups after stratification by BMI and inflammation level. The fluorescence visualization of biliary structures was assessed by comparing the signal-to-background ratio (SBR) and surgeon evaluations.

RESULTS:

The common bile duct-liver SBR did not significantly differ between IS and PS groups (3.0 ± 0.8 vs 3.1 ± 1.2; p = 0.636). The liver fluorescence intensity of the IS group was significantly lower than that of the PS group (46.3 ± 12.9 vs 70.4 ± 26.2; p < 0.01). The visualization score of common hepatic ducts was significantly greater in the IS than in the PS group (4.1 ± 0.7 vs 3.7 ± 0.6; p< 0.01). The critical view of safety was achieved more rapidly in the IS group compared with the PS group (9.4 vs 11.0 minutes, p < 0.01).

CONCLUSIONS:

Although IS did not improve the SBR, it significantly reduced the fluorescence intensity of the liver background, potentially enhancing the surgeon’s subjective perception and thereby increasing the visualization score. Compared with PS, IS offers greater convenience and is more effective in facilitating critical view of safety exposure.
Fungi as Turing automata with oracles
Authors: Schumann Andrew , Adamatzky Andrew , Król Jerzy , Goles Eric
Published: October 2024

In the article, we aim to understand the responses of living organisms, exemplified by mycelium, to external stimuli through the lens of a Turing machine with an oracle (oTM). To facilitate our exploration, we show that a variant of an oTM is a cellular automaton with an oracle, which aptly captures the intricate behaviours observed in organisms such as fungi, shedding light on their dynamic interactions with their environment. This interaction reveals forms of reflection that can be interpreted as a minimum volume of consciousness. Thus, in our study, we interpret consciousness as a mathematical phenomenon when an arithmetic function is arbitrarily modified. We call these modifications the hybridization of behaviour. oTMs are the mathematical language of this hybridization.
Announcement of the whole genome resource of Brevibacillus formosus YSY-2.2, a chitin-degrading bacterium possessing antifungal activity and producing phytohormones
Authors: TRAN Dinh Minh , Huynh To Uyen , Nguyen Dinh Sy , Pentekhina Iuliia
Published: October 2024

This work announced the whole genome resource of Brevibacillus formosus YSY-2.2, a chitin-degrading bacterium possessing antifungal activity and producing phytohormones previously isolated from Yok Don National Park, Vietnam. The genome contained 6,191,946 bp with 47.3% GC content, 5,791 CDSs, 116 RNAs, 101 CAZymes, and 13 BGCs. It showed the highest values of both ANI (95.07%) and dDDH (72.6%) to those of B. formosus NF2 (CP018145). The genome sequence will provide useful information for further studies on the functional gene and application of B. formosus YSY-2.2.
Tn4661-mediated transfer of bla
CTX-M-15 from Klebsiella michiganensis to an outbreak clone of Pseudomonas aeruginosa
Authors: Bartlett Katelyn V. , Luo Ting L. , Ong Ana C. , Maybank Rosslyn A. , Stribling William , Thompson Bernadette , Powell Aubrey , Kwak Yoon I. , Bennett Jason W. , Lebreton Francois , Mc Gann Patrick T.
Published: October 2024

Carriage of CTX-M-type extended-spectrum β-lactamase (ESBL) is rare in Pseudomonas aeruginosa. During routine surveillance of an endemic ST-621 P. aeruginosa at a large hospital, isolate MRSN 100690 carrying bla
CTX-M-15 was cultured from a patient (P2). This was the first detection of this ESBL in the endemic ST-621 lineage. All 1 488 bacterial isolates collected from the same facility in the 12 months prior to the incidence of 100 690 were screened for the presence of bla
CTX-M-15. A set of 183 isolates was identified, in which corresponding patient metadata was evaluated for spatiotemporal overlaps with P2. The resulting three isolates, along with 100 690, were long-read sequenced using the Oxford Nanopore MinION platform to determine a potential donor of bla
CTX-M-15. The screen revealed a single Klebsiella michiganensis isolate, MRSN 895358, which carried an IncA/C2 plasmid harbouring bla
CTX-M-15. Notably, the patient harbouring 895358, P1, occupied the same hospital room as P2 9 months prior. Genomic alignment revealed that both isolates shared an identical 80.8 kb region containing the IncA/C2 plasmid replicon and bla
CTX-M-15. This region was plasmid bound in 895 358, but chromosomally bound in 100 690 due to Tn4661-mediated transposition. ESBL bla
CTX-M-15 was acquired and subsequently integrated into the chromosome of a ST-621 P. aeruginosa, likely initiated by plasmid transfer from a K. michiganensis strain.
Plasma Glial Fibrillary Acidic Protein (GFAP) as a Biomarker of Acute Focal Brain Injury
Authors: Saez-Calveras Nil , Asturias Alexander , Yu James , Stopschinski Barbara , Vaquer-Alicea Jaime , O’Suilleabhain Padraig , Diamond Marc I. , Shah Bhavya R.
Published: October 2024

Objective

The validation of acute brain injury biomarkers has encountered challenges such as the absence of pre-insult measurements, variability in injury timing and location, and interindividual differences. In this study, we addressed these limitations by using Magnetic Resonance-guided High-Intensity Focused Ultrasound (MRgHIFU) thalamotomy to assess plasma biomarker changes after an acute focal brain injury.

Methods

This prospective study included 30 essential tremor (ET) and tremor-dominant Parkinson’s disease (TDPD) patients undergoing MRgHIFU thalamotomy at a single academic institution. Blood samples were collected at three specific time points: pre-procedure, 1-hour post-procedure, and 48 hours post-procedure. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta (Aβ40 and Aβ42), and phosphorylated tau 181 (pTau-181) were measured using the Quanterix Single Molecule Arrays (SiMoA) assay.

Results

GFAP levels significantly increased 48 hours post-MRgHIFU in all patients with a thalamotomy lesion. GFAP levels were highly sensitive (89.7%) and specific (96.6%) in detecting the presence of a HIFU lesion with a cutoff value of 216.2 pg/ml. NfL, Aβ40, and Aβ42, also showed statistically significant increases post-procedure but were less robust than GFAP. No changes were observed in pTau-181 levels post-MRgHIFU.

Conclusion

Plasma GFAP emerged as a highly sensitive and reliable biomarker for detecting acute brain injury following MRgHIFU thalamotomy. The significant post-procedure elevation of GFAP suggests its potential as an early diagnostic tool for focal brain injuries, particularly in acute stroke. Further research is needed to validate the GFAP injury cutoff identified in this study and to explore its broader clinical utility in the early detection of focal brain lesions.
A prospective study of pre-operative risk factors associated with extended length of stay in patients attending a pre-operative clinic in South Africa
Authors: Naidu Kuven , Kajee Nabeela , Naidu Jayseelan , Wadee Bilaal
Published: October 2024

Background

Preoperative assessment clinics play a critical role in identifying, evaluating, and mitigating perioperative risks. Despite global data highlighting the importance of preoperative risk factors on surgical outcomes, there remains limited information on their impact on postoperative length of stay in South African contexts.

Objectives

This study aimed to describe the demographic and clinical profiles of patients referred to a preoperative clinic in Johannesburg, South Africa, and to examine factors associated with postoperative length of stay (LOS).

Methods

This was a prospective cohort study conducted between 2021 and 2022 at a private clinic. Patients aged ≥18 years undergoing non-cardiac surgery were included. Data on demographics, comorbidities, surgical procedures, and clinical outcomes were collected. Statistical analysis was performed to assess relationships between preoperative risk factors, including ASA grading, Revised Cardiac Risk Index (RCRI), eGFR, Diabetes Mellitus, age, obesity and LOS.

Results

A total of 214 patients were assessed, of which 75.7% were female, with a median age of 62.5 years. Common comorbidities included hypertension (59.3%) and obesity (55%). The median LOS was 3.5 days, with 47.2% of patients staying more than 3 days postoperatively. Knee (33.2%) and hip surgeries (21%) were the most common procedures. A significant association was found between longer LOS and RCRI score ≥1 (p=0.007), as well as renal dysfunction in knee surgery patients (p=0.027) and age in patients undergoing hip surgery (p=0.049). There was no significant association between ASA grade, presence of diabetes mellitus, eGFR, age or obesity.

Conclusions

Increased RCRI scores, renal dysfunction, and age were associated with prolonged hospital stay. Findings highlight the need for targeted interventions in preoperative care to reduce LOS, particularly for high-risk patients. Further research is needed to validate these results across broader healthcare settings and to establish appropriate protocols for South African patients undergoing pre-operative assessment.
Joint effects of sleep duration and depression on the risk of cardiovascular disease and mediating role of depression in middle-aged and older Chinese adults: a nationwide prospective cohort study
Authors: Yu Shandong , Chu Yanpeng
Published: October 2024

Background Cardiovascular diseases (CVD) are the leading cause of mortality in China. Depression and sleep disturbances are recognized as risk factors for CVD, but their interplay and combined effects remain unclear. This study examines how sleep duration and depression interact to influence CVD risk. Methods We analyzed data from five waves of the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2020. The final sample included 12,050 individuals aged 45 and above. Sleep duration was categorized as 6 hours or less, 6?8 hours and >8 hours. Depression was assessed using the CESD-10 score and categorized as no depression, mild/moderate depression, and severe depression. Cox proportional hazards models assessed the association between sleep, depression, and CVD. Mediation analysis explored depression?s role in this relationship. Results Short sleep duration was associated with a higher CVD risk (HR 1.19; 95% CI: 1.03?1.38). Restricted cubic spline (RCS) analysis showed a U-shaped association between sleep duration and CVD risk, with the lowest risk observed at 7.61 hours of sleep. Severe depression further increased CVD risk when combined with short sleep duration (HR 2.08; 95% CI: 1.46-2.95) or long sleep duration (HR 2.08; 95% CI: 1.05-5.35). Mediation analysis revealed that depression explained 43.8% of the total effect of short sleep on CVD. Conclusions Both short sleep and depression independently raise the risk of CVD, with depression partially mediating the effect of sleep on cardiovascular health. Interventions targeting both sleep and mental health could reduce CVD risk in high-risk populations.
The future abundance of key bird species for pathogen transmission in the Netherlands
Authors: Dellar Martha , Sierdsema Henk , van Bodegom Peter M. , Schrama Maarten , Geerling Gertjan
Published: October 2024

Wild birds serve as reservoirs and vectors for many different pathogens and changes in their distribution and abundance due to environmental change will influence disease risk. We study three species which are highly abundant in north-western Europe and which can transmit a wide range of diseases including avian influenza and West Nile virus: blackbirds, mallards and house sparrows. Using the Netherlands as a case study, we created random forest models for predicting the distribution and abundance of these species, both now and in the future. Climate, land use and vegetative cover were all important predictors of bird abundance. The three species had different spatial distributions, largely related to their preferred habitat and food availability. In the future, mallard and house sparrow populations were predicted to increase, while there was little change for blackbirds. Quantifying the consequences of these abundance changes is complicated as there are many factors to consider, however increased pathogen reservoirs will likely increase disease risk and changes in distribution may affect local outbreak risk. The future abundance maps created in this study, and the methods used to create them, will be useful tools for disease modellers and policymakers to estimate future disease risk and to plan accordingly.