bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Step-Up Dual Endoscopic Approach for Large-Size Infected Pancreatic Necrosis: Percutaneous Endoscopic Necrosectomy Followed by Transluminal Endoscopic Drainage/Necrosectomy
Authors: Mangiafico Santi , Bertani Helga , Pigò Flavia , Russo Salvatore , Lupo Marinella , Cocca Silvia , Grande Giuseppe , Germani Ugo , Manta Raffaele , Conigliaro Rita 
Published: February 2024

Background:
Acute pancreatitis in 10% to 20% of cases can be associated with necrosis of the pancreatic gland, peripancreatic tissue, or both. We report a case series of a new endoscopic approach to treat infected pancreatic necrosis (IPN).

Patients and Methods:
Consecutive patients with IPN, extending from the perigastric area up to the paracolic gutters or into the pelvis, were prospectively studied from January 2017 to June 2022. The treatment protocol was radiologic percutaneous drainage as the first step, followed by fully covered metal stent placement (FC-SEMS) in the track of the catheter. Percutaneous endoscopic necrosectomy (PEN) was performed 2 to 4 days later using a flexible endoscope through the percutaneous tract. About 2 to 4 weeks later, when a matured sac was visible, EUS-guided endoscopic transluminal drainage (ETD) with lumen-apposing metal stents (LAMS) was performed. Control of sepsis with resolution of collection(s) was the primary outcome measure.

Results:
We included 18 patients, males in 50% of cases with age 60±12 years old. Most frequent cause of pancreatitis was biliary (7 cases) followed by alcoholic in 6 cases; in 3 cases pancreatitis was caused by hyperlipemia and in 2 cases was idiopathic. Mean size of WON was 18±2 cm. For PEN, SEMSs used were esophageal FC-SEMS. LAMS used for ETD were Hot Axios, Hot Spaxus and Nagistent. Mean time of endoscopic intervention for PEN and ETD was 18±3 and 37±4 days, respectively. In 5 cases adverse events occurred: 3 cases of overinflations resolved with introduction of Verres needles in abdomen. In 2 cases postprocedural GI bleeding required endoscopic intervention. In all cases control of sepsis was reached together with resolution of collections. No cases of deaths were observed.

Conclusions:
Step-up percutaneous and transluminal endoscopic necrosectomy therapy is an effective strategy for large-size IPN with combined central and peripheral necrosis.
Invasive Fungal Infections in Inpatient Solid Organ Transplant Recipients With COVID-19: A Multicenter Retrospective Cohort
Authors: Permpalung Nitipong , Chiang Teresa Po-Yu , Manothummetha Kasama , Ostrander Darin , Datta Kausik , Segev Dorry L. , Durand Christine M. , Mostafa Heba H. , Zhang Sean X. , Massie Allan B. , Marr Kieren A. , Avery Robin K. 
Published: February 2024

Background.
The prevalence and outcomes of COVID-19-associated invasive fungal infections (CAIFIs) in solid organ transplant recipients (SOTRs) remain poorly understood.

Methods.
A retrospective cohort study of SOTRs with COVID-19 admitted to 5 hospitals within Johns Hopkins Medicine was performed between March 2020 and March 2022. Cox regression multilevel mixed-effects ordinal logistic regression was used.

Results.
In the cohort of 276 SOTRs, 22 (8%) developed IFIs. The prevalence of CAIFIs was highest in lung transplant recipients (20%), followed by recipients of heart (2/28; 7.1%), liver (3/46; 6.5%), and kidney (7/149; 4.7%) transplants. In the overall cohort, only 42 of 276 SOTRs (15.2%) required mechanical ventilation; these included 11 of 22 SOTRs (50%) of the CAIFI group and 31 of 254 SOTRs (12.2%) of the no-CAIFI group. Compared with those without IFIs, SOTs with IFIs had worse outcomes and required more advanced life support (high-flow oxygen, vasopressor, and dialysis). SOTRs with CAIFIs had higher 1-y death-censored allograft failure (hazard ratio 1.65.116.4, P = 0.006) and 1-y mortality adjusting for oxygen requirement (adjusted hazard ratio 1.12.45.1, P < 0.001), compared with SOTRs without CAIFIs.

Conclusions.
The prevalence of CAIFIs in inpatient SOTRs with COVID-19 is substantial. Clinicians should be alert to the possibility of CAIFIs in SOTRs with COVID-19, particularly those requiring supplemental oxygen, regardless of their intubation status.
Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women
Authors: Becker Erica C. , Siddique Osama , O’Sullivan David M. , Dar Wasim , Einstein Michael , Morgan Glyn , Emmanuel Bishoy , Sotil Eva U. , Richardson Elizabeth , Serrano Oscar K. 
Published: February 2024

Background.
Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort.

Methods.
We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis.

Results.
During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P < 0.001) than White women and non-White male patients (26.1 versus 24.8; P < 0.001). Graft and patient survivals were significantly different (P < 0.001) between non-White women and White women and men (White and non-White).

Conclusions.
Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.
First-in-human Study With LIS1, a Next-generation Porcine Low Immunogenicity Antilymphocyte Immunoglobulin in Kidney Transplantation
Authors: Viklicky Ondrej , Slatinska Janka , Janousek Libor , Rousse Juliette , Royer Pierre-Joseph , Toutain Pierre-Louis , Cozzi Emanuele , Galli Cesare , Evanno Gwenaelle , Duvaux Odile , Bach Jean-Marie , Soulillou Jean-Paul , Giral Magali , Vanhove Bernard , Blancho Gilles 
Published: February 2024

Background.
Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti-N-glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models.

Methods.
This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg.

Results.
CD3+ T cell depletion <100/mm3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2–4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected.

Conclusions.
In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.
Efficient Generation of Protein Pockets with PocketGen
Authors: Zhang Zaixi , Shen Wan Xiang , Liu Qi , Zitnik Marinka 
Published: February 2024

AbstractDesigning protein-binding proteins is critical for drug discovery. However, the AI-based design of such proteins is challenging due to the complexity of ligand-protein interactions, the flexibility of ligand molecules and amino acid side chains, and sequence-structure dependencies. We introduce PocketGen, a deep generative model that simultaneously produces both the residue sequence and atomic structure of the protein regions where ligand interactions occur. PocketGen ensures consistency between sequence and structure by using a graph transformer for structural encoding and a sequence refinement module based on a protein language model. The bilevel graph transformer captures interactions at multiple scales, including atom, residue, and ligand levels. To enhance sequence refinement, PocketGen integrates a structural adapter into the protein language model, ensuring that structure-based predictions align with sequence-based predictions. PocketGen can generate high-fidelity protein pockets with superior binding affinity and structural validity. It operates ten times faster than physics-based methods and achieves a 95% success rate, defined as the percentage of generated pockets with higher binding affinity than reference pockets. Additionally, it attains an amino acid recovery rate exceeding 64%.
A method for correcting systematic error in PO2measurement to improve measures of oxygen supply capacity
Authors: Timpe A.W. , Seibel B.A 
Published: February 2024

AbstractAn organism’s oxygen supply capacity (α) can be measured as a ratio of the metabolic rate (MR) and the critical oxygen partial pressure (Pc). However, this metric is sensitive to errors in the measurement of PO2, especially at low PO2where the ratio of instrument error to environmental oxygen is magnified. Consequently, the oxygen supply capacity of animals, particularly those that evolved in low-oxygen environments, may appear unnaturally high and variable. Here, we present a method to correct for instrumental calibration error and use simulated and literature datasets to demonstrate how it can be usedpost hocto diagnose error in, correct the magnitude of, and reduce the variability in repeat measures of the oxygen supply capacity.
Metaplastic neuromodulation via transcranial direct current stimulation has no effect on corticospinal excitability and neuromuscular fatigue
Authors: Boda Madison R , Otieno Lavender A , Smith Ashleigh E , Goldsworthy Mitchell R , Sidhu Simranjit K 
Published: February 2024

ABSTRACTTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra– and inter-individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate fatigue. 15 young healthy adults (6 males, 22 ± 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 minutes. Fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate fatigue in young healthy individuals.
Helical grooves on the surfaces of microtrichia in European Hornets: Functional significance for antipodal relation between right and left hindwings
Authors: Inoué Sayako , Sato Hisako , Yamagishi Akihiko 
Published: February 2024

AbstractThe surface structures of microtrichia on the hindwings ofVerspa Crabro(European hornets) were observed by scanning electron microscopy (SEM). Helical grooves were seen in the microtrichia on both the ventral and dorsal sides. Their helical orientation varied spatially across the wing surface but were the same in the ventral and dorsal surfaces. Notably the grooves wound antipodally between the left and right wings. The observed chirality relation might be related to the effective anti-wetting of hindwings. The results demonstrated the importance of microscopic chirality in understrading the functions of insect wings.
Supplementary motor area disinhibition during motor sequence learning: A TMS-EEG study
Authors: Thong Sophie , Doery Elizabeth , Biabani Mana , Rogasch Nigel C. , Chong Trevor T. -J. , Hendrikse Joshua , Coxon James P. 
Published: February 2024

AbstractBackgroundIn primary motor cortex, changes in excitatory and inhibitory neurotransmission (E:I balance) accompany motor sequence learning. In particular, there is an early reduction in inhibition (i.e., disinhibition). The supplementary motor area (SMA) is a key brain region involved in the learning of sequences, however the neurophysiological mechanisms within SMA which support motor sequence learning remain poorly understood. Disinhibition may also occur in SMA, but this possibility remains unexamined.ObjectiveWe investigated disinhibition within SMA during motor sequence learning using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG).MethodsTwenty-nine healthy adults practiced a sequential motor task. TMS-evoked potentials (TEPs) resulting from SMA stimulation were measured with EEG before, during, and after practice. The N45 TEP peak was our primary measure of disinhibition. Furthermore, the slope of aperiodic EEG activity was included as an additional E:I balance measure.ResultsSignificant improvements in task performance (i.e., learning) occurred with practice. We observed smaller N45 amplitudes during early learning relative to baseline (bothp< .01), indicative of disinhibition. Intriguingly, aperiodic exponents increased as learning progressed and were associated with greater sequence learning (p< .05).ConclusionOur results show disinhibition within SMA during the planning phase of motor sequence learning and thus provide novel understanding on the neurophysiological mechanisms within higher-order motor cortex that accompany new sequence learning.
Components of Mnemonic Metacognition Constitutionally Supported by High Gamma Activity Between the Precuneus and Hippocampus
Authors: Pan Kai , Guo Xinxia , Zheng Zhe , Zhu Zhoule , Wu Hemmings , Zhu Junming , Ye Hongyi , Cai Yudian , Santos-Pata Diogo , Zhang Jianmin , Kwok Sze Chai , Jiang Hongjie 
Published: February 2024

ABSTRACTMetacognition, the ability to introspectively monitor one’s own performance, remains an area with poorly understood neural mechanisms, particularly regarding the intercommunication among various brain regions. Recent studies have identified the precuneus as a key region in mnemonic metacognitive tasks, while the hippocampus is recognized for its role in memory function. This study aimed to investigate the role of the precuneus and hippocampus in mnemonic metacognition by utilizing intracranial electrode recordings from patients with intractable epilepsy to analyze the correlational dynamics between these regions. Our findings revealed that high gamma activity serve as a key feature in both the precuneus and hippocampus for confidence judgment. Based on signal detection theory (SDT), we discovered that high gamma activity in the precuneus is significantly linked to type 2 sensitivity (meta-d’), while hippocampal high gamma activity was primarily linked to type 1 sensitivity (d’). Additionally, the correlation between high gamma activity in the hippocampus and precuneus was exclusively related to type 2 sensitivity (meta-d’). Temporal analysis indicated that the hippocampus is initially engaged for the memory process, followed by its joint engagement together with the precuneus for confidence generation. These findings elucidate the distinct electrophysiological roles of the hippocampus and precuneus in mnemonic metacognition, providing deeper insights into the neural mechanisms underlying this cognitive process.
mRNA-delivered consensus allergens induce a neutralizing IgG response against food and pollen allergens
Authors: Møiniche Mark , Johansen Kristoffer H. , Parrón-Ballesteros Jorge , Corneliussen Josefine K. , Eriksen Helena Højsted , Kringelum Jens Vindahl , Hadrup Sine Reker , Luengo Olga , Cardona Victoria , Bartra Joan , Pascal Mariona , Turnay Javier , Villalba Mayte , Münter Rasmus , Jenkins Timothy P. , Laustsen Andreas H. , Rivera-de-Torre Esperanza 
Published: February 2024

AbstractPollen-food allergy syndrome (PFAS) affects a significant proportion of the global population with a major health and socioeconomic impact. Patients are generally treated against the major sensitized allergen which does not warrant protection against cross-reactive allergens, leading to long and ineffective treatment regimens. For food allergies, patient guidelines rely on source avoidance, leading to dietary restrictions and reduced quality of life - in particular for those suffering from PFAS. To overcome these limitations, we introduce a novel allergy immunotherapy (AIT) approach utilizing consensus allergens and mRNA technology to achieve broader, safer, and faster desensitization in PFAS patients. We first designed a consensus allergen of orthologs of non-specific Lipid Transfer Proteins (cnsLTP-1) representing a broad spectrum of nsLTP allergens prevalent in food and pollen sources. CnsLTP-1 was delivered to naïve BALB/c mice using mRNA-lipid nanoparticles (mRNA-LNP) as vehicle, or by a traditional protein formulation, to assess if it elicits broad protection against allergens from different sources. Immunization with both mRNA-LNP and protein formulations demonstrated that cnsLTP-1-specific IgGs could be induced, whilst the mRNA-LNP formulation notably avoided the induction of allergen-specific IgEs. The induced antibodies were capable of recognizing and binding to a variety of nsLTPs, and effectively blocked the binding of allergens by allergic patient serum IgEs. This study thus demonstrates that the presented AIT strategy, based on mRNA-LNP technology and consensus allergens, could find clinical utility by addressing the limitations of current AIT. Further development of this technology platform could pave the way for more effective and patient-friendly treatments for PFAS and other cross-reactive allergies.
Evidence for a trade-off between glyphosate resistance and anti-grazer defence in green algaChlamydomonas reinhardtii
Authors: Hansson Erika M , Childs Dylan Z , Beckerman Andrew P 
Published: February 2024

ABSTRACTThe widespread and persistent use of herbicides has both selected for dramatically increased levels of herbicide resistance in the weed populations they were designed to control, and increased contamination of non-target ecosystems.Experimental evolution using microbes offers the opportunity to explore basic evolutionary theory, including testing for the existence of intrinsic and extrinsic fitness trade-offs, connecting them to the patterns observed in both natural and agricultural populations.We used green algaChlamydomonas reinhardtiiadapted to high and moderate levels of glyphosate to test for an extrinsic cost to glyphosate resistance in the form of a trade-off with clumping, the inducible anti-grazer defence deployed against gape-limited micrograzers. Through exposing the algae to freshwater rotiferBrachionus calyciflorusas well as their isolated info-chemicals, we test whether glyphosate resistance affects ability to deploy defences as well as ability to withstand grazing compared to control populations.We find an increase in variation rather than uni-directional effect of glyphosate treatment, with treated populations exhibiting both lower and higher degree of anti-grazer defence compared to controls. Furthermore, our data suggests there are at least three different glyphosate resistant phenotypes present, with two conferring different extrinsic costs in the form of tradeoff with anti-grazer defence.Our study indicates that extrinsic costs to glyphosate resistance may be context dependent in this system, possibly only being present at particular stages in the adaptation process or with particular resistance mechanisms.
ADAMTS7 promotes smooth muscle foam cell expansion in atherosclerosis
Authors: Chung Allen , Chang Hyun K. , Pan Huize , Bashore Alexander C. , Shuck Karissa , Matias Caio V. , Gomez Juliana , Yan Hanying , Li Mingyao , Bauer Robert C. 
Published: February 2024

ABSTRACTHuman genetic studies have repeatedly associatedADAMTS7with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic and induced in response to vascular injury and that the proatherogenicity of ADAMTS7, a secreted protein, is due to its catalytic activity. However, the cell-specific mechanisms governing ADAMTS7 proatherogenicity remain unclear. To determine which vascular cell types expressADAMTS7, we interrogated single-cell RNA sequencing of human carotid atherosclerosis and foundADAMTS7expression in smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts. We subsequently created SMC- and EC-specificAdamts7conditional knockout and transgenic mice. Conditional knockout ofAdamts7in either cell type is insufficient to reduce atherosclerosis, whereas transgenic induction in either cell type increases atherosclerosis. In SMC transgenic mice, this increase coincides with an expansion of lipid-laden SMC foam cells and decreased fibrous cap formation. RNA-sequencing in SMCs revealed an upregulation of lipid uptake genes typically assigned to macrophages. Subsequent experiments demonstrated that ADAMTS7 increases SMC oxLDL uptake through increased CD36 levels. Furthermore,Cd36expression is increased due to increased levels of PU.1, a transcription factor typically associated with myeloid fate determination. In summary,Adamts7expression in either SMCs or ECs promotes SMC foam cell formation and atherosclerosis. In SMCs, ADAMTS7 promotes oxLDL uptake via increased PU.1 andCd36expression, thereby increasing SMC foam cell formation and atherosclerosis.