bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Outcomes Associated With Teduglutide Use in Patients With Both Short Bowel Syndrome and Crohn’s Disease
Authors: Siu Rex K , Karime Christian , Hashash Jana G , Kinnucan Jami , Picco Michael F , Farraye Francis A
Published: January 2024

Introduction

Crohn’s disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide.

Methods

Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output.

Results

We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PN + IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances (P < .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0).

Conclusions

This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.
Cybersecurity when working from home during COVID-19: considering the human factors
Authors: Whitty Monica T , Moustafa Nour , Grobler Marthie
Published: January 2024

This research examined the lives of Australian employees who moved to work from home during COVID-19. Taking a unique approach to cybersecurity, we sought to gain insights into the intermingling of individuals’ personal lives and technology to inform policies and educational programmes. The study employed interpretative phenomenological analysis to understand 27 participants’ lived experiences under lockdown. We found that psychological (e.g. stress, anxiety, confidence, motivation) and sociological (e.g. sharing physical spaces, digital divide) factors impacted employees’ likelihood and ability to engage in effective cybersecurity practices. So did new ways of using technology (e.g. teaching via Zoom), which elucidated unexpected but significant security concerns (e.g. naked children in virtual classrooms). We suggest that cyber educators and policymakers take a Vygotskian approach, which considers that social interaction is central to learning. This assumption means that personal factors must be considered instead of a ‘one-size-fits-all approach’. We argue that organizations should think about approaches that consider the employees’ psychological state before training (and perhaps find ways to reduce anxiety), helping employees redesign their home workspaces to ensure privacy and concentration, and updating employees’ digital devices. Practitioners and scholars can also apply these results post-COVID-19, especially if the ‘new working normal’ provides options for employees to work from home.
Clinical and radiological features of malformed mesiodens in the nasopalatine canal: an observational study
Authors: Kim Yu-Ri , Lee Yu-Min , Huh Kyung-Hoe , Yi Won-Jin , Heo Min-Suk , Lee Sam-Sun , Kim Jo-Eun
Published: January 2024

Objectives

The purpose of this study is to investigate the morphological changes that occur when mesiodens is located within the nasopalatine canal, as well as clinical characteristics.

Methods

Clinical records and CT images of patients who had mesiodens in the nasopalatine canal were retrospectively analysed. In addition to demographic information, clinical symptoms and complications associated with extraction of mesiodens were recorded. Using CT images, number, location, size, and tooth morphology were evaluated.

Results

This study included 32 patients and 38 mesiodens within the nasopalatine canal. Supernumerary teeth exhibited a characteristic feature of thin and elongated shape in the canal (narrow width and elongation were observed in 96.6% and 53.3% of the patients, respectively). Fusion was found in 4 patients and dilaceration in 12. A complication occurred in 2 patients, which was tooth remnant, not a neurologic complication. Only 5 mesiodens could be detected in the nasopalatine canal on panoramic images.

Conclusions

Morphological abnormalities in mesiodens within the nasopalatine canal were frequently detected, and these could be effectively diagnosed through 3D imaging analysis.
National adoption of an esophageal cell collection device for Barrett’s esophagus surveillance: impact on delay to investigation and pathological findings
Authors: Chien Siobhan , Glen Paul , Penman Ian , Bryce Gavin , Cruickshank Neil , Miller Michael , Crumley Andrew , Fletcher Jonathan , Phull Perminder , Gunjaca Ivan , Robertson Kevin , Apollos Jeyakumar , Fullarton Grant ,   the CytoSCOT group
Published: January 2024

High quality Barrett’s esophagus surveillance is crucial to detect early neoplastic changes. An esophageal cell collection device (OCCD) was introduced as a triage tool for Barrett’s surveillance. This study aims to evaluate whether the Scottish OCCD program (CytoSCOT) has reduced delays to Barrett’s surveillance, and whether delayed surveillance negatively impacts endoscopic pathology. All patients undergoing OCCD testing for Barrett’s surveillance across 11 Scottish health boards between 14/9/2020 and 13/9/2022 were identified. Patients were dichotomised into two groups (Year 1 vs. Year 2), with individual records interrogated to record demographics, recommended surveillance interval, time from last endoscopy to OCCD test, and OCCD result. Patients were deemed high-risk if the OCCD demonstrated atypia and/or p53 positivity. Further analysis was performed on patients who underwent endoscopy within 12 months of OCCD testing. A total of 3223 OCCD tests were included in the analysis (1478 in Year 1; 1745 in Year 2). In Year 1 versus Year 2, there was a longer median delay to surveillance (9 vs. 5 months; P < 0.001), increased proportion of patients with delayed surveillance (72.6% vs. 57.0%; P < 0.001), and more high-risk patients (12.0% vs. 5.3%; P < 0.001). 425/3223 patients (13.2%) were further investigated with upper gastrointestinal endoscopy, 57.9% of which were high-risk. As surveillance delay increased beyond 24 months, high-risk patients were significantly more likely to develop dysplasia or malignancy (P = 0.004). Delayed Barrett’s esophagus surveillance beyond 24 months is associated with increased risk of pre-cancerous pathology. The CytoSCOT program has reduced delays in surveillance, promoting earlier detection of dysplasia and reducing burden on endoscopy services.
The limited antegrade subintimal tracking technique to retrieve a trapped rotablator burr: a case report
Authors: Maznyczka Annette , Mozid Abdul
Published: January 2024

Background

Burr entrapment is a rare, but potentially serious complication of rotablation. This report describes the percutaneous options available for Rota burr retrieval.

Case summary

A 62-year-old Caucasian man with stable angina presented for percutaneous coronary intervention. Attempted rotablation with a 1.75 mm burr resulted in Rota burr entrapment, in the heavily calcified proximal right coronary artery. A chronic total occlusion angioplasty technique (limited antegrade subintimal tracking) was successfully used to remove the trapped Rota burr, by enabling subintimal dilatation to externally crush plaque and dislodge the burr. The angioplasty procedure was then completed using the wire that had a short subintimal passage, before re-entering the true lumen.

Discussion

The mechanism for Rota burr entrapment, in this case, was initiating rotablation on the heavily calcified lesion and not more proximal to allow a pecking motion. The learning points are (i) to start the rotablator several millimetres proximal to the actual lesion, and (ii) if unable to wire alongside a trapped Rota burr in the true lumen, then subintimal crossing and balloon dilatation in the subintimal space may work to dislodge the burr.
Ablation of atrial flutter in a patient after Fontan procedure: a case report of challenging access to the common atrium
Authors: Maslova Vera , Demming Thomas , Nonnenmacher Marc , Voges Inga , Lyan Evgeny
Published: January 2024

Background

In patients with a total cavopulmonary connection in Fontan circulation, the access to the common atrium (CA) during a catheter ablation can be challenging, even in the presence of fenestration in an intra-atrial lateral tunnel (IALT). In our department, the fenestration is typically marked with metal clips (MCs). To the best of our knowledge, there is no previous report of balloonoplasty of clipped fenestration.

Case summary

A 19-year-old male with hypoplastic left heart syndrome (HLHS) was scheduled for catheter ablation of recurrent atrial tachycardia. He was diagnosed with HLHS prenatally and underwent a stepwise surgical palliation. Fontan circulation was completed with the creation of a fenestrated IALT. The fenestration was marked by four MCs. During the ablation procedure, the passage of the steerable sheath with mapping catheter to the CA was prevented by a small fenestration size and rigidness of the edges of the fenestration caused by the MCs. Multiple attempts to dilate the fenestration using a peripheric angioplasty balloon failed. Only angioplasty with the ‘balloon-against-dilator’ technique was finally successful. Activation map showed a counterclockwise atrial flutter in the CA; successful ablation was performed.

Discussion

We present a case of challenging access to the CA through a clipped fenestration in a polytetrafluoroethylene baffle for atrial tachycardia ablation. Even though a tunnel fenestration in Fontan patients facilitates access to the CA, the passage of a steerable introducer with a mapping catheter may be challenging due to diameter mismatch and the rigidity of its edges caused by MCs. The balloon-against-dilator technique might be helpful when conventional balloon angioplasty fails.
Innovation and Distribution: an Equilibrium Model of Manufacturing and Retailing
Authors: Bronnenberg Bart J
Published: January 2024

This paper proposes a model of the distribution channel to study the decisions of manufacturers, retailers and consumers. The model is used to study how retail distribution affects manufacturing and consumers. As the cost of distribution falls, the retail sector increases assortment size and allows a larger mass of manufacturers to enter, allowing consumers to buy more variety. Entry primitives in manufacturing and retailing determine vertical pricing power. The equilibrium of the model predicts that the national retail sector is a fraction of the total economy that depends on the demand for variety. It is not affected by, e.g., consumer transportation cost or income. Data support this prediction.
‘A knowledge easely taught, and quickly learned’: learning to sing in Byrd’s England
Authors: Arten Samantha
Published: January 2024

William Byrd published his famous eight ‘Reasons briefely set down by th’auctor, to perswade every one to learne to sing’ in his 1588 Psalmes, sonets and songs. The most important reason to learn to sing, according to Byrd, is that ‘it is a knowledge easely taught, and quickly learned, wher there is a good Master, and an apt Scoler’. The ‘knowledge’ of which Byrd speaks is not only the mechanics of singing but also, or perhaps chiefly, the musical knowledge necessary to sing: the rudiments of musical literacy. This article unpacks Byrd’s claims about music education in Tudor England, placing them in the context of print culture and educational practices. It first considers the options for music education available to different social classes and genders, then turns to close study of music theory treatises and other music educational texts printed in 16th-century England. I examine how these printed materials discussed their own role in the process of educating readers, and interrogate their prevailing claims that gaining musical literacy is ‘plain’ and ‘easie’, and possible ‘without any other help saving this booke’.
Impact of untreated chronic obstructive coronary artery disease on outcomes after transcatheter aortic valve replacement
Authors: Persits Ian , Layoun Habib , Kondoleon Nicholas P , Spilias Nikolaos , Badwan Osamah , Sipko Joseph , Yun James J , Kalra Ankur , Dykun Iryna , Tereshchenko Larisa G , Krishnaswamy Amar , Reed Grant W , Kapadia Samir R , Puri Rishi
Published: January 2024

Background and Aims

In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes.

Methods

The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization.

Results

Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001).

Conclusions

Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year.
Interleukin-22 enhanced the mucosal barrier and inhibited the invasion of Salmonella enterica in human-induced pluripotent stem cell-derived small intestinal epithelial cells
Authors: Yamazaki Fuka , Kobayashi Kyosuke , Mochizuki Junko , Sashihara Toshihiro
Published: January 2024

Human-induced pluripotent stem cell-derived small intestinal epithelial cell (hiPSC-SIEC) monolayers are useful in vitro models for evaluating the gut mucosal barrier; however, their reactivity to cytokines, which are closely related to the regulation of mucosal barrier function, remains unclear. Interleukin (IL)-22 is a cytokine that contributes to regulate the mucosal barrier in the intestinal epithelia. Using microarray and gene set enrichment analysis, we found that hiPSC-SIEC monolayers activate the immune response and enhance the mucosal barrier in response to IL-22. Moreover, hiPSC-SIEC monolayers induced the gene expression of antimicrobials, including the regenerating islet-derived protein 3 family. Furthermore, IL-22 stimulation upregulated Mucin 2 secretion and gene expression of an enzyme that modifies sugar chains, suggesting alteration of the state of the mucus layer of hiPSC-SIEC monolayers. To evaluate its physiological significance, we measured the protective activity against Salmonella enterica subsp. enterica infection in hiPSC-SIEC monolayers and found that prestimulation with IL-22 reduced the number of viable intracellular bacteria. Collectively, these results suggest that hiPSC-SIEC monolayers enhance the mucosal barrier and inhibit infection by pathogenic bacteria in response to IL-22, as previously reported. These results can contribute to the further application of hiPSC-SIECs in evaluating mucosal barriers.
Pro-Brain-Derived Neurotrophic Factor (BDNF), but Not Mature BDNF, Is Expressed in Human Skeletal Muscle: Implications for Exercise-Induced Neuroplasticity
Authors: Edman Sebastian , Horwath Oscar , Van der Stede Thibaux , Blackwood Sarah Joan , Moberg Isabel , Strömlind Henrik , Nordström Fabian , Ekblom Maria , Katz Abram , Apró William , Moberg Marcus
Published: January 2024

Exercise promotes brain plasticity partly by stimulating increases in mature brain-derived neurotrophic factor (mBDNF), but the role of the pro-BDNF isoform in the regulation of BDNF metabolism in humans is unknown. We quantified the expression of pro-BDNF and mBDNF in human skeletal muscle and plasma at rest, after acute exercise (+/− lactate infusion), and after fasting. Pro-BDNF and mBDNF were analyzed with immunoblotting, enzyme-linked immunosorbent assay, immunohistochemistry, and quantitative polymerase chain reaction. Pro-BDNF was consistently and clearly detected in skeletal muscle (40-250 pg mg−1 dry muscle), whereas mBDNF was not. All methods showed a 4-fold greater pro-BDNF expression in type I muscle fibers compared to type II fibers. Exercise resulted in elevated plasma levels of mBDNF (55%) and pro-BDNF (20%), as well as muscle levels of pro-BDNF (∼10%, all P < 0.05). Lactate infusion during exercise induced a significantly greater increase in plasma mBDNF (115%, P < 0.05) compared to control (saline infusion), with no effect on pro-BDNF levels in plasma or muscle. A 3-day fast resulted in a small increase in plasma pro-BDNF (∼10%, P < 0.05), with no effect on mBDNF. Pro-BDNF is highly expressed in human skeletal muscle, particularly in type I fibers, and is increased after exercise. While exercising with higher lactate augmented levels of plasma mBDNF, exercise-mediated increases in circulating mBDNF likely derive partly from release and cleavage of pro-BDNF from skeletal muscle, and partly from neural and other tissues. These findings have implications for preclinical and clinical work related to a wide range of neurological disorders such as Alzheimer’s, clinical depression, and amyotrophic lateral sclerosis.
Gene loss and cis-regulatory novelty shaped core histone gene evolution in the apiculate yeast Hanseniaspora uvarum
Authors: Haase Max A B , Steenwyk Jacob L , Boeke Jef D
Published: January 2024

Core histone genes display a remarkable diversity of cis-regulatory mechanisms despite their protein sequence conservation. However, the dynamics and significance of this regulatory turnover are not well understood. Here, we describe the evolutionary history of core histone gene regulation across 400 million years in budding yeasts. We find that canonical mode of core histone regulation—mediated by the trans-regulator Spt10—is ancient, likely emerging between 320 and 380 million years ago and is fixed in the majority of extant species. Unexpectedly, we uncovered the emergence of a novel core histone regulatory mode in the Hanseniaspora genus, from its fast-evolving lineage, which coincided with the loss of 1 copy of its paralogous core histone genes. We show that the ancestral Spt10 histone regulatory mode was replaced, via cis-regulatory changes in the histone control regions, by a derived Mcm1 histone regulatory mode and that this rewiring event occurred with no changes to the trans-regulator, Mcm1, itself. Finally, we studied the growth dynamics of the cell cycle and histone synthesis in genetically modified Hanseniaspora uvarum. We find that H. uvarum divides rapidly, with most cells completing a cell cycle within 60 minutes. Interestingly, we observed that the regulatory coupling between histone and DNA synthesis was lost in H. uvarum. Our results demonstrate that core histone gene regulation was fixed anciently in budding yeasts, however it has greatly diverged in the Hanseniaspora fast-evolving lineage.
Murine Myoblasts Exposed to SYUIQ-5 Acquire Senescence Phenotype and Differentiate into Sarcopenic-Like Myotubes, an In Vitro Study
Authors: Gerosa Laura , Malvandi Amir Mohammad , Gomarasca Marta , Verdelli Chiara , Sansoni Veronica , Faraldi Martina , Ziemann Ewa , Olivieri Fabiola , Banfi Giuseppe , Lombardi Giovanni
Published: January 2024

The musculoskeletal system is one of the most affected organs by aging that correlates well with an accumulation of senescent cells as for other multiple age-related pathologies. The molecular mechanisms underpinning muscle impairment because of senescent cells are still elusive. The availability of in vitro model of skeletal muscle senescence is limited and restricted to a small panel of phenotypic features of these senescent cells in vivo. Here, we developed a new in vitro model of senescent C2C12 mouse myoblasts that, when subjected to differentiation, the resulting myotubes showed sarcopenic features. To induce senescence, we used SYUIQ-5, a quindoline derivative molecule inhibitor of telomerase activity, leading to the expression of several senescent hallmarks in treated myoblasts. They had increased levels of p21 protein accordingly with the observed cell cycle arrest. Furthermore, they had enhanced SA-βgalactosidase enzyme activity and phosphorylation of p53 and histone H2AX. SYUIQ-5 senescent myoblasts had impaired differentiation potential and the resulting myotubes showed increased levels of ATROGIN-1 and MURF1, ubiquitin ligases components responsible for protein degradation, and decreased mitochondria content, typical features of sarcopenic muscles. Myotubes differentiated from senescent myoblasts cultures release increased levels of MYOSTATIN that could affect skeletal muscle cell growth. Overall, our data suggest that a greater burden of senescent muscle cells could contribute to sarcopenia. This study presents a well-defined in vitro model of muscle cell senescence useful for deeper investigation in the aging research field to discover new putative therapeutic targets and senescence biomarkers associated with the aged musculoskeletal system.
Changes in Expression of Key Genes in Alzheimer’s Disease: A Specific Brain Tissue Change
Authors: Rasmussen Lucas Trevizani , de Labio Roger Willian , dos Santos Mônica Pezenatto , Fredi Bruno Mari , Baisi Chagas Eduardo Federighi , Chen Elizabeth Suchi , Turecki Gustavo , Smith Marília de Arruda Cardoso , Payão Spencer Luiz Marques
Published: January 2024

Alzheimer’s disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.
Body Size, Diet Quality, and Epigenetic Aging: Cross-Sectional and Longitudinal Analyses
Authors: Li Danmeng Lily , Hodge Allison M , Cribb Lachlan , Southey Melissa C , Giles Graham G , Milne Roger L , Dugué Pierre-Antoine
Published: January 2024

Epigenetic age is an emerging marker of health that is highly predictive of disease and mortality risk. There is a lack of evidence on whether lifestyle changes are associated with changes in epigenetic aging. We used data from 1 041 participants in the Melbourne Collaborative Cohort Study with blood DNA methylation measures at baseline (1990–1994, mean age: 57.4 years) and follow-up (2003–2007, mean age: 68.8 years). The Alternative Healthy Eating Index-2010 (AHEI-2010), the Mediterranean Dietary Score, and the Dietary Inflammatory Index were used as measures of diet quality, and weight, waist circumference, and waist-to-hip ratio as measures of body size. Five age-adjusted epigenetic aging measures were considered: GrimAge, PhenoAge, PCGrimAge, PCPhenoAge, and DunedinPACE. Multivariable linear regression models including restricted cubic splines were used to assess the cross-sectional and longitudinal associations of body size and diet quality with epigenetic aging. Associations between weight and epigenetic aging cross-sectionally at both time points were positive and appeared greater for DunedinPACE (per SD: β ~0.24) than for GrimAge and PhenoAge (β ~0.10). The longitudinal associations with weight change were markedly nonlinear (U-shaped) with stable weight being associated with the lowest epigenetic aging at follow-up, except for DunedinPACE, for which only weight gain showed a positive association. We found negative, linear associations for AHEI-2010 both cross-sectionally and longitudinally. Other adiposity measures and dietary scores showed similar results. In middle-aged to older adults, declining diet quality and weight gain may increase epigenetic age, while the association for weight loss may require further investigation. Our study sheds light on the potential of weight management and dietary improvement in slowing aging processes.
Associations Between Walking Speed and Gut Microbiome Composition in Older Men From the MrOS Study
Authors: Farsijani Samaneh , Cauley Jane A , Cawthon Peggy M , Langsetmo Lisa , Orwoll Eric S , Kado Deborah M , Kiel Douglas P , Newman Anne B
Published: January 2024

Background

Gut dysbiosis has been linked to frailty, but its association with early mobility decline is unclear.

Methods

First, we determined the cross-sectional associations between walking speed and the gut microbiome in 740 older men (84 ± 4 years) from the MrOS cohort with available stool samples and 400 m walking speed measured in 2014–2016. Then, we analyzed the retrospective longitudinal associations between changes in 6 m walking speed (from 2005–2006 to 2014–2016, calculated by simple linear equation) and gut microbiome composition among participants with available data (702/740). We determined gut microbiome composition by 16S sequencing and examined diversity, taxa abundance, and performed network analysis to identify differences in the gut microbiome network of fast versus slow walkers.

Results

Faster 400 m walking speed (m/s) was associated with greater microbiome α-diversity (R = 0.11; p = .004). The association between a slower decline in 6 m walking speed and higher α-diversity (R = 0.07; p = .054) approached borderline significance. Faster walking speed and less decline in walking speed were associated with a higher abundance of genus-level bacteria that produce short-chain fatty acids, and possess anti-inflammatory properties, including Paraprevotella, Fusicatenibacter, and Alistipes, after adjusting for potential covariates (p < .05). The gut microbiome networks of participants in the first versus last quartile of walking speed (≤0.9 vs ≥1.2 m/s) exhibited distinct characteristics, including different centrality measures (p < .05).

Conclusions

Our findings suggest a possible relationship between gut microbiome diversity and mobility function, as indicated by the associations between faster walking speed and less decline in walking speed over 10 years with higher gut microbiome diversity in older men.
Mechanism and implications of the post-seismic deformation following the 2021 Mw 7.4 Maduo (Tibet) earthquake
Authors: Chen Fei , Diao Faqi , Haghighi Mahmud Haghshenas , Wang Yuebing , Zhu Yage , Wang Rongjiang , Xiong Xiong
Published: January 2024

A major earthquake shook the Chinese county of Maduo, located in the Songpan-Ganzi terrane on the Tibetan Plateau, on 21 May 2021. Here, we investigate the post-seismic deformation process of this event, with the aim to understand the fault geometry, friction behaviour and regional rheology. To keep the self-consistency between co- and post-seismic deformation models, we first constrain the fault geometry and coseismic slip model of this event, which are directly used in modelling the post-seismic deformation. The coseimsic slip model reveals that the majority of coseismic slip is confined at the middle (3–15 km) of the brittle layer, leading to significant shallow slip deficit. Secondly, we obtain the post-seismic deformation in the first 450 d following the 2021 Maduo earthquake using the GPS and InSAR displacement time-series data. Thirdly, a combined model incorporating afterslip and viscoelastic relaxation is built to explain the observed post-seismic deformation. Our results suggest that the viscoelastic relaxation effect should be considered in the observation period, in order to avoid the unphysical deep afterslip in the ductile lower crustal layer. Combined analysis on viscosities inferred from this study and previous studies suggests a weak lower crust with steady-state viscosity of 1018–1019 Pa s beneath the Songpan-Ganzi terrane, which may give rise to the distributed shear deformation and the development of subparallel secondary faults within the terrane. Besides, the inferred afterslip on uppermost patches of the middle fault segment suggests a rate-strengthening frictional behaviour that may be related to the coseismic slip deficit and rupture arrest of the Maduo earthquake.
Low-strength shear zone in the western Makran subduction zone, southeastern Iran: insights from a receiver function analysis
Authors: Abbasi Sara , Motaghi Khalil , Lucente Francesco Pio , Bianchi Irene
Published: January 2024

To understand the seismic hazard of a subduction zone, it is necessary to know the geometry, location and mechanical characteristics of the interplate boundary below which an oceanic plate is thrust downward. By considering the azimuthal dependence of converted P-to-S (Ps) amplitudes in receiver functions, we have detected the interplate boundary in the Makran subduction zone, revealing significant seismic anisotropy at the base of the accretionary wedge above the slab before it bends down beneath the Jaz Murian basin. This anisotropic feature aligns with a zone of reduced seismic velocity and a high primary/secondary wave velocity ratio (Vp/Vs), as documented in previous studies. The presence of this low-velocity highly anisotropic layer at the base of the accretionary wedge, likely representing a low-strength shear zone, could possibly explain the unusually wide accretionary wedge in Makran. Additionally, it may impact the location and width of the locked zone along the interplate boundary.
Exploring a novel β-1,3-glucanosyltransglycosylase, MlGH17B, from a marine Muricauda lutaonensis strain for modification of laminari-oligosaccharides
Authors: Allahgholi Leila , Derks Maik G N , Dobruchowska Justyna M , Jasilionis Andrius , Moenaert Antoine , Jouy Léonie , Ara Kazi Zubaida Gulshan , Linares-Pastén Javier A , Friðjónsson Ólafur H , Hreggviðsson Guðmundur Óli , Karlsson Eva Nordberg
Published: January 2024

The marine environment, contains plentiful renewable resources, e.g. macroalgae with unique polysaccharides, motivating search for enzymes from marine microorganisms to explore conversion possibilities of the polysaccharides. In this study, the first GH17 glucanosyltransglycosylase, MlGH17B, from a marine bacterium (Muricauda lutaonensis), was characterized. The enzyme was moderately thermostable with Tm at 64.4 °C and 73.2 °C, but an activity optimum at 20 °C, indicating temperature sensitive active site interactions. MlGH17B uses β-1,3 laminari-oligosaccharides with a degree of polymerization (DP) of 4 or higher as donors. Two glucose moieties (bound in the aglycone +1 and +2 subsites) are cleaved off from the reducing end of the donor while the remaining part (bound in the glycone subsites) is transferred to an incoming β-1,3 glucan acceptor, making a β-1,6-linkage, thereby synthesizing branched or kinked oligosaccharides. Synthesized oligosaccharides up to DP26 were detected by mass spectrometry analysis, showing that repeated transfer reactions occurred, resulting in several β-1,6-linked branches. The modeled structure revealed an active site comprising five subsites: three glycone (−3, −2 and −1) and two aglycone (+1 and +2) subsites, with significant conservation of substrate interactions compared to the only crystallized 1,3-β-glucanosyltransferase from GH17 (RmBgt17A from the compost thriving fungus Rhizomucor miehei), suggesting a common catalytic mechanism, despite different phylogenetic origin, growth environment, and natural substrate. Both enzymes lacked the subdomain extending the aglycone subsites, found in GH17 endo-β-glucanases from plants, but this extension was also missing in bacterial endoglucanases (modeled here), showing that this feature does not distinguish transglycosylation from hydrolysis, but may rather relate to phylogeny.
Extended Induction and Prognostic Indicators of Response in Patients Treated with Mirikizumab with Moderately to Severely Active Ulcerative Colitis in the LUCENT Trials
Authors: D’Haens Geert , Higgins Peter D R , Peyrin-Biroulet Laurent , Sands Bruce E , Lee Scott , Moses Richard E , Redondo Isabel , Escobar Rodrigo , Hunter Gibble Theresa , Keohane Anthony , Morris Nathan , Zhang Xin , Arora Vipin , Kobayashi Taku
Published: January 2024

Background

Efficacy and safety of mirikizumab, a p19-targeted anti-interleukin-23 monoclonal antibody, for moderately to severely active ulcerative colitis was demonstrated previously. We evaluated clinical response, baseline characteristics, and clinical status in patients not responding by 12 weeks (W) of induction who then received extended induction treatment.

Method

Patients unresponsive to 300 mg of intravenous (IV) mirikizumab every 4 weeks by W12 received 3 additional 300 mg IV doses every 4 weeks. Week-4 responders received 200 mg mirikizumab every 4 weeks subcutaneously until W52. Patients responding by W12 but subsequently losing response received rescue therapy with 300 mg IV for 3 doses every 4 weeks. Logistic regression modelling was performed for patients not achieving W12 clinical response to assess baseline characteristics and W12 efficacy parameters and potential prognostic factors of clinical response at W24.

Results

Of patients not achieving clinical response during induction, 53.7% achieved response following extended induction. After 52W, 72.2%, 43.1%, and 36.1% of patients achieved clinical response, endoscopic, and clinical remission, respectively. Of induction responders who subsequently lost response, 63.2% and 36.8% achieved symptomatic response and remission, respectively, after receiving rescue therapy No prior biologic or tofacitinib treatment, no immunomodulators at baseline, age older than 40 years, and W12 modified Mayo Score improvement were positively associated with a response to extended induction. The safety profile was similar to initial induction, with 38.3% treatment emergent adverse events, mostly mild.

Conclusion

With “extended induction,” total of 80.3% mirikizumab-treated patients achieved clinical response by W24. Potential prognostic factors determining response include disease severity, disease phenotype, C-reactive protein, and previous biologic therapy.
Clinical evaluation of the impact of mediastinal tumour size on the subxiphoid approach video-assisted thoracoscopic surgery
Authors: Tang Muhu , Liu Jiacong , Shuai Yongfeng , Wang Luming , Huang Xuhua , Lv Wang , Lin Xu , Zhu Linhai , Hu Jian
Published: January 2024

OBJECTIVES

The application of video-assisted thoracoscopic surgery (VATS) for relatively large mediastinal tumours (≥5.0 cm) has been a subject of debate, and few studies have investigated the subxiphoid approach VATS in different tumour size categories. The study aims to compare the efficacy of the subxiphoid approach VATS for achieving curative outcomes based on tumour size categories (<3.0, 3.0–4.9 and 5.0–10.0 cm).

METHODS

A total of 165 patients with anterior mediastinal tumours who underwent surgery at our hospital between January 2018 and July 2022 were consecutively enrolled, categorized according to tumour size—group A (<3.0 cm): 58, group B (3.0–4.9 cm): 70 and group C (5.0–10.0 cm): 37. Clinical baseline data, intraoperative and postoperative outcomes, and postoperative complications were analysed.

RESULTS

The study revealed significant differences in operation time among the 3 groups (group A: 103.4 ± 36.1, group B: 106.4 ± 35.2, group C: 127.4 ± 44.8; P < 0.05) as well as in the volume of drainage (group A: 273.3 ± 162.0, group B: 411.9 ± 342.6, group C: 509.7 ± 543.7; P < 0.05). However, no differences were seen in blood loss, drainage duration, postoperative hospital stay and duration of postoperative oral analgesics. Additionally, the incidence of postoperative complications did not exhibit significant differences across these groups.

CONCLUSIONS

Subxiphoid approach VATS is considered a feasible and safe surgical method for large-sized anterior mediastinal tumours (5.0–10.0 cm) with no invasion to the surrounding tissues and organs.
Reaction dynamics and early-time behaviour of chemical decontamination
Authors: Murphy S , Vynnycky M , Mitchell S L , O’Kiely D
Published: January 2024

When a hazardous chemical soaks into a porous material such as a concrete floor, it can be difficult to remove. One approach is chemical decontamination, where a cleanser is added to react with and neutralise the contaminating agent. The goal of this paper is to investigate the reaction dynamics and the factors that affect the efficacy of the decontamination procedure. We consider a one-dimensional porous medium initially saturated with an oil-based agent. An aqueous cleanser is applied at the surface, so the two chemicals are immiscible and a boundary forms between them. A neutralising reaction takes place at this boundary in which cleanser and agent are consumed and reaction products are created. This is a Stefan problem, and the boundary between the cleanser and agent moves as the reaction proceeds. Reaction products formed at the interface may dissolve in one or both liquids. This may temporarily prevent cleanser and/or agent from reaching the reaction site, so diffusion of the chemical species, in particular the diffusion of product from the interface, plays a key role. The scenario described above was considered previously by Dalwadi et al. (2017, Mathematical modelling of chemical agent removal by reaction with an immiscible cleanser. SIAM J. Appl. Math., 77, 1937–1961) in the limit where the depth of the porous medium is large compared to the length scale over which concentrations vary inside the medium. Here, we present results that are valid for any ratio between these length scales and an analysis of agent removal times for various dimensionless parameter regimes. We also highlight the emergence of a boundary layer associated with diffusion in the oil phase for early times, where the thickness of the boundary layer is directly proportional to the square root of the time variable.
A bubble model for the gating of Kv channels
Authors: Song Zilong , Eisenberg Robert , Xu Shixin , Huang Huaxiong
Published: January 2024

Voltage-gated K$_{\mathrm{v}}$ channels play fundamental roles in many biological processes, such as the generation of the action potential. The gating mechanism of K$_{\mathrm{v}}$ channels is characterized experimentally by single-channel recordings and ensemble properties of the channel currents. In this work, we propose a bubble model coupled with a Poisson–Nernst–Planck (PNP) system to capture the key characteristics, particularly the delay in the opening of channels. The coupled PNP system is solved numerically by a finite-difference method and the solution is compared with an analytical approximation. We hypothesize that the stochastic behaviour of the gating phenomenon is due to randomness of the bubble and channel sizes. The predicted ensemble average of the currents under various applied voltage across the channels is consistent with experimental observations, and the Cole–Moore delay is captured by varying the holding potential.
In Vivo Evolution of a Klebsiella pneumoniae Capsule Defect With wcaJ Mutation Promotes Complement-Mediated Opsonophagocytosis During Recurrent Infection
Authors: Bain William , Ahn Brian , Peñaloza Hernán F , McElheny Christi L , Tolman Nathanial , van der Geest Rick , Gonzalez-Ferrer Shekina , Chen Nathalie , An Xiaojing , Hosuru Ria , Tabary Mohammadreza , Papke Erin , Kohli Naina , Farooq Nauman , Bachman William , Olonisakin Tolani F , Xiong Zeyu , Griffith Marissa P , Sullivan Mara , Franks Jonathan , Mustapha Mustapha M , Iovleva Alina , Suber Tomeka , Shanks Robert Q , Ferreira Viviana P , Stolz Donna B , Van Tyne Daria , Doi Yohei , Lee Janet S
Published: January 2024

Background

Klebsiella pneumoniae carbapenemase–producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection.

Methods

We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model.

Results

We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice.

Conclusions

Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence.
Microbiome in a ground-based analog cabin of China Space Station during a 50-day human occupation
Authors: Zhang Ying , Li Zhidong , Peng Yuan , Guo Zimu , Wang Hong , Wei Tao , Shakir Yasmeen , Jiang Guohua , Deng Yulin
Published: January 2024

Dead-corner areas in space station that untouched by the clean-up campaign often experience microorganisms outbreaks, but the microbiome of these areas has never been studied. In this study, the microbiome in a ground-based analog ``Tianhe'' core module of China Space Station was first investigated during a 50-day three-crew occupation. Dead-corner areas were receiving attention by adopting a new sampling method. Results indicate that the astronauts occupation did not affect the dominant bacteria community, but affected a small proportion. Due to the frequent activity of astronauts in the work and sleep areas, the biomarkers in these two areas are common human skin surface and gut microorganisms, respectively. For areas that astronaut rarely visits, the biomarkers in which are common environmental microbial groups. Fluorescence counting showed that 70.12–84.78% of bacteria were alive, with a quantity of 104–105 cells/100 cm2. With the occupation time extension, the number of microorganisms increased. At the same sampling time, there was no significant bioburden difference in various locations. The cultivable bioburden ranged from 101 to 104 colony forming unit (CFU)/100 cm2, which are the following eight genera Penicillium, Microsphaeropsis, Stachybotrys, Humicola, Cladosporium, Bacillus, Planomicrobium, and Acinetobacter. Chryseomicrobium genus may be a key focus for future microbial prevention and control work.
Use of genotypic HIV DNA testing: a DELPHI-type consensus
Authors: Andre-Garnier Elisabeth , Bocket Laurence , Bourlet Thomas , Hocqueloux Laurent , Lepiller Quentin , Maillard Anne , Reigadas Sandrine , Barriere Guillaume , Durand François , Montes Brigitte , Stefic Karl , Marcelin Anne-Geneviève
Published: January 2024

Objectives

As many disparities in the clinical use of HIV DNA sequencing are observed, a DELPHI-type consensus was initiated in France to homogenize use, techniques and interpretation of results.

Methods

Based on a literature review and clinical experience, a steering committee (SC) of eight virologists and one infectious disease specialist formulated statements. Statements were submitted to an independent and anonymous electronic vote of virologists and HIV clinicians in France, between October 2022 and December 2022.

Results

The SC developed 20 statements grouped into six categories: clinical situations for the use of HIV DNA genotyping; techniques for performing HIV DNA genotyping; consideration of apolipoprotein B mRNA editing enzyme (APOBEC) mutations; genotyping results reporting; recycling of antiretrovirals; and availability of HIV DNA genotyping tests and delays. Twenty-one virologists and 47 clinicians participated in two voting rounds and 18/20 (90%) assertions reached a ‘strong’ consensus. For example, that prior genotyping on HIV DNA is useful for clinical decision-making when considering switching to some long-acting regimens or to reduce the number of antiretroviral agents in virologically suppressed patients for whom RNA data are unavailable/not exploitable/not sufficiently informative. Two statements achieved no consensus: reporting any detected viral minority population for discussion in multidisciplinary meetings (virologists), and possible risk of virological failure when using a second-generation InSTI plus lamivudine or emtricitabine regimen in patients with undetectable viral load within ≥1 year and in the presence of a documented M184V mutation within the last 5 years (clinicians).

Conclusions

This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing.