bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural stem cell therapies for spinal cord injury repair: an update on recent preclinical and clinical advances
Authors: Hosseini Seyed Mojtaba , Borys Ben , Karimi-Abdolrezaee Soheila
Published: November 2023

Traumatic spinal cord injury (SCI) is a leading cause of lifelong disabilities. Permanent sensory, motor and autonomic impairments after SCI are substantially attributed to degeneration of spinal cord neurons and axons, and disintegration of neural network. To date, minimal regenerative treatments are available for SCI with an unmet need for new therapies to reconstruct the damaged spinal cord neuron-glia network and restore connectivity with the supraspinal pathways.

Multipotent neural precursor cells (NPCs) have a unique capacity to generate neurons, oligodendrocytes and astrocytes. Due to this capacity, NPCs have been an attractive cell source for cellular therapies for SCI. Transplantation of NPCs has been extensively tested in preclinical models of SCI in the past two decades. These studies have identified opportunities and challenges associated with NPC therapies. While NPCs have the potential to promote neuroregeneration through various mechanisms, their low long-term survival and integration within the host injured spinal cord limit the functional benefits of NPC-based therapies for SCI.

To address this challenge, combinatorial strategies have been developed to optimize the outcomes of NPC therapies by enriching SCI microenvironment through biomaterials, genetic and pharmacological therapies. In this review, we will provide an in-depth discussion on recent advances in preclinical NPC-based therapies for SCI. We will discuss modes of actions and mechanism by which engrafted NPCs contribute to the repair process and functional recovery. We will also provide an update on current clinical trials and new technologies that have facilitated preparation of medical-grade human NPCs suitable for transplantation in clinical studies.
The Numinous Presence That Binds: How the Chaplain Navigates Disparate Commitments Through the Lens of Hospital Baptism
Authors: Rebouché Madeleine
Published: November 2023

This article explores the often-disparate commitments the chaplain has made to both the institutional church as well as the hospital system through the lens of the baptismal rite. As baptism is primarily a religious act meant to initiate new members into the Christian faith and a specific community, the chaplain must grapple with the meaning of baptism in the hospital system, a place of crisis and transient community. It is the numinous presence that binds the chaplain’s disparate commitments together in the liminal space between the clinical and ecclesial within which the chaplain exists. The numinous expands the boundaries of institutions often at odds. The chaplain finds meaning and purpose by bearing witness and remaining committed to this numinous presence that binds.
Spesolimab treatment in a patient with generalized pustular psoriasis: a case report with 12-month follow-up and literature review
Authors: Cardenas-de la Garza Jesus Alberto , Zazueta-López Rosa María , Garza-Elizondo Angel Kevin , Flores-Gutierrez Diana Paola , Welsh Esperanza
Published: November 2023

This article explores the use of spesolimab in generalized pustular psoriasis (GPP) and presents the case of a Hispanic patient with GPP and plaque psoriasis treated with spesolimab and the 12-month follow-up presenting remission and significant improvement of their plaque psoriasis. A literature review identified limited cases of GPP treated with spesolimab with high response rates to the biologic and frequent mild adverse events. Most articles do not mention a previous history of plaque psoriasis and its response to spesolimab. This report highlights the efficacy of spesolimab in managing GPP, although further research is needed to assess the long-term effects of spesolimab in patients with GPP, particularly those with a history of plaque psoriasis.
Basan syndrome in a family from South India: a novel SMARCAD1 variant
Authors: Mathews Irene , Wagh Shivangi , Baby Aimin , Chandrashekar Laxmisha , Dalal Ashwin
Published: November 2023

Basan syndrome is a rare ectodermal dysplasia characterized by a triad of adermatoglyphia, reticulate pigmentation and nail dystrophy, in addition to transient neonatal findings of acral blistering and facial milia. The genetic basis was recently established to be heterozygous mutations affecting the skin-specific isoform of SMARCAD1. It is now considered part of the spectrum of disorders resulting from haploinsufficiency of this isoform, which includes both Huriez syndrome and autosomal dominant adermatoglyphia. Here, we describe a family with Basan syndrome from South India with a novel SMARCAD1 variant (c.378+1delGTAA) affecting the known mutational hotspot in exon 1.
Development of chilblain lesions during the COVID-19 pandemic is strongly associated with cold weather: a retrospective analysis of patients from a single centre in the USA
Authors: Muser Inga , Gallop Josh , Narang Jatin , Flatley Elizabeth M , Tamburro Joan , Riegert Maureen , Fernandez Anthony P
Published: November 2023

This study aimed to retrospectively investigate the association between chilblain lesions and SARS-CoV-2 infection. Our results demonstrate a stronger and more significant association between incidence of chilblain cases and monthly temperature compared with incidence of SARS-CoV-2 infection. These results suggest cold weather was an important risk factor for developing chilblains during the COVID-19 pandemic.
Immunological dynamic characteristics in acute myeloid leukemia predict the long-term outcomes and graft-versus host-disease occurrences post-transplantation
Authors: Wang Weiwei , Li Haibo , Guo Yukun , Zhang Lihua , Jiang Wenli , Zheng Naisheng , Peng Se , Guan Xiaolin , Fan Guang , Shen Lisong
Published: November 2023

To investigate the relationship between immune dynamic and graft-versus-host-disease (GVHD) risk, 111 initial diagnostic acute myeloid leukemia patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in bone marrow (BM) from 60 transplant patients at four different time points were analyzed. Additionally, 90 immune subsets in peripheral blood (PB) of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer OS compared to non-transplant patients (P < 0.001). Among transplant patients, those who developed GVHD showed longer OS than those without GVHD (P < 0.05). URD donors and CMV-negative status donors were associated with improved OS in transplant patients (P < 0.05). Importantly, we observed a decreased Th/Tc ratio in BM at initial diagnostic in patients with GVHD compared to those without GVHD (P = 0.034). Receiver operating characteristic analysis indicated that a low Th/Tc ratio predicted an increased risk of GVHD with a sensitivity of 44.44% and specificity of 87.50%. Moreover, an increased T/NK ratio in BM of post-induction chemotherapy was found to be associated with GVHD, with a sensitivity of 75.76% and specificity of 65.22%. Additionally, we observed a decreased percentage of NK1 (CD56-CD16+NK) in PB on day 100 post-transplantation in the GVHD group (P < 0.05). These three indicators exhibit promising potential as specific and useful biomarkers for predicting GVHD. These findings provide valuable insights for the early identification and management of GVHD risk, thereby facilitating the possibility of improving patient outcomes.
Simultaneous Determination of General Active Ingredients in Topical Formulations by Gas Chromatography with Flame Ionization Detection (GC-FID)
Authors: Ioutsi Anna , Sarnitskaya Anastasia , Sumtsov Mikhail
Published: November 2023

A simple, fast, precision and sensitive gas chromatographic method was developed for determination of camphor, L-menthol, methyl salicylate, salicylic acid, benzyl nicotinate and nonivamide in topical formulations. The possibility of determination low-boiling components and high-boiling components by a single analytical method was shown. The method was optimized by evaluating the effect of a large number of chromatographic parameters and sample preparation stages. It was validated according to the International Council on Harmonization guidelines. Limit of quantification of active components were achieved from 0.7 μg/mL for benzyl nicotinate and L-menthol to 41 μg/mL for salicylic acid. High repeatability and good recovery values were demonstrated. The practical application of the proposed method was shown for ointments and cream.
Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M Extended-Spectrum β-Lactamase-Producing Enterobacterales Bloodstream Infections?
Authors: Hareza Dariusz A , Cosgrove Sara E , Simner Patricia J , Harris Anthony D , Bergman Yehudit , Conzemius Rick , Jacobs Emily , Beisken Stephan , Tamma Pranita D
Published: November 2023

Background

Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Patient outcomes from non–CTX-M-producing ESBL-E BSIs and optimal treatment are unknown.

Methods

A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018–2022 was conducted. Broth microdilution and whole-genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores ensured patients with non–CTX-M and CTX-M ESBL-E BSIs were similar before outcome evaluation.

Results

396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: blaCTX-M (n = 370), blaSHV (n = 16), blaOXY (n = 12), and blaVEB (n = 5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non–CTX-M and CTX-M groups (odds ratio [OR], 0.99; 95% confidence interval [CI], .87–1.11; P = .83 and OR, 1.10; 95% CI, .85–1.42; P = .47, respectively). In an exploratory analysis limited to the non–CTX-M group, 86% of the 21 patients who received meropenem were alive on day 30; none of the 5 patients who received piperacillin-tazobactam were alive on day 30.

Conclusions

Our findings suggest that non–CTX-M and CTX-M ESBL-E BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non–CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for ESBL-E BSIs beyond just blaCTX-M genes.
Early predictors of clinical deterioration in intermediate-high risk pulmonary embolism: clinical needs, research imperatives, and pathways forward
Authors: Zuin Marco , Becattini Cecilia , Piazza Gregory
Published: November 2023

A subset of intermediate-high risk pulmonary embolism (PE) patients will suffer clinical deterioration in the early hours following the acute event. Current evidence-based guidelines for the management of acute PE have provided limited direction for identification of which intermediate-high risk PE patients will go on to develop haemodynamic decompensation. Furthermore, a paucity of data further hampers guideline recommendations regarding the optimal approach and duration of intensive monitoring, best methods to assess the early response to anticoagulation, and the ideal window for reperfusion therapy, if decompensation threatens. The aim of the present article is to identify the current unmet needs related to the early identification of intermediate-high risk PE patients at higher risk of clinical deterioration and mortality during the early hours after the acute cardiovascular event and suggest some potential strategies to further explore gaps in the literature.
Power mismatch and civil conflict: an empirical investigation
Authors: Morelli Massimo , Ogliari Laura , Hong Long
Published: November 2023

This paper empirically shows that the imbalance between an ethnic group’s political and military power is crucial to understanding the likelihood that such a group engages in a conflict. We develop a novel measure of a group’s military power by combining machine-learning techniques with rich data on ethnic group characteristics and outcomes of civil conflicts in Africa and the Middle East. We couple this measure with available indicators of an ethnic group’s political power as well as with a novel proxy based on information about the ethnicity of cabinet members. We find that groups characterized by a higher mismatch between military and political power are between 30% and 50% more likely to engage in a conflict against their government depending on the specification used. We also find that the effects of power mismatch are non-linear, which is in agreement with the predictions of a simple model that accounts for the cost of conflict. Moreover, our results suggest that high-mismatched groups are typically involved in larger and centrist conflicts. The policy implication is that power-sharing recommendations and institutional design policies for peace should consider primarily the reduction of power mismatches between relevant groups, rather than focusing exclusively on equalizing political power in isolation.
Role of ideal cardiovascular health metrics in reducing risk of incident arrhythmias
Authors: Cheng Yun-Jiu , Deng Hai , Liao Yi-Jian , Fang Xian-Hong , Liao Hong-Tao , Liu Fang-Zhou , He Qian , Wang Jin-Jie , Wu Shu-Lin , Lin Wei-Dong , Xue Yu-Mei
Published: November 2023

Aims

Cardiovascular health (CVH) has been proven to reduce cardiovascular disease burden and mortality, but data are lacking regarding cardiac arrhythmias. The aim of this study was to assess the association between CVH metrics and atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias.

Methods and results

This study analysed data from the Atherosclerosis Risk in Communities (ARIC) cohort, with participants recruited from four different communities across the United States. Cardiovascular health metrics were scored at baseline (1987–89) following the American Heart Association’s recommendations and categorized as poor, intermediate, or ideal. Arrhythmia episodes were diagnosed by International Classification of Diseases (ICD)-9 code. Adjusted associations were estimated using Cox models and event rates and population attributable fractions were calculated by CVH metrics category. The study population consisted of 13 078 participants, with 2548 AF, 1363 ventricular arrhythmias, and 706 bradyarrhythmias occurred. The adjusted hazard ratios (HRs) for ideal (vs. poor) CVH metrics were 0.59 [95% confidence interval (CI): 0.50–0.69] for AF, 0.38 (95% CI: 0.28–0.51) for ventricular arrhythmias, and 0.70 (95% CI: 0.51–0.97) for bradyarrhythmia. The risk of incident arrhythmias decreased steadily as the CVH metrics improved from 0 to 14 scores. The adjusted population attributable fractions were calculated to be 29.9% for AF, 54.4% for ventricular arrhythmias, and 21.9% for bradyarrhythmia, respectively. The association between CVH metrics and incident arrhythmias was also seen in people who remained free of coronary heart disease over the follow-up.

Conclusion

Achieving ideal CVH metrics recommendations by AHA in midlife was associated with a lower risk of incident arrhythmias later in life.
Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome
Authors: Kaizer Alexander M , Winbo Annika , Clur Sally-Ann B , Etheridge Susan P , Ackerman Michael J , Horigome Hitoshi , Herberg Ulrike , Dagradi Federica , Spazzolini Carla , Killen Stacy A S , Wacker-Gussmann Annette , Wilde Arthur A M , Sinkovskaya Elena , Abuhamad Alfred , Torchio Margherita , Ng Chai-Ann , Rydberg Annika , Schwartz Peter J , Cuneo Bettina F
Published: November 2023

Aims

In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS.

Methods and results

In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7–42 weeks’ GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.

Conclusion

Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant’s a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.
A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study)
Authors: Jonmundsson Thorarinn , Steindorsdottir Anna E , Austin Thomas R , Frick Elisabet A , Axelsson Gisli T , Launer Lenore , Psaty Bruce M , Loureiro Joseph , Orth Anthony P , Aspelund Thor , Emilsson Valur , Floyd James S , Jennings Lori , Gudnason Vilmundur , Gudmundsdottir Valborg
Published: November 2023

Aims

Atrial fibrillation (AF) is associated with high risk of comorbidities and mortality. Our aim was to examine causal and predictive relationships between 4137 serum proteins and incident AF in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study.

Methods and results

The study included 4765 participants, of whom 1172 developed AF. Cox proportional hazards regression models were fitted for 4137 baseline protein measurements adjusting for known risk factors. Protein associations were tested for replication in the Cardiovascular Health Study (CHS). Causal relationships were examined in a bidirectional, two-sample Mendelian randomization analysis. The time-dependent area under the receiver operating characteristic curve (AUC)-statistic was examined as protein levels and an AF-polygenic risk score (PRS) were added to clinical risk models. The proteomic signature of incident AF consisted of 76 proteins, of which 63 (83%) were novel and 29 (38%) were replicated in CHS. The signature included both N-terminal prohormone of brain natriuretic peptide (NT-proBNP)-dependent (e.g. CHST15, ATP1B1, and SVEP1) and independent components (e.g. ASPN, AKR1B, and LAMA1/LAMB1/LAMC1). Nine causal candidates were identified (TAGLN, WARS, CHST15, CHMP3, COL15A1, DUSP13, MANBA, QSOX2, and SRL). The reverse causal analysis suggested that most AF-associated proteins were affected by the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide improved the prediction of incident AF events close to baseline with further improvements gained by the AF-PRS at all time points.

Conclusion

The AF proteomic signature includes biologically relevant proteins, some of which may be causal. It mainly reflects an NT-proBNP-dependent consequence of the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide is a promising marker for incident AF in the short term, but risk assessment incorporating a PRS may improve long-term risk assessment.
How do adolescents experience the decision-making process on travel mode choice?
Authors: Renninger Denise , Reimers Anne K , Marzi Isabel , Beck Franziska , Krieger Claus , Demetriou Yolanda
Published: November 2023

Active travel can contribute to multiple health benefits in youth. Previous research has identified several factors influencing travel behavior. This study investigates how adolescents process these factors during their decision-making process on travel mode choice. Semi-structured interviews were conducted with 13 adolescents (11–14 years) and analysed using deductive–inductive thematic analysis. Four themes were generated from which the decision-making process on mode choice was conceptualized according to adolescents. The step-by-step process in which travel mode options were gradually reduced, was dependent on the context (Theme 1), the perceived availability of travel mode choice options, which was influenced by factors beyond the individual’s perceived control (Theme 2), and on adolescents’ pros/cons assessment to identify the most convenient option. Adolescents’ habitually used travel mode influenced the decision at several stages throughout the process (Theme 4). To promote healthy travel behaviors, interventions should consider contextual circumstances, balance between enabling autonomous choices and promoting advantages of active travel modes, address individual travel modes and include practices that foster conscious processing of decision-making.
Diverse O-methyltransferases catalyze the biosynthesis of floral benzenoids that repel aphids from the flowers of waterlily Nymphaea prolifera
Authors: Liu Guanhua , Fu Jianyu , Wang Lingyun , Fang Mingya , Zhang Wanbo , Yang Mei , Yang Xuemin , Xu Yingchun , Shi Lin , Ma Xiaoying , Wang Qian , Chen Hui , Yu Cuiwei , Yu Dongbei , Chen Feng , Jiang Yifan
Published: November 2023

Nymphaea is a key genus of the ANA grade (Amborellales, Nymphaeales, and Austrobaileyales) of basal flowering plants, which serve as a key model to study the early evolution of floral traits. In this study, we comprehensively investigated the emission, biosynthesis, and biological function of the floral scent in a night-blossoming waterlily Nymphaea prolifera. The headspace volatile collection combined with GC–MS analysis showed that the floral scent of N. prolifera is predominately comprised by methylated benzenoids including anisole, veratrole, guaiacol, and methoxyanisole. Moreover, the emission of these floral benzenoids in N. prolifera exhibited temporal and spatial pattern with circadian rhythm and tissue specificity. By creating and mining transcriptomes of N. prolifera flowers, 12 oxygen methyltransferases (NpOMTs) were functionally identified. By in vitro enzymatic assay, NpOMT3, 6, and 7 could produce anisole and NpOMT5, 7, 9, produce guaiacol, whereas NpOMT3, 6, 9, 11 catalyzed the formation of veratrole. Methoxyanisole was identified as the universal product of all NpOMTs. Expression patterns of NpOMTs provided implication for their roles in the production of the respective benzenoids. Phylogenetic analysis of OMTs suggested a Nymphaea-specific expansion of the OMT family, indicating the evolution of lineage-specific functions. In bioassays, anisole, veratrole, and guaiacol in the floral benzenoids were revealed to play the critical role in repelling waterlily aphids. Overall, this study indicates that the basal flowering plant N. prolifera has evolved a diversity and complexity of OMT genes for the biosynthesis of methylated benzenoids that can repel insects from feeding the flowers. These findings provide new insights into the evolutional mechanism and ecological significance of the floral scent from early-diverged flowering plants.
Do the attitudes and practices of Australian pharmacists reflect a need for education and training to provide care for people who are transgender?
Authors: Chaudhary Swapna , Lindsay Daniel , Ray Robin , Glass Beverley D
Published: November 2023

Background

Many transgender and gender diverse (TGD) people access care through community pharmacy in Australia. However, there is limited information available about the role of Australian pharmacists in providing care for TGD people.

Objective

To explore the attitudes, practices, and training needs of pharmacists in the provision of care for TGD people in Australia.

Method

Pharmacists Australia-wide were invited to participate in an online survey through Facebook, e-newsletters of pharmacy organizations and a professional pharmacy journal. Quantitative data were analysed for descriptive and inferential statistics. A Fisher exact test was used to investigate associations between two variables. Results with P value <0.05 were considered statistically significant. Content analysis was used to analyse data from free-text responses.

Result

Of the 169 respondents, the majority were female (75.1%), aged below 40 years (74%) and with less than 10 years of working experience as a pharmacist (58%). Although 95% of the sample agreed that they had an important role in the provision of care for TGD people, only 29.6% were confident about their knowledge of pharmacotherapeutic treatments for gender affirmation. Only 2.4% had received education about TGD care at university, and only 5.3% received any TGD healthcare training over the past 5 years.

Conclusion

Although pharmacists had a positive attitude and recognized their role in TGD care, they expressed a lack of confidence in their knowledge to be a barrier to providing quality care. Most recommended the need for more education about TGD healthcare in pharmacy curricula and continuous professional education activities.
Effects of vaccination on the two-strain transmission dynamics of COVID-19: Dougherty County, Georgia, USA, as a case study
Authors: Pantha Buddhi , Mohammed-Awel Jemal , Vaidya Naveen K
Published: November 2023

The emergence of multiple strains of SARS-COV-2 has made it complicated to predict and control the COVID-19 pandemic. Although some vaccines have been effective in reducing the severity of the disease, these vaccines are designed for a specific strain of the virus and are usually less effective for other strains. In addition, the waning of vaccine-induced immunity, reinfection of recovered people, and incomplete vaccination are challenging to the vaccination program. In this study, we developed a detailed model to describe the multi-strain transmission dynamics of COVID-19 under vaccination. We implemented our model to examine the impact of inter-strain transmission competition under vaccination on the critical outbreak indicators: hospitalized cases, undiagnosed cases, basic reproduction numbers, and the overtake-time by a new strain to the existing strain. In particular, our results on the dependence of the overtake-time on vaccination rates, progression-to-infectious rate, and relative transmission rates provide helpful information for managing a pandemic with circulating two strains. Furthermore, our results suggest that a reduction in the relative transmission rates and a decrease in vaccination dropout rates or an increase in vaccination rates help keep the reproduction number of both strains below unity and keep the number of hospitalized cases and undiagnosed cases at their lowest levels. Moreover, our analysis shows that the second and booster-dose vaccinations are useful for further reducing the reproduction number.
Streptococcus suis Serotype 2 Type IV Secretion Effector SspA-1 Induces Proinflammatory Cytokine Production via TLR2 Endosomal and Type I Interferon Signaling
Authors: Yin Supeng , Yuan Mengmeng , Zhang Sirui , Chen Hongdan , Zhou Jing , He Tongyu , Li Gang , Yu Yanlan , Zhang Fan , Li Ming , Zhao Yan
Published: November 2023

The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1–triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1–induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1–induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.
Climate Change and Violent Conflict in the Middle East and North Africa
Authors: Kim Kyungmee , Garcia Tània Ferré
Published: November 2023

Previous research has demonstrated that climate change can escalate the risks for violent conflict through various pathways. Existing evidence suggests that contextual factors, such as migration and livelihood options, governance arrangements, and existing conflict dynamics, can influence the pathways through which climate change leads to conflict. This important insight leads to an inquiry to identify sets of conditions and processes that make climate-related violent conflict more likely. In this analytic essay, we conduct a systematic review of scholarly literature published during the period 1989–2022 and explore the climate-conflict pathways in the Middle East and North Africa (MENA) region. Through the systematic review of forty-one peer-reviewed publications in English, we identify that society’s ability to cope with the changing climate and extreme weather events is influenced by a range of factors, including preceding government policies that led to the mismanagement of land and water and existing conflict dynamics in the MENA region. Empirical research to unpack the complex and diverse relationship between the climate shocks and violent conflict in the MENA region needs advancing. Several avenues for future research are highlighted such as more studies on North Africa and the Gulf region, with focus on the implications of floods and heatwaves, and exploring climate implications on non-agriculture sectors including the critical oil sector.
Emergence of a novel ISS1N-optrA-carrying transposon within an integrative and conjugative element from Streptococcus parasuis
Authors: Dai Xingyang , Sun Junjie , Zhao Wenbin , Wang Jianzhong , Zhang Xiaohui , Liu Xiao , Li Aijuan , Zhao Jiaqi , Han Peizhao , Wang Xiaoming , Wang Liping , Huang Jinhu
Published: November 2023

Objectives

To investigate the genetic context and transferability of the oxazolidinone resistance gene optrA in a Streptococcus parasuis isolate.

Methods

The optrA-carrying S. parasuis isolate SFJ45 was characterized by PCR, antimicrobial susceptibility testing, complete genome sequencing and bioinformatic analysis. The transferability of optrA was verified by conjugation, followed by SmaI-PFGE and Southern blotting.

Results

The S. parasuis isolate SFJ45 was positive for optrA, mef(A), msr(D), erm(B), tetAB(P)′, tet(M), aadE, aphA3, catQ, dfrG and mdt(A), conferring an MDR phenotype. The optrA gene was flanked by ISS1N at both termini in the same orientation, representing a novel 8750 bp pseudo-compound transposon, organized as the ISS1N-hth-clb-4hp-optrA-2hp-ISS1N structure. The ISS1N-optrA-carrying transposon was further inserted within an integrative and conjugative element, ICESpsuSFJ45, at 3′ end of the fda gene. Conjugative transfer of the ISS1N-optrA-carrying transposon with ICESpsuSFJ45 was observed from S. parasuis to Streptococcus suis at a frequency of (1.01 ± 3.12) × 10−7.

Conclusions

ISS1N was found to be associated with optrA spreading for the first time. Integration of the ISS1N-optrA transposon within ICESpsuSFJ45 may lead to the co-selection of optrA with other antimicrobial resistance genes, contributing to its horizontal transfer from S. parasuis to clinically more important bacterial pathogens.
A proteomic perspective on the resistance response of Klebsiella pneumoniae to antimicrobial peptide PaDBS1R1
Authors: Fleitas Osmel , Fontes Wagner , De Souza Camila M , Da Costa Mylena C , Cardoso Marlon H , Castro Mariana S , Sousa Marcelo V , Ricart Carlos A O , Ramada Marcelo H S , Duque Harry M , Porto William F , Silva Osmar N , Franco Octávio L
Published: November 2023

Background

The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which resistance mechanisms could be involved.

Objectives

Identify via label-free shotgun proteomics the K. pneumoniae resistance mechanisms developed against PaDBS1R1.

Methods

An adaptive laboratory evolution experiment was performed to obtain a PaDBS1R1-resistant K. pneumoniae lineage. Antimicrobial susceptibility was determined through microdilution assay. Modifications in protein abundances between the resistant and sensitive lineages were measured via label-free quantitative shotgun proteomics. Enriched Gene Ontology terms and KEGG pathways were identified through over-representation analysis. Data are available via ProteomeXchange with identifier PXD033020.

Results

K. pneumoniae ATCC 13883 parental strain challenged with increased subinhibitory PaDBS1R1 concentrations allowed the PaDBS1R1-resistant K. pneumoniae lineage to emerge. Proteome comparisons between PaDBS1R1-resistant K. pneumoniae and PaDBS1R1-sensitive K. pneumoniae under PaDBS1R1-induced stress conditions enabled the identification and quantification of 1702 proteins, out of which 201 were differentially abundant proteins (DAPs). The profiled DAPs comprised 103 up-regulated proteins (adjusted P value < 0.05, fold change ≥ 2) and 98 down-regulated proteins (adjusted P value < 0.05, fold change ≤ 0.5). The enrichment analysis suggests that PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery could be relevant resistance mechanisms against PaDBS1R1.

Conclusions

Based on experimental evolution and a label-free quantitative shotgun proteomic approach, we showed that K. pneumoniae developed resistance against PaDBS1R1, whereas PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery appear to be relevant resistance mechanisms against PaDBS1R1.
Glycoside hydrolase family 32 enzymes from Bombella spp. catalyze the formation of high-molecular weight fructans from sucrose
Authors: Härer Luca , Ernst Luise , Bechtner Julia , Wefers Daniel , Ehrmann Matthias A
Published: November 2023

Aims

Acetic acid bacteria of the genus Bombella have not been reported to produce exopolysaccharides (EPS). In this study, the formation of fructans by B. apis TMW 2.1884 and B. mellum TMW 2.1889 was investigated.

Methods and Results

Out of eight strains from four different Bombella species, only B. apis TMW 2.1884 and B. mellum TMW 2.1889 showed EPS formation with 50 g l−1 sucrose as substrate. Both EPS were identified as high-molecular weight (HMW) polymers (106–107 Da) by asymmetric flow field-flow fractionation coupled to multi angle laser light scattering and UV detecors (AF4-MALLS/UV) and high performance size exclusion chromatography coupled to MALLS and refractive index detectors (HPSEC-MALLS/RI) analyses. Monosaccharide analysis via trifluoroacetic acid hydrolysis showed that both EPS are fructans. Determination of glycosidic linkages by methylation analysis revealed mainly 2,6-linked fructofuranose (Fruf) units with additional 2,1-linked Fruf units (10%) and 2,1,6-Fruf branched units (7%). No glycoside hydrolase (GH) 68 family genes that are typically associated with the formation of HMW fructans in bacteria could be identified in the genomes. Through heterologous expression in Escherichia coli Top10, an enzyme of the GH32 family could be assigned to the catalysis of fructan formation. The identified fructosyltransferases could be clearly differentiated phylogenetically and structurally from other previously described bacterial fructosyltransferases.

Conclusions

The formation of HMW fructans by individual strains of the genus Bombella is catalyzed by enzymes of the GH32 family. Analysis of the fructans revealed an atypical structure consisting of 2,6-linked Fruf units as well as 2,1-linked Fruf units and 2,1,6-Fruf units.
Systematic review and longitudinal analysis of implementing Artificial Intelligence to predict clinical deterioration in adult hospitals: what is known and what remains uncertain
Authors: van der Vegt Anton H , Campbell Victoria , Mitchell Imogen , Malycha James , Simpson Joanna , Flenady Tracy , Flabouris Arthas , Lane Paul J , Mehta Naitik , Kalke Vikrant R , Decoyna Jovie A , Es’haghi Nicholas , Liu Chun-Huei , Scott Ian A
Published: November 2023

Objective

To identify factors influencing implementation of machine learning algorithms (MLAs) that predict clinical deterioration in hospitalized adult patients and relate these to a validated implementation framework.

Materials and methods

A systematic review of studies of implemented or trialed real-time clinical deterioration prediction MLAs was undertaken, which identified: how MLA implementation was measured; impact of MLAs on clinical processes and patient outcomes; and barriers, enablers and uncertainties within the implementation process. Review findings were then mapped to the SALIENT end-to-end implementation framework to identify the implementation stages at which these factors applied.

Results

Thirty-seven articles relating to 14 groups of MLAs were identified, each trialing or implementing a bespoke algorithm. One hundred and seven distinct implementation evaluation metrics were identified. Four groups reported decreased hospital mortality, 1 significantly. We identified 24 barriers, 40 enablers, and 14 uncertainties and mapped these to the 5 stages of the SALIENT implementation framework.

Discussion

Algorithm performance across implementation stages decreased between in silico and trial stages. Silent plus pilot trial inclusion was associated with decreased mortality, as was the use of logistic regression algorithms that used less than 39 variables. Mitigation of alert fatigue via alert suppression and threshold configuration was commonly employed across groups.

Conclusions

: There is evidence that real-world implementation of clinical deterioration prediction MLAs may improve clinical outcomes. Various factors identified as influencing success or failure of implementation can be mapped to different stages of implementation, thereby providing useful and practical guidance for implementers.
Implementation and evaluation of an electronic health record-integrated app for postpartum monitoring of hypertensive disorders of pregnancy using patient-contributed data collection
Authors: Dullabh Prashila , Heaney-Huls Krysta K , Chiao Andrew B , Callaham Melissa G , Desai Priyanka , Gauthreaux Nicole A , Kashyap Nitu , Lobach David F , Boxwala Aziz
Published: November 2023

Remote monitoring of women experiencing hypertensive disorders of pregnancy (HDP) can provide timely life-saving data, particularly if these data are integrated into existing patient and clinical workflows. This pilot intervention of a smartphone application (app) for postpartum monitoring of hypertensive disorders integrates patient-contributed data into electronic health records (EHRs) to support monitoring and clinical decision-making. Results from the evaluation of the pilot highlight the resources needed when implementing the app, challenges for integrating an app into the EHR, and the usability and utility of the HDP monitoring app for patient and clinician users. The implementation team’s key observations included the importance of a local clinical champion, more robust patient involvement and support for the remote patient monitoring program, an impetus for EHR developers to adopt data integration standards, and a need to expand the capabilities of the standards to support interventions using patient-contributed data.
The Largest Subunit of Human TFIIIC Complex, TFIIIC220, a Lysine Acetyltransferase Targets Histone H3K18
Authors: Basu Moumita , Bhatt Rohini , Sharma Anjali , Boopathi Ramachandran , Das Sadhan , Kundu Tapas K
Published: November 2023

TFIIIC is a multi-subunit complex required for tRNA transcription by RNA polymerase III. Human TFIIIC holo-complex possesses lysine acetyltransferase activity that aids in relieving chromatin-mediated repression for RNA polymerase III-mediated transcription and chromatin assembly. Here we have characterized the acetyltransferase activity of the largest and DNA-binding subunit of TFIIIC complex, TFIIIC220. Purified recombinant human TFIIIC220 acetylated core histones H3, H4 and H2A in vitro. Moreover, we have identified the putative catalytic domain of TFIIIC220 that efficiently acetylates core histones in vitro. Mutating critical residues of the putative acetyl-CoA binding ‘P loop’ drastically reduced the catalytic activity of the acetyltransferase domain. Further analysis showed that the knockdown of TFIIIC220 in mammalian cell lines dramatically reduces global H3K18 acetylation level, which was rescued by overexpression of the putative acetyltransferase domain of human TFIIIC220. Our findings indicated a possibility of a crucial role for TFIIIC220 in maintaining acetylation homeostasis in the cell.
A Retrospective Case-Control Study of Eravacycline for the Treatment of Carbapenem-Resistant Acinetobacter Infections in Patients With Burn Injuries
Authors: Alexander Connor , Hill David
Published: November 2023

Thermal injuries lead to a deficiency in one’s natural, protective barrier, resulting in increased susceptibility to pathogens, and often require multiple courses of broad-spectrum antibiotics. Eravacycline (ERA) has shown adequate in vitro activity against multiple multi-drug resistant (MDR) pathogens including Acinetobacter sp. Due to the increasing prevalence of MDR bacteria and the heightened susceptibility of patients with burns to infection, studies are needed to examine the clinical effect of eravacycline in this population. The objective of this retrospective, case-control study was to compare the outcomes of patients with thermal injuries treated with eravacycline versus a matched control for carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Patients with thermal injury admitted to an American Burn Associated-verified burn center from May 1, 2019 to July 31, 2022, who received eravacycline, were randomly matched 4:1 to a historical cohort using a previously established, de-identified dataset of patients treated with colistimethate sodium (CMS) in the same burn center (March 1, 2009 to March 31, 2014), based on % total body surface area (%TBSA), age, and CRAB. A composite favorable outcome was defined as 30-day survival, completion of the course, lack of 14-day recurrence, and lack of acute kidney injury (AKI). Treatment with eravacycline over CMS was not more or less likely to be associated with a favorable response [odds ratio (95% confidence interval), 2.066 (0.456–9.361), P = .347]. Patients treated with CMS had nearly 9-fold higher odds of new-onset AKI versus ERA [8.816 (0.911–85.308), P = .06]. Adverse events were uncommon in the ERA group. There was no difference in mortality.
Regularized deep learning for unsupervised random noise attenuation in poststack seismic data
Authors: Song Chengyun , Guo Shutao , Xiong Chuanchao , Tuo Jiying
Published: November 2023

Deep learning methods achieve excellent noise reduction performances in seismic data processing compared with traditional methods. However, deep learning usually requires a large number of pairwise noisy-clean training data, which is an extremely challenging task. In this paper, an unsupervised approach without clean seismic data is proposed to suppress random noise. Seismic data is divided into odd and even traces, which serve as the input and output of the depth network, so that the proposed algorithm can be trained directly on the original data. What is more, the proposed method introduces two regularization terms to solve the over-smoothing problem caused by reconstruction of adjacent traces. The first term considers an ideal denoising network that does not cause oversmooth as a constraint, while the second term considers the structural information existing in seismic data. Experiments on synthetic post-stack data illustrate that the proposed method obtain a higher signal-to-noise ratio than the comparison methods. In the application of field post-stack seismic data, the proposed method can effectively maintain the seismic amplitude and generate good spectral characteristics.
Impact of pain and adverse health outcomes on long-term US testicular cancer survivors
Authors: Dinh Paul C , Monahan Patrick O , Fosså Sophie D , Sesso Howard D , Feldman Darren R , Dolan M Eileen , Nevel Kathryn , Kincaid John , Vaughn David J , Martin Neil E , Sanchez Victoria A , Einhorn Lawrence H , Frisina Robert , Fung Chunkit , Kroenke Kurt , Travis Lois B
Published: November 2023

Background

No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain.

Methods

Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a β^  of more than 2 are clinically important and reported below.

Results

Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38–53 years; median time since chemotherapy = 10.7 years, IQR = 7.2–16.0 years), median adverse health outcomes number was 5 (IQR = 3–7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P < .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (β^ = −3.72; P = .001), diabetes (β^ = −4.41; P = .037), obesity (β^ = −2.01; P = .036), and fatigue (β^ = −8.58; P < .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (β^ = 3.63; P = .0006). Risk factors for pain-related functional impairment included lower extremity location (β^ = 2.15; P = .04) and concomitant peripheral artery disease (β^ = 4.68; P < .001). Global physical health score reductions were associated with diabetes (β^ = −3.81; P = .012), balance or equilibrium problems (β^ = −3.82; P = .003), cognitive dysfunction (β^ = −4.43; P < .0001), obesity (β^ = −3.09; P < .0001), peripheral neuropathy score (β^ = −2.12; P < .0001), and depression (β^ = −3.17; P < .0001).

Conclusions

Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment.