bluuebunny/crossref_metadata_2025 huggingface dataset:
Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism
Authors: Zanin-Zhorov Alexandra , Chen Wei , Moretti Julien , Nyuydzefe Melanie S. , Zhorov Iris , Munshi Rashmi , Ghosh Malavika , Serdjebi Cindy , MacDonald Kelli , Blazar Bruce R. , Palmer Melissa , Waksal Samuel D.
Published: November 2023

The pathogenesis of hepatic fibrosis is driven by dysregulated metabolism precipitated by chronic inflammation. Rho-associated coiled-coil-containing protein kinases (ROCKs) have been implicated in these processes, however the ability of selective ROCK2 inhibition to target simultaneously profibrotic, pro-inflammatory and metabolic pathways remains undocumented. Here we show that therapeutic administration of GV101, a selective ROCK2 inhibitor with more than 1000-fold selectivity over ROCK1, attenuates established liver fibrosis induced by thioacetamide (TAA) in combination with high-fat diet in mice. GV101 treatment significantly reduces collagen levels in liver, associated with downregulation of pCofilin, pSTAT3, pAkt, while pSTAT5 and pAMPK levels are increased in tissues of treated mice. In vitro, GV101 inhibits profibrogenic markers expression in fibroblasts, adipogenesis in primary adipocytes and TLR-induced cytokine secretion in innate immune cells via targeting of Akt-mTOR-S6K signaling axis, further uncovering the ROCK2-specific complex mechanism of action and therapeutic potential of highly selective ROCK2 inhibitors in liver fibrosis.
C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis
Authors: Goto Atsushi , Komura Shingo , Kato Koki , Maki Rie , Hirakawa Akihiro , Tomita Hiroyuki , Hirata Akihiro , Yamada Yasuhiro , Akiyama Haruhiko
Published: November 2023

Dupuytren’s contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren’s contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren’s contractures, we demonstrate that the activation of Wnt/β-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/β-catenin signalling are closely related to stromal cell–macrophage interactions, and Wnt/β-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-β-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell–macrophage interaction is a promising therapeutic target for Wnt/β-catenin-induced fibrosis.
Design and evaluation of tadpole-like conformational antimicrobial peptides
Authors: Tang Ziyi , Jiang Wuqiao , Li Shuangli , Huang Xue , Yang Yi , Chen Xiaorong , Qiu Jingyi , Xiao Chuyu , Xie Ying , Zhang Xu , Li Jianguo , Verma Chandra Shekhar , He Yun , Yang Aimin
Published: November 2023

Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of “tadpole-like” peptides consisting of an amphipathic α-helical head and an aromatic tail. A structure-activity relationship (SAR) study of “tadpole-like” temporin-SHf and its analogs revealed that increasing the number of aromatic residues in the tail, introducing Arg to the α-helical head and rearranging the peptide topology dramatically increased antimicrobial activity. Through progressive structural optimization, we obtained two peptides, HT2 and RI-HT2, which exhibited potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance. NMR and molecular dynamics simulations revealed that both peptides indeed adopted “tadpole-like” conformations. Fluorescence experiments and electron microscopy confirmed the membrane targeting mechanisms of the peptides. Our studies not only lead to the discovery of a series of ultrashort peptides with potent broad-spectrum antimicrobial activities, but also provide a new strategy for rational design of novel “tadpole-like” antimicrobial peptides.
Fe protein docking transduces conformational changes to MoFe nitrogenase active site in a nucleotide-dependent manner
Authors: Tokmina-Lukaszewska Monika , Huang Qi , Berry Luke , Kallas Hayden , Peters John W. , Seefeldt Lance C. , Raugei Simone , Bothner Brian
Published: November 2023

The reduction of dinitrogen to ammonia catalyzed by nitrogenase involves a complex series of events, including ATP hydrolysis, electron transfer, and activation of metal clusters for N2 reduction. Early evidence shows that an essential part of the mechanism involves transducing information between the nitrogenase component proteins through conformational dynamics. Here, millisecond time-resolved hydrogen-deuterium exchange mass spectrometry was used to unravel peptide-level protein motion on the time scale of catalysis of Mo-dependent nitrogenase from Azotobacter vinelandii. Normal mode analysis calculations complemented this data, providing insights into the specific signal transduction pathways that relay information across protein interfaces at distances spanning 100 Å. Together, these results show that conformational changes induced by protein docking are rapidly transduced to the active site, suggesting a specific mechanism for activating the metal cofactor in the enzyme active site.
Organic molecule-assisted intermediate adsorption for conversion of CO2 to CO by electrocatalysis
Authors: Zhang Kai , Wang Wenyuan , Wang Ying , Wang Wenhui , Wang Nanyang , Pu Jun , Li Qiulong , Yao Yagang
Published: November 2023

5-Mercapto-1-methylimidazole possesses the ability to coordinate with Zn and interact with the CO2 and intermediates, which helped to improve the CO2RR performance of Zn nanosheets.
Bimetallic nickel complexes containing imidazole-based phenolate ligands as efficient catalysts for the copolymerization of carbon dioxide with epoxides
Authors: Hsu Han-Fang , Liu Guan-Lin , Su Yu-Chia , Ko Bao-Tsan
Published: November 2023

In this study, a series of new structurally well-defined dinickel complexes containing imidazole-based diamine-bisphenolate ligands were found to effectively catalyze the ring-opening copolymerization (ROCOP) of CO2 and cyclohexene oxide.
Observation of inserted oxocarbonyl species in the tantalum cation-mediated activation of carbon dioxide dictated by two-state reactivity
Authors: Han Jia , Liu Pengcheng , Qiu Binglin , Wang Guanjun , Liu Shilin , Zhou Xiaoguo
Published: November 2023

The production of inserted oxocarbonyl species in the carbon dioxide activation by tantalum cations was identified using infrared photodissociation spectroscopy, where the oxygen atom transfer reactions are driven by two-state reactivity.
Direct synthesis of ultralight, elastic, high-temperature insulation N-doped TiO2 ceramic nanofibrous sponges via conjugate electrospinning
Authors: Cheng Wei , Jiao Wenling , Fei Yifan , Yang Zaihui , Zhang Xiaohua , Wu Fan , Liu Yitao , Yin Xia , Ding Bin
Published: November 2023

We report a low-cost, scalable strategy to fabricate N-doped TiO2 ceramic nanofibrous sponges with a continuous stratified structure by conjugate electrospinning.
Particle-in-cell simulations of electron–positron cyclotron maser forming pulsar radio zebras
Authors: Labaj Matúš , Benáček Jan , Karlický Marian
Published: November 2023

Context. The microwave radio dynamic spectra of the Crab pulsar interpulse contain fine structures represented via narrowband quasiharmonic stripes. The pattern significantly constrains any potential emission mechanism. Similar to the zebra patterns observed, for example, in type IV solar radio bursts or decameter and kilometer Jupiter radio emission, the double plasma resonance (DPR) effect of the cyclotron maser instability may allow for interpretion of observations of pulsar radio zebras.

Aims. We provide insight at kinetic microscales of the zebra structures in pulsar radio emissions originating close to or beyond the light cylinder.

Methods. We present electromagnetic relativistic particle-in-cell (PIC) simulations of the electron–positron cyclotron maser for cyclotron frequency smaller than the plasma frequency. In four distinct simulation cycles, we focused on the effects of varying the plasma parameters on the instability growth rate and saturation energy. The physical parameters were the ratio between the plasma and cyclotron frequency, the density ratio of the “hot” loss-cone to the “cold” background plasma, the loss-cone characteristic velocity, and comparison with electron–proton plasma.

Results. In contrast to the results obtained from electron–proton plasma simulations (for example, in solar system plasmas), we find that the pulsar electron–positron maser instability does not generate distinguishable X and Z modes. On the contrary, a singular electromagnetic XZ mode was generated in all studied configurations close to or above the plasma frequency. The highest instability growth rates were obtained for the simulations with integer plasma-to-cyclotron frequency ratios. The instability is most efficient for plasma with characteristic loss-cone velocity in the range vth = 0.2 − 0.3c. For low density ratios, the highest peak of the XZ mode is at double the frequency of the highest peak of the Bernstein modes, indicating that the radio emission is produced by a coalescence of two Bernstein modes with the same frequency and opposite wave numbers. Our estimate of the radiative flux generated from the simulation is up to ∼30 mJy from an area of 100 km2 for an observer at 1 kpc distance without the inclusion of relativistic beaming effects, which may account for multiple orders of magnitude.
Nine lensed quasars and quasar pairs discovered through spatially extended variability in Pan-STARRS
Authors: Dux Frédéric , Lemon Cameron , Courbin Frédéric , Neira Favio , Anguita Timo , Galan Aymeric , Kim Sam , Hempel Maren , Hempel Angela , Lachaume Régis
Published: November 2023

We present the proof of concept of a method for finding strongly lensed quasars using their spatially extended photometric variability through difference imaging in cadenced imaging survey data. We applied the method to Pan-STARRS, starting with an initial selection of 14 107 Gaia multiplets with quasar-like infrared colours from WISE. We identified 229 candidates showing notable spatially extended variability during the Pan-STARRS survey period. These include 20 known lenses and an additional 12 promising candidates for which we obtained long-slit spectroscopy follow-up. This process resulted in the confirmation of four doubly lensed quasars, four unclassified quasar pairs, and one projected quasar pair. Only three are pairs of stars or quasar+star projections. The false-positive rate accordingly is 25%. The lens separations are between 0.81″ and 1.24″, and the source redshifts lie between z = 1.47 and z = 2.46. Three of the unclassified quasar pairs are promising dual-quasar candidates with separations ranging from 6.6 to 9.3 kpc. We expect that this technique is a particularly efficient way to select lensed variables in the upcoming Rubin-LSST, which will be crucial given the expected limitations for spectroscopic follow-up.
A comparative study of two X2.2 and X9.3 solar flares observed with HARPS-N
Authors: Pietrow A. G. M. , Cretignier M. , Druett M. K. , Alvarado-Gómez J. D. , Hofmeister S. J. , Verma M. , Kamlah R. , Baratella M. , Amazo-Gómez E. M. , Kontogiannis I. , Dineva E. , Warmuth A. , Denker C. , Poppenhaeger K. , Andriienko O. , Dumusque X. , Löfdahl M. G.
Published: November 2023

Context.Stellar flares cannot be spatially resolved, which complicates ascertaining the physical processes behind particular spectral signatures. Due to their proximity to Earth, solar flares can serve as a stepping stone for understanding their stellar counterparts, especially when using a Sun-as-a-star instrument and in combination with spatially resolved observations.

Aims.We aim to understand the disk-integrated spectral behaviors of a confined X2.2 flare and its eruptive X9.3 successor, which had energies of 2.2 × 1031erg and 9.3 × 1031erg, respectively, as measured by Sun-as-a-star observations with the High Accuracy Radial velocity Planet Searcher for the Northern hemisphere (HARPS-N).

Methods.The behavior of multiple photospheric (NaD1&D2, Mg Iat 5173 Å, Fe Iat 6173 Å, and Mn Iat 4031 Å) and chromospheric (Ca IIH & K, Hα, Hβ, and He ID3) spectral lines were investigated by means of activity indices and contrast profiles. A number of different photospheric lines were also investigated by means of equivalent widths, and radial velocity measures, which were then related to physical processes directly observed in high-resolution observations made with the Swedish 1-m Solar Telescope (SST) and the Atmospheric Imaging Assembly (AIA) on board of the Solar Dynamics Observatory (SDO).

Results.Our findings suggest a relationship between the evolving shapes of contrast profile time and the flare locations, which assists in constraining flare locations in disk-integrated observations. In addition, an upward bias was found in flare statistics based on activity indices derived from the Ca IIH & K lines. In this case, much smaller flares cause a similar increase in the activity index as that produced by larger flares. Hα-based activity indices do not show this bias and are therefore less susceptible to activity jitter. Sodium line profiles show a strongly asymmetric response during flare activity, which is best captured with a newly defined asymmetrical sodium activity index. A strong flare response was detected in Mn Iline profiles, which is unexpected and calls for further exploration. Intensity increases in Hα, Hβ, and certain spectral windows of AIA before the flare onset suggest their potential use as short-term flare predictors.
Seven-year periodic variations in the methanol maser line displayed by the massive protostar IRAS 20216+4104
Authors: Szymczak M. , Durjasz M. , Goedhart S. , Wolak P. , Bartkiewicz A. , Caratti o Garatti A. , Kobak A. , Massi F.
Published: November 2023

Aims. We report the discovery and analysis of a periodic methanol maser in the massive protostar IRAS 20216+4104.

Methods. To obtain the light curve, we used the 6.7 GHz methanol maser spectra collected between 2000–2003 and 2009–2023 with the Hartebeesthoek and Torun radio telescopes, as well as spectra from the literature reported prior to 1992.

Results. The velocity-integrated flux density shows sinusoidal-like variations with a period of 6.9±0.03 yr. All but one of the features show periodic changes with a relative amplitude of 2 up to >89. A slightly variable feature displays a moderate anti-correlation between the flux density and the other significantly variable features. The maser emission appears to follow the continuum emission of the red-shifted outflow cavity. A maximum emission of 3.4 and 4.6 µm precedes the maser peak by 15% of the period and the (infrared) IR light centroids show time-dependent displacement. The periodic behaviour of the maser and IR emission is likely due to the eclipsing effect from a wobbling inner disk.
Optical circular polarization of blazar S4 0954+65 during high linear polarized states
Authors: Liodakis I. , Shablovinskaya E. , Blinov D. , Savchenko S. S. , Malygin E. , Kotov S. , Kiehlmann S. , Readhead A. C. S. , Potter S. B. , Rieger F. M. , Grishina T. S. , Hagen-Thorn V. A. , Kopatskaya E. N. , Larionova E. G. , Morozova D. A. , Troitskiy I. S. , Troitskaya Y. V. , Vasilyev A. A. , Zhovtan A. V. , Borman G. A.
Published: November 2023

Optical circular polarization observations can directly test the particle composition in black hole jets. We report the first observations of the BL Lac-type object S4 0954+65 in high linear polarized states. While no circular polarization was detected, we were able to place upper limits of < 0.5% at 99.7% confidence. Using a simple model and our novel optical circular polarization observations, we can constrain the allowed parameter space for the magnetic field strength and composition of the emitting particles. Our results favor models that require magnetic field strengths of only a few Gauss and models in which the jet composition is dominated by electron-positron pairs. We discuss our findings in the context of typical magnetic field strength requirements for blazar emission models.
Über Grenzen hinaus: erste Extrem-Langzeit-Impella-Unterstützung mit transkontinentaler Verlegung
Authors: Fitzner Sebastian , Fühner Thomas , Franke Andreas
Published: November 2023

Wir berichten über die erste transkontinentale Ambulanzjet-Verlegung eines 61-jährigen Patienten mit über 76 Tage liegender Impella CP-Pumpe nach kardiogenem Schock infolge eines akuten Myokardinfarkts. Nach initialer, diagnostischer Herzkatheteruntersuchung erfolgte, vor einer Hochrisiko-PCI, zunächst die Implantation einer IABP. 15 Tage später wurde auf eine Impella CP-Pumpe gewechselt, die nach 24 Tagen, aufgrund eines technischen Defekts, gewechselt werden musste. Seitdem befindet sich der Patient seit über 76 Tagen an einer Impella CP, was unserer Erkenntnis nach die weltweit längste dokumentierte Liegedauer ist. Aufgrund einer Kolonblutung unter der heparinversetzten Spülflüssigkeit der Impella und der DAPT musste die Antikoagulation mit Heparin gestoppt und stattdessen eine alternative Spüllösung mit Dextrose 5% und Natriumbicarbonat eingesetzt werden. Nach 3-monatigem stationären Aufenthalt erfolgte die Verlegung des Patienten aus den UAE in die USA zur Implantation
eines dauerhaften LVAD. Dies ist die erste Transkontinentalverlegung eines Impella-Patienten in einem Ambulanzjet mit einer Entfernung > 11000 km.
Progress of Polycyclic Boron-Doped Molecular Carbons
Authors: Yuan Liuzhong , Wang Yue , Dou Chuandong
Published: November 2023

Molecular carbons, namely molecular cutout of carbon materials, are of importance for understanding accurate structures of carbon allotropes and developing functional π-electron materials. Doping the boron atoms into π-conjugated skeletons of molecular carbons enables the construction of boron-doped molecular carbons (BMCs), further leading to new chemistry and attractive material systems, which are distinct from carbon-based and other heteroatom-doped molecular carbons. Herein, the bottom-up organic synthesis methodologies have been employed to synthesize BMCs that feature the boron atoms at the edge or in the center of π-skeletons. They have not only amazing topological structures and good stability but also intriguing photophysical and electronic properties. Moreover, they have sufficient Lewis acidity and can coordinate with Lewis bases to form Lewis acid–base complexes, which exhibit stimuli-responsive functions. Notably, some of these BMCs can be utilized in the fields of organic reactions, optical and electronic devices, as well as supramolecular chemistry and photothermal materials. In this short review, we aim to highlight the design and synthetic strategies of polycyclic BMCs, and their unique physical properties and practical applications.
Is There A Connection Between Primary Hypophysitis and Celiac
Disease?
Authors: Kara Zehra , Eşkazan Tuğçe , Şahin Serdar , Durcan Emre , Sulu Cem , Demir Ahmet Numan , Uysal Serhat , Özkaya Hande Mefkure , Yılmaz Erkan , Hatemi Ali İbrahim , Bolayırlı İbrahim Murat , Kadıoğlu Pınar
Published: November 2023

Aim To investigate the autoimmune and genetic relationship between primary
hypophysitis (PH) and celiac disease (CD).

Methods The study was retrospective and patients with PH followed in our
clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic,
pathologic, and radiologic findings and treatment modalities were assessed.
Patients diagnosed with CD in the Gastroenterology outpatient clinic in
2020–2022 were included in the study as a control group. Information
such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA)
DQ2/8 information, CD-specific antibody levels, pathologic results of
duodenal biopsy, treatment received, follow-up status, additional diseases,
hormone use, and surgical history was obtained from patient records at PH.

In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was
examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and
anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD
were measured.

Results The study included 19 patients with lymphocytic hypophysitis, 30
celiac patients, and 30 healthy controls. When patients diagnosed with
lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was
found in the pathologic findings. The detection rate of HLA-DQ2/8 was
80% in celiac patients and 42% in PH (p=0.044). (APA and
AAVP antibodies associated with PH were tested in two separate groups of
patients and in the control group. APA and anti-arginine vasopressin (AAVP)
levels in PH, CD and healthy controls, respectively M [IQR]: 542
[178–607];164 [125–243]; 82 [74–107] ng/dL
(p=0.001), 174 [52–218]; 60 [47–82]; 59 [48–76]
ng/dL (p=0.008) were detected. The presence of an
HLA-DQ2/8 haplotype correlates with posterior hypophysitis and
panhypophysitis (r=0.598, p=0.04 and r=0.657,
p=0.02, respectively).

Conclusion Although patients with PH were found to have significant levels
of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary
antibodies were detected in celiac patients compared with healthy controls, but
no hypophysitis clinic was observed at follow-up. Although these findings
suggest that the two diseases may share a common genetic and autoimmune basis,
the development of the disease may be partially explained by exposure to
environmental factors.
A bibliometric analysis of virtual influencers in the Web of Science
Authors: Vila-López Natalia , Kuster-Boluda Ines , Mora-Pérez Elisabet , Pascual-Riquelme Isabel
Published: November 2023

The role of virtual influencers has risen in popularity. However, the revisions on this are scarce and incomplete. In this framework, two main objectives guide this work: (i) to carry on a performance analysis to measure the visibility/impact of the scientific production on virtual influencers’ marketing (most cited authors, journals, and themes) and (ii) to visually present the scientific structure by topics of research in virtual influencers marketing as well as its evolution along time. A final set of 1740 papers about virtual influencer marketing was retrieved from the ISIWeb of Science (from 1997 to 2021). Three different periods of time were identified (i) from 1997 to 2012 (649 papers), (ii) from 2013 to 2016 (540 papers), and (iii) from 2017 to 2021 (514 papers). Our results have identified seven promising future research lines on this topic, highlighting the role of tourism and sports celebrities.
The survival and outcome of older patients with primary aneurysmal subarachnoid haemorrhage: a 2-year follow-up, multi-centre, observational study
Authors: Wang Bang-Yue , Peng Chao , Jiang Hong-Sheng , Yang Zhong-Hong , Zhao Yan , Song Yun-Fei , Li Jian , Yang Yi-Fan , Wang Zhen , Zhang Heng-Rui , Wu Zhuo-Lin , Cui Jian-Zhong , Yang Xin-Yu , Hu Fu-Guang
Published: November 2023

Background and Purpose

The management of older aneurysmal subarachnoid haemorrhage (aSAH) cases is a clinical challenge. This study aimed to analyse the survival and functional outcomes in older aSAH patients (age ≥ 70 years) to provide evidence for making treatment decisions for such patients.

Methods

We performed a 2-year follow-up analysis of the Chinese Multi-Centre Cerebral Aneurysm Database for older patients suffering from aSAH from 2017 to 2020. A survival analysis was used to investigate the mean survival and hazard ratios for death. Binary logarithmic regression was performed to investigate the odds ratio for independent survival and dependent survival.

Results

A total of 1,136 consecutive older patients with aSAH were assessed in this study, and 944 patients (83.1%) were followed up. The overall mean survival was 37.79 ± 1.04 months. A total of 380 (40.25%) patients died within 2 years after aSAH. In survival analysis, the predictors of mortality were older age, intracerebral haemorrhage (ICH) history, Hunt-Hess (H-H) grade, World Federation of Neurosurgical Societies (WFNS) grade and operative treatment decreased the risk of mortality compared to conservative treatment. In binary logarithmic regression, the predictors of dependent survival were hypertension, diabetes, WFNS grade.

Conclusions

The risk for 2-year mortality after aSAH increases markedly with older age, ICH history, H-H grade and WFNS grade. Risk factors for 2-year dependent survival were associated with hypertension, diabetes and WFNS grade in older patients with aSAH. Operative treatment markedly decreased mortality but did not significantly decrease the morbidity of dependent survival compared to conservative treatment.
We should be screening for benign paroxysmal positional vertigo (BPPV) in all older adults at risk of falling: a commentary on the World Falls Guidelines
Authors: Li Yuxiao , Smith Rebecca M , Whitney Susan L , Seemungal Barry M , Ellmers Toby J
Published: November 2023

Benign paroxysmal positional vertigo (BPPV) is amongst the commonest causes of dizziness and falls in older adults. Diagnosing and treating BPPV can reduce falls, and thereby reduce fall-related morbidity and mortality. Recent World Falls Guidelines recommend formal assessment for BPPV in older adults at risk of falling, but only if they report vertigo. However, this recommendation ignores the data that (i) many older adults with BPPV experience dizziness as vague unsteadiness (rather than vertigo), and (ii) others may experience no symptoms of dizziness at all. BPPV without vertigo is due to an impaired vestibular perception of self-motion, termed ‘vestibular agnosia’. Vestibular agnosia is found in ageing, neurodegeneration and traumatic brain injury, and results in dramatically increased missed BPPV diagnoses. Patients with BPPV without vertigo are typically the most vulnerable for negative outcomes associated with this disorder. We thus recommend simplifying the World Falls Guidelines: all older adults (>60 years) with objective or subjective balance problems, irrespective of symptomatic complaint, should have positional testing to examine for BPPV.
Do honest signals or piercing weapons determine rank in a polygynous ungulate?
Authors: Fattorini Niccolò , Tizzani Paolo , Dematteis Andrea , Lovari Sandro
Published: November 2023

In polygynous ungulates, males are often larger than females and bear more elaborate/larger weapons. Quantifying sexual dimorphism in different traits could provide insights into species-specific evolutionary pathways of sexual selection. Concerning the combination of secondary sexual traits, we found that Himalayan tahr (Hemitragus jemlahicus) is unique among the ~20 species in the tribe Caprini, as its body mass dimorphism is ~2-fold greater than the dimorphism in horn size, whereas horn shape appears to be near-monomorphic. Whilst horns show the same growth rate in both sexes, body mass increases faster in males. Considering age variation, dominant, golden-ruffed males are also heavier than brown-ruffed, lower-ranking males. Unlike most bovids, male–male competition in tahr does not seem to have influenced weapon development, suggesting a lower importance of horns in male–male competition compared to body mass, as their unritualized combat style also suggests. Our study highlights alternative evolutionary pathways occurring in the Caprinae, where intraspecific signals involve different traits, from weapons to pelage features. Accordingly, male tahr use their ruff colour as an ‘honest’ signal of rank.
Determining the core content of a digital survivorship care plan for melanoma survivors: a multistakeholder Delphi consensus study
Authors: Kamminga Nadia C W , Wakkee Marlies , Swart Inez , Nijsten Tamar E C , Lugtenberg Marjolein
Published: November 2023

Increasing melanoma incidence and improved survival emphasize the importance of survivorship care plans (SCPs). We conducted a multistakeholder Delphi study to achieve consensus on core melanoma SCP content. Of the 44 potential elements, 24 (55%) reached consensus for inclusion. Notably, melanoma survivors and healthcare providers differed in their preferences, with survivors prioritizing coordination improvements and healthcare providers emphasizing psychosocial care. Exploring and overcoming these differences in opinions and including the consented elements as a basis in the design of the SCP can facilitate its implementation in practice and lead to survivorship care tailored to stakeholders’ needs.
Formylpeptide receptor 1 contributes to epidermal barrier dysfunction-induced skin inflammation through NOD-like receptor C4-dependent keratinocyte activation
Authors: Shao Shuai , Sun Zhongbin , Chu Mengyang , Chen Jiaoling , Cao Tianyu , Swindell William R , Bai Yaxing , Li Qingyang , Ma Jingyi , Zhu Zhenlai , Schuler Andrew , Helfrich Yolanda , Billi Allison C , Li Zhiguo , Hao Junfeng , Xiao Chunying , Dang Erle , Gudjonsson Johann E , Wang Gang
Published: November 2023

Background

Skin barrier dysfunction may both initiate and aggravate skin inflammation. However, the mechanisms involved in the inflammation process remain largely unknown.

Objectives

We sought to determine how skin barrier dysfunction enhances skin inflammation and molecular mechanisms.

Methods

Skin barrier defect mice were established by tape stripping or topical use of acetone on wildtype mice, or filaggrin deficiency. RNA-Seq was employed to analyse the differentially expressed genes in mice with skin barrier defects. Primary human keratinocytes were transfected with formylpeptide receptor (FPR)1 or protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) small interfering RNA to examine the effects of these gene targets. The expressions of inflammasome NOD-like receptor (NLR)C4, epidermal barrier genes and inflammatory mediators were evaluated.

Results

Mechanical (tape stripping), chemical (acetone) or genetic (filaggrin deficiency) barrier disruption in mice amplified the expression of proinflammatory genes, with transcriptomic profiling revealing overexpression of formylpeptide receptor (Fpr1) in the epidermis. Treatment with the FPR1 agonist fMLP in keratinocytes upregulated the expression of the NLRC4 inflammasome and increased interleukin-1β secretion through modulation of ER stress via the PERK-eIF2α-C/EBP homologous protein pathway. The activation of the FPR1-NLRC4 axis was also observed in skin specimens from old healthy individuals with skin barrier defect or elderly mice. Conversely, topical administration with a FPR1 antagonist, or Nlrc4 silencing, led to the normalization of barrier dysfunction and alleviation of inflammatory skin responses in vivo.

Conclusions

In summary, our findings show that the FPR1-NLRC4 inflammasome axis is activated upon skin barrier disruption and may explain exaggerated inflammatory responses that are observed in disease states characterized by epidermal dysfunction. Pharmacological inhibition of FPR1 or NLRC4 represents a potential therapeutic target.
A O05 Global 30-day morbidity and mortality of surgery for perforated peptic ulcer – GRACE study
Authors: Abouelazayem Mohamed , Jain Rajesh , Wilson Michael , Martinino Alessandro , Balasubaramaniam Vignesh , Biffl Walter , Coccolini Federico , Riera Manel , Wadhawan Himanshu , Wazir Ishaan , Abderaouf Bettahar
Published: November 2023

Background

Perforated peptic ulcer (PPU) is a surgical emergency with a mortality rate of 16-30% and a morbidity rate of 20-50%. All studies reporting on the outcome of surgery for PPU are either local or national. Most of these are based on small cohort sizes. A few larger studies have been reported, but still limited to a single nation, accounting for the wide variations in the literature. There is a lack of global, multicenter data on this topic. We aimed to assess the global 30-day morbidity and mortality of surgery for PPU and the factors influencing it.

Methods

We conducted a global observational cohort study of patients who underwent surgery for PPU between 01/01/2022 and 30/06/2022. Adults (≥18 years) who underwent surgery for PPU and those who had a PPU in a bypassed stomach after bariatric surgery were included. We excluded patients with underlying gastric cancer, and those treated conservatively. Patients were divided into subgroups to study the influence of some variables. These were age (≤50 and >50 years), time from onset of symptoms to hospital presentation (≤24 and >24 hours), and surgical technique (open, laparoscopic, and laparoscopic converted to open).

Results

This is the first global study on this topic and included 1864 patients from 162 centers across 52 countries. Mean age was 49.7 ± 17 years, and males represented 78.3%. The mean hospital stay was 10 ± 9.2 days and the 30-day reoperation rate was 5.4%. The 30-day morbidity rate was 48.5% and mortality rate was 9.3%. On multivariate analysis, age >50 years, presentation >24 hours, female gender, shock on admission, and acute kidney injury were significantly associated with 30-day morbidity. 30-day mortality was significantly associated with age >50 years, female gender, acute kidney injury, and shock on admission.

Conclusions

Surgery for PPU carries high 30-day morbidity and mortality globally. Age > 50 years old, female gender, acute kidney injury, and signs of shock upon admission are independent factors that can increase the likelihood of 30-day mortality. Laparoscopic surgery appears to be underutilized despite lower morbidity and mortality rates.
BS O02 Pancreatic Exocrine Insufficiency after Bariatric Metabolic Surgery: Results from a Systematic Review and Meta-Analysis
Authors: Hall Lewis , Powell-Brett Sarah , Smith James Halle , Ward Liz , Wiggins Tom , Markar Sheraz , Roberts Keith
Published: November 2023

Background

Disruptive gastrointestinal symptoms and malnutrition are common following bariatric metabolic surgery (BMS), and pancreatic exocrine insufficiency (PEI) is a sparsely considered cause of such. Untreated PEI results in substantial patient harm and should be managed with pancreatic enzyme replacement therapy (PERT). The incidence of PEI, its diagnosis and management, is unclear after BMS. The aim of this review was to assimilate the literature on incidence, diagnosis, and management of PEI in patients following BMS.

Methods

A systematic review of PUBMED and Embase databases identified studies investigating PEI following BMS. A pooled analysis was performed to determine prevalence of PEI in each cohort, and benefit of PERT. Meta-analyses were performed using the software package Revman 5.4, in accordance with the recommendation of the Cochrane Collaboration.

Results

12 studies were included in the quantitative synthesis of PEI rate after BMS. The rate of PEI after any BMS was 23.0% (95% CI:14.6% - 32.6%) amongst 1157 patients, and most common after biliopancreatic diversion with duodenal switch (44.0% (95%CI: 9.2-82.1%)). The most common diagnostic test used was faecal-elastase-1 (FE-1) (10/12 studies) reporting <200 µg/g as diagnostic of PEI. Five studies considered management of PEI with 81.7% (95% CI: 73.8% - 88.6%) of patient’s responding positively to PERT when prescribed. One study specifically reported improved Vitamin D, quality of life and FE-1 following PERT, with no effect on weight loss.

Conclusions

PEI is common following BMS, particularly following bypass procedures, and may be a substantial contributor to post-operative malnutrition in these patients. With over 4/5th patients experiencing symptomatic benefit of PERT, and evidence suggesting it does not prohibit weight loss, future research must further illuminate the role of PERT in the post-operative story of BMS patients.
BS O05 Resource impacts of bariatric surgery emergencies on the NHS: a 5-year review from a regional bariatric centre
Authors: Alabdellat Osama Khaled , Nima Bara Abu , Alwani Omneya , Alkhaffaf Bilal
Published: November 2023

Background

Bariatric surgery is a safe and highly effective treatment for obesity. Whilst the risks of surgery are generally low, emergency presentations can be extremely challenging to manage, particularly in a cohort with complex health needs. In the UK, a large proportion of cases are undertaken outside of the NHS. Little is known about the burden that an indeterminate volume of elective cases has on a publicly funded healthcare system which may need to adapt to better care for this group. This study aimed to explore this topic further by understanding the changing trends of emergency care for bariatric surgery patients.

Methods

This was a retrospective review of all consecutive non-elective (NE) attendances and admissions between January 2018 and April 2023. The setting was a regional bariatric and metabolic surgery centre with a dedicated bariatric on-call service serving a regional population in the North-West of England. Patient demographics, data on index procedures, diagnostic and therapeutic interventions as well as length of hospital stay (LOS) and intensive therapy unit (ITU) stay was collected. Changing trends in presentations and resource utilization were explored.

Results

373 NE episodes resulted in 4311 bed day occupancy; 76% had privately funded surgery accounting for 66.5% of total bed days. Median LOS was 5 days (IQR 2-11). 29 episodes resulted in 176 ITU bed days (median 4 days). Band-related complications were the most frequent cause of episodes (167) versus gastric bypass (104) and gastric sleeve (88). Median time from index procedure was 5 years IQR (2-11). 397 fluoroscopies and 365 CT-scans were undertaken in addition to 270 interventions (186 surgical; 30 radiological; 26 bedside deflations and 28 endoscopic). There was a three-fold increase in episodes between 2021 and 2022.

Conclusions

Non-elective episodes related to bariatric surgery can occur many years after the index procedure and result in the use of significant diagnostic, therapeutic and system resource. Our results suggest that the landscape of emergency bariatric surgery is changing with more cases that result in greater complex management needs. Most NE episodes are a result of privately funded surgery (likely as a response to limited access in the NHS) which have contributed to this increased resource use. These changes have serious implications for service delivery and design in the NHS which needs to rapidly adapt to these needs.
BS O06 Robotic-assisted bariatric surgery: a systematic review on learning curves
Authors: Supparamaniam Shreyas , Supparamaniam Sandesh , Lim Jia-Jye , Lee Shiela , Kourounis Georgios
Published: November 2023

Background

Robotic-assisted minimally invasive surgery has improved patient outcomes and experiences in various surgical disciplines, demonstrating reduced complications, postoperative pain, and length of hospital stays. Within the field of bariatric surgery, the integration of robotic systems aims to further enhance patient outcomes compared to traditional laparoscopic procedures. However, the precise learning curve (LC) for robotic bariatric surgery has yet to be clearly defined. Considering this knowledge gap, our review aims to compile and analyse the most up-to-date evidence on LC outcomes in bariatric surgery procedures.

Methods

In this review, we searched PubMed, Embase, and Cochrane Central Library databases up to April 2023 to identify studies reporting LC outcomes for robotic bariatric procedures. The primary outcome was the number of operations required to reach LC stabilization. Secondary outcomes included surgeon characteristics, including the number of training surgeons, their prior laparoscopic and/or robotic experience, exposure to simulated robotic training and outcome measures, including complication rates, surgery duration, and length of stay. Our study is registered on PROSPERO (CRD42023425878), and no specific grants were received from funding agencies.

Results

Of 432 initial results, 18 articles were included. All were observational studies reporting 27 cohorts from 2006 to 2022, involving 2084 patients. There were one to four included surgeons. The overall median number of cases to overcome the LC was 35 (IQR 15-64). For gastric bypass (RGB), the median LC was 25 (IQR 15-69), while for sleeve gastrectomy (RSG), it was 31 (IQR 20-86). The overall operation time was 185 minutes (IQR 124-197), with RGB at 152 minutes (IQR 139-196) and RSG at 98 minutes (IQR 85-110). Five studies used the CUSUM methodology, while others lacked specified LC determination approaches.

Conclusions

Our review highlights that the learning curve for bariatric surgery can be navigated relatively quickly and safely. However, it also reveals that the existing evidence on learning curves for robotic bariatric surgery is derived from a limited number of surgeons with unclear levels of prior surgical experience. Furthermore, the heterogeneity in evaluating learning curves poses challenges for comprehensive analysis. Future studies should aim to outline differences in outcomes between established laparoscopic methods and robotic bariatric procedures, providing further clarity in this field.
HPB O01 HemopatchTM – A Viable Means of Preventing Post-Operative Pancreatic Fistula, A Multi-Institutional Review
Authors: Daoud Mohammed , Devine Michael , Naraine Urvashi , Abdelmoeti Mahmoud , O’Suilleabhain Criostoir , O’Sullivan Adrian
Published: November 2023

Background

Perioperative complications post distal pancreatectomy can be myriad. One of the most common is pancreatic fistula (POPF), with an incidence that can range widely. Many techniques are employed to prevent POPF but these are mainly equivocal.

Methods

We conducted a retrospective review of a prospectively maintained multi-institutional pancreatic resection database of patients who underwent surgery between 01/01/2018 and 31/12/2022. Cohorts were divided into those who had a HemopatchTM applied to the pancreatic stump and those without. Demographics, POPF Grade A and Grade B/C, peak drain amylase after day 3, complications, and 30-day mortality were analyzed. Statistical analysis was conducted using SPSS. Chi-squared and T-tests were employed with a p-value of <0.05 deemed significant.

Results

Demographics between the two groups were similar. Mucinous cystic neoplasms and pancreatic adenocarcinoma accounted for the majority of indications for resection. Through the use of HemopatchTM a statistically significant reduction in Grade A POPF was seen (39% vs 63%, p-value 0.04). Grade B/C POPF approached but did not reach statistical significance in difference (6% vs 18%, p-value 0.07). Peak drain amylase was 7989 IU/L in the cohort who did not have a Hemopatch applied while in the cohort who did there was a mean of 1818 IU/L (p-value 0.05).

Conclusions

The routine use of HemopatchTM is a safe adjunct in distal pancreatectomies. It renders a statistically significant reduction in Grade A POPF. For Grade B/C POPF it approaches but does not meet the threshold for significance. Routine use is advocated while larger prospective trials are undertaken.
OGBN O02 Ergonomics in laparoscopic cholecystectomy. Do we need to change our practice to look after ourselves?
Authors: Browning Matt , Johnson Courtney , Gore Megan , Alwis Anuradha , Soe Wunna , Walker Eleanor , Walmsley James , Chan David
Published: November 2023

Background

Up to 80% of surgeons report musculoskeletal problems which significantly affect their personal and professional lives. The cost of back pain alone in the NHS costs £400 million per year (for all staff), and surveyed surgeons report 40% have sustained an injury at work. Laparoscopic cholecystectomy is one of the most frequently performed surgical procedures but the musculoskeletal impact of this procedure on surgeons is unknown, though anecdotally it is likely to be high.

Methods

We observed the positions held by surgeons undertaking laparoscopic cholecystectomy and measured them against the Rapid Entire Body Assessment (REBA) score, which is widely used to assess the risk of an activity causing musculoskeletal injury. The higher the score, the less ergonomic the posture and the higher the risk of long term harm. Photographs were taken of the operating surgeon with consent (excluding views of the patient) and then measured against the score to assess the risk. Operations were graded to give an average risk score which represents the need for a change of process to safeguard staff.

Results

Eight laparoscopic cholecystectomies, undertaken by 6 different surgeons were analysed. Scores for trunk posture were generally low but score for upper limb position were higher. The mean and median REBA scores were both 4 and the maximum score during one operation was 6.

Conclusions

The scores measured in this small study were very consistent and suggest that the practice of laparoscopic cholecystectomy as currently practised has a medium risk of causing operator harm; practice change is recommended to safeguard staff. Further research is needed with larger sample sizes as well as different arms for techniques such as position changes or robotic surgery, while observing outcomes for patients and time taken.
OGBN O08 The Safety and Efficacy of Laparoscopic Hiatus Hernia Repair with Biosynthetic Mesh (Phasix-ST®): A Single Centre Experience
Authors: Quake Sharmaine Yen Ling , Peter Bennett , Munipalle Phanibhushana Chakravarthy , Viswanath Yirupaiahgari
Published: November 2023

Background

Surgical management of large hiatus hernia (> 5 cm defect) remains challenging due to high recurrence rates. Mesh augmentation in laparoscopic hiatal hernia repair has been used to reduce recurrences but carries risks such as mesh erosion, contraction, infection, and reaction to the foreign body. Introducing biosynthetic meshes offers a promising adjunct to primary suture repair of hiatal defects with enhanced tissue integration and reduced risk of infection. Phasix™ ST mesh is a biosynthetic mesh made of Poly-4-Hydroxybutyrate (P4HB). This study evaluates early patient outcomes following laparoscopic hiatal hernia repair with Phasix™ ST mesh, including its safety and efficacy profile.

Methods

This study was to evaluate outcomes of laparoscopic hiatus hernia repair using Phasix™ ST mesh in adult patients (>18 years) at our institution. All patients undergoing this procedure between September 2020 to April 2023 were identified from a prospectively maintained database. Our standardised technique involved on-lay crural reinforcement with Phasix™ ST mesh after primary closure of the hiatal defect, followed by partial fundoplication. Patient records were reviewed retrospectively to assess these end-point measures: postoperative mortality and morbidity at 30 days, functional results reported during the follow-up period, and recurrence rates of hiatus hernia.

Results

Conclusions

This is the first study in the United Kingdom demonstrating that laparoscopic hiatus hernia repair with the use of Phasix™ ST mesh for crural reinforcement has low-rate complications, with most patients reporting symptom improvement and discontinuing PPI use in the early-term follow–up. Further long-term studies are needed to validate these findings.