bluuebunny/crossref_metadata_2025_split huggingface dataset:
20 Years of Abdominal Wall Allotransplantation - A Systematic Review of the Short and Long-Term Outcomes with a View to Future Modifications
Authors: Reed Laura T. , Echternacht Scott R. , Shanmugarajah Kumaran , Hernandez Roberto , Langstein Howard N. , Leckenby Jonathan I. 
Published: September 2022

Background:
Abdominal wall allotransplant (AWA) following intestinal and multivisceral transplant procedures has proven to be successful in achieving adequate closure in patients where other techniques have proven inadequate. Thus far, the focus of these AWAs has been on graft and overall patient survival following surgery and the implementation of immunosuppression.

Objectives:
The purpose of this study is to review the outcomes of AWA reported in the literature.

Data Sources:
The PubMed database was queried, and 2595 articles were found. Search criteria used were “abdominal wall transplant” and “abdominal wall allotransplant.” Of these, 8 met inclusion/exclusion criteria.

Results:
In the present study, 8 publications were identified reporting AWAs, for a total of 38 full-thickness AWAs done worldwide. All studies reported AWA in combination with visceral organ allotransplantation (VOA). AWAs reported thus far have been non-neurotized.

Discussion:
AWAs have proven to be beneficial both in terms of abdominal wall closure as well as acting as a sentinel marker for rejection for underlying VOAs. The success of AWAs and their long-term survival has introduced the question of functionality and long-term durability. Cadaveric studies have shown it is possible to neurotize AWAs, and future direction toward neurotized AWAs requires tools to assess functional outcomes of these transplants.

Conclusions and Implications:
AWA is an important reconstructive option when abdominal wall closure is challenging and should be considered in combination with VOAs. There may be potential benefit in neurotizing the AWA for functional use, and future studies should aim to include functional outcomes.
Update on pathogenesis, management, and control of Plasmodium vivax
Authors: Khan Nazia , Daily Johanna P. 
Published: September 2022

Purpose of review
This is a review of Plasmodium vivax epidemiology, pathogenesis, disease presentation, treatment and innovations in control and elimination. Here, we examine the recent literature and summarize new advances and ongoing challenges in the management of P. vivax.

Recent findings

P. vivax has a complex life cycle in the human host which impacts disease severity and treatment regimens. There is increasing data for the presence of cryptic reservoirs in the spleen and bone marrow which may contribute to chronic vivax infections and possibly disease severity. Methods to map the geospatial epidemiology of P. vivax chloroquine resistance are advancing, and they will inform local treatment guidelines. P. vivax treatment requires an 8-aminoquinoline to eradicate the dormant liver stage. Evidence suggests that higher doses of 8-aminoquinolines may be needed for radical cure of tropical frequent-relapsing strains.

Summary

P. vivax is a significant global health problem. There have been recent developments in understanding the complexity of P. vivax biology and optimization of antimalarial therapy. Studies toward the development of best practices for P. vivax control and elimination programs are ongoing.
An Ectopic Parathyroid Adenoma Mimicking Submandibular Gland on 99mTc-MIBI Parathyroid Scintigraphy
Authors: Chen Meijie , Chen Song , Li Xuena , Li Yaming 
Published: September 2022

Abstract
A 67-year-old woman complained of continuous low back pain for 4 months. She was referred for a 99mTc-MIBI parathyroid scintigraphy with neck SPECT/CT imaging. The planar images showed no abnormal uptake. However, on the SPECT/CT scan, a soft tissue nodule with high uptake was noted adjacent to the left submandibular gland, mimicking normal submandibular gland uptake. Pathological examination from surgical specimen showed that it was an ectopic parathyroid adenoma.
Optimal Timing of Perioperative Chemoprophylaxis in Patients With High Thromboembolic Risk Undergoing Major Abdominal Surgery
Authors: Liu David S. , Stevens Sean G. , Watson David I. , Goh Su Kah , Muralidharan Vijayaragavan , Wong Enoch , Fong Jonathan , Wong Darren J. ,   PROTECTinG Investigators,   VERITAS Collaborative
Published: September 2022

Objective:
To determine whether early (before skin closure) versus postoperative chemoprophylaxis affects the incidence of venous thromboembolism (VTE) and bleeding following major abdominal surgery, in a high thromboembolic risk population.

Background:
Major abdominal surgery incurs both VTE and bleeding risks. Patients with high preoperative VTE risk derive the most benefit from chemoprophylaxis, but carry an increased risk of bleeding. The optimal window for chemoprophylaxis in the perioperative period, whereby both VTE and bleeding risks are minimized, is unknown.

Methods:
Analysis of pooled data from 5 multicenter studies including only high thromboembolic risk (Caprini score >4) patients. Clinical VTE was defined as radiographically proven symptomatic disease <30 days postsurgery. Major bleeding was defined as the need for blood transfusion, reintervention, or >20 g/L fall in hemoglobin.

Results:
From 5501 cases, chemoprophylaxis was initiated early in 1752 (31.8%) patients and postoperatively in 3749 (68.2%) patients. Baseline characteristics were similar between study groups. The incidence of clinical VTE was not associated with chemoprophylaxis timing [early 0.7% vs. postop 0.7%, odds ratio (OR): 1.11, 95% confidence interval (CI): 0.60–2.15, P=0.730]. Contrastingly, compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (5.1% vs. 2.6%, OR: 2.04, 95% CI: 1.52–2.73, P<0.001) major bleeding (3.6% vs. 1.8%, OR: 1.99, 95% CI: 1.40–2.81, P<0.001), and reintervention (2.0% vs. 1.0%, OR: 2.10, 95% CI: 1.32–3.35, P=0.003). Early chemoprophylaxis independently predicted postoperative bleeding (OR: 1.71, 95% CI: 1.25–2.34, P<0.001), but not VTE.

Conclusions:
In high VTE risk patients undergoing major abdominal surgery, chemoprophylaxis commenced postoperatively reduces bleeding risk without affecting clinical VTE risk.
Differential kinetic analysis using nucleotide recoding RNA-seq and bakR
Authors: Vock Isaac W. , Simon Matthew D. 
Published: September 2022

AbstractConventional RNA sequencing (RNA-seq) provides limited information about the kinetic mechanisms underlying changes in RNA levels. Nucleotide recoding RNA-seq methods (NR-seq; e.g., TimeLapse-seq, SLAM-seq, etc.) are widely used approaches to identify changes in RNA synthesis and degradation kinetics, yet no software exists to rigorously compare the parameters of RNA kinetics between experimental conditions. We developed bakR to address this need. bakR relies on Bayesian hierarchical modeling of NR-seq data to increase statistical power by sharing information across transcripts. Using simulated and real data, we validate bakR and demonstrate how it provides new insights into the kinetics of RNA metabolism.
The UIP honeycomb airway cells are the site of mucin biogenesis with deranged cilia
Authors: Herrera Jeremy A. , Dingle Lewis A. , Montero M. Angeles , Venkateswaran Rajamiyer V. , Blaikley John F. , Granato Felice , Pearson Stella , Lawless Craig , Thornton David J. 
Published: September 2022

AbstractHoneycombing (HC) is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). HC refers to cystic airways (HC airways) located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic HC airway cells and fibrotic uninvolved airway cells (distant from sites of UIP and morphologically intact) in 10 UIP specimens; 6 non-fibrotic airway cell specimens served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 UIP and 6 mucinous adenocarcinoma (MA) specimens. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to HC airway cells, showing deregulation of SLITs and ROBO pathway as the strongest category. We find that BPIFB1 is the most significantly increased secretome-associated protein in UIP, whereas MUC5AC is the most significantly increased in MA. We conclude that spatial proteomics demonstrates that the fibrotic uninvolved airway cells are abnormal. In addition, fibrotic HC airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach will generate novel and testable hypotheses to decipher fibrosis progression.
Random Tactile Noise Stimulation Reveals Beta-Rhythmic Impulse Response Function of the Somatosensory System
Authors: Chota Samson , VanRullen Rufin , Gulbinaite Rasa 
Published: September 2022

AbstractBoth passive tactile stimulation and motor actions result in dynamic changes in beta-band (15-30 Hz Hz) oscillations over somatosensory cortex. Similar to alpha-band (8-12 Hz) power decrease in the visual system, beta-band power also decreases following stimulation of the somatosensory system. This relative suppression of alpha and beta oscillations is generally interpreted as an increase in cortical excitability. Here, next to traditional single-pulse stimuli, we employed a random intensity continuous right index finger tactile stimulation (white noise), which enabled us to uncover an impulse response function (IRF) of the somatosensory system. Contrary to previous findings, we demonstrate a burst-like initial increase rather than decrease of beta activity following white noise stimulation (human participants, N = 18, 8 female). These beta bursts, on average, lasted for 3 cycles and their frequency was correlated with resonant frequency of somatosensory cortex, as measured by a multi-frequency steady-state somatosensory evoked potential (SSSEP) paradigm. Furthermore, beta-band bursts shared spectro-temporal characteristics with evoked and resting-state beta oscillations. Taken together, our findings not only reveal a novel oscillatory signature of somatosensory processing that mimics the previously reported visual IRFs, but also point to a common oscillatory generator underlying spontaneous beta bursts in the absence of tactile stimulation and phase-locked beta bursts following stimulation, the frequency of which is determined by the resonance properties of the somatosensory system.Significance StatementThe investigation of the transient nature of oscillations has gained great popularity in recent years. The findings of bursting activity rather than sustained oscillations in the beta-band has provided important insights into its role in movement planning, working memory, inhibition and reactivation of neural ensembles. In this study, we show that also in response to tactile stimulation the somatosensory system responds with ∼3 cycle oscillatory beta-band bursts, whose spectro-temporal characteristics are shared with evoked and resting-state beta-band oscillatory signatures of the somatosensory system. As similar bursts have been observed in the visual domain, these oscillatory signatures might reflect an important supramodal mechanism in sensory processing.
Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis: three case studies
Authors: Fujino Akihiro , Fuchimoto Yasushi , Mori Teizaburo , Kano Motohiro , Yamada Yohei , Ohno Michinobu , Baba Yoshiyuki , Isogawa Nobutaka , Arai Katsuhiro , Yoshioka Takako , Abe Makoto , Kanai Nobuo , Takagi Ryo , Maeda Masanori , Umezawa Akihiro 
Published: September 2022

AbstractBackgroundWe performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis (CES) were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy.MethodsEpithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations.ResultsSubject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subject 2 did not require EBD for more than 18 months after transplantation, and Subject 3 did not require EBD for at least 9 months after transplantation, during which time they were able to maintain a normal diet by mouth.ConclusionsSubject 2 was free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis.Trial registrationUMIN, UMIN000034566, registered 19 October 2018,https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.
Molecular insights into peptide agonist engagement with the PTH1 receptor
Authors: Cary Brian P. , Gerrard Elliot J. , Belousoff Matthew J. , Fletcher Madeleine M. , Jiang Yan , Russell Isabella C. , Piper Sarah J. , Wootten Denise , Sexton Patrick M. 
Published: September 2022

ABSTRACTThe parathyroid hormone (PTH) 1 receptor (PTH1R) is a class B1 G protein-coupled receptor (GPCR) that critically regulates skeletal development and calcium homeostasis. Despite extensive study, the molecular underpinnings of PTH1R stimulation by its cognate hormones, as well as by therapeutic agents, remain unclear. Here, we describe cryo-EM structures of the PTH1R in complex with active fragments of the two hormones, PTH and parathyroid hormone related protein (PTHrP), the peptidic drug abaloparatide, as well as the engineered tool compounds, long-acting PTH (LA-PTH) and the truncated peptide, M-PTH(1-14). We found that the N-terminus of each agonist that is critical for activity, engages the transmembrane bundle in a topologically similar fashion, which reflects similarities in measures of Gαs activation. The full-length peptides bind the extracellular domain (ECD) using a shared interface but induce subtly different ECD orientations relative to the transmembrane domain (TMD). In the structure bound to M-PTH, an agonist which only binds the TMD, the ECD is completely unresolved, demonstrating that the ECD is highly dynamic when unconstrained by a peptide. High resolutions enabled identification of water molecules near the peptide and G protein binding sites, some of which are structurally conserved with other class B1 GPCRs. Our results shed light on the action of orthosteric agonists of the PTH1R and provide a foundation for structure based-drug design.
Advancing single cell technology: iSCseq drives living subcellular transcriptomic profiling in osteoimmune diversity
Authors: Okada Hiroyuki , Terui Yuta , Seki Masahide , Terashima Asuka , Tani Shoichiro , Motooka Daisuke , Kanazawa Sanshiro , Hosonuma Masahiro , Miyahara Junya , Makabe Kenta , Omata Yasunori , Onodera Shoko , Yano Fumiko , Kajiya Hiroshi , Gori Francesca , Saito Taku , Okabe Koji , Suzuki Yutaka , Baron Roland , Chung Ung-il , Tanaka Sakae , Hojo Hironori 
Published: September 2022

SUMMARYSingle-cell RNA-seq (scRNA-seq) has clarified cellular heterogeneity within cell populations. However, scRNA-seq and spatial transcriptomics cannot capture the dynamic transcriptomic changes inside living cells. To decode subcellular gene expression, we developed intra-single cell sequencing (iSCseq), a novel approach that combines confocal imaging, repeatedly picking up cellular components inside living cells, and next-generation sequencing (intra single-cell RNA-seq; iSCseq). iSCseq illustrated the subcellular heterogeneity of gene expression. iSCseq revealed not only multiple differentiation stages embedded in the same cell, but also physical cytoskeletal connections, physiological activity of mitochondria, and intracellular calcium, as confirmed by transcriptomic evidence. Inclusive iSCseq within vivoscRNA-seq datasets identified new osteoclast subsets in physiological and pathological bones. Network analysis with centrality provided insights into the connection between subcellular components, and clearly divided differentiation and fusion processes in multinucleation. The iSCseq approach has the potential to enhance cell biology at subcellular resolution and identify new therapeutic targets.Graphical abstractIn briefintra-single cell sequencing (iSCseq) enhances single-cell technology by combining live cell imaging, subcellular sampling from living cells and sequencing, offering deeper insights into cell functions and pathology at subcellular resolution through inclusive analysis with scRNA-seq and advanced centrality-focused network analysis.Highlightsintra-single cell sequencing (iSCseq) clarifies subcellular heterogeneityiSCseq connects morphological and physiological features with transcriptomeInclusive iSCseq unveils osteoclast subsets in physiological and pathological bonesLinkage at subcellular resolution reveals key players in characteristic fusion
A note on discretising Keyfitz entropy
Authors: de Vries Charlotte , Bernard Connor , Salguero-Gómez Roberto 
Published: September 2022

AbstractKeyfitz’ entropy is a widely used metric to quantify the shape of survivorship of populations, from plants, to animals, and microbes. Keyfitz’ entropy values < 1 correspond to life histories with an increasing mortality rate with age (i.e., actuarial senescence), whereas values > 1 correspond to species with a decreasing mortality rate with age (negative senescence), and a Keyfitz entropy of exactly 1 corresponds to a constant mortality rate with age. Keyfitz’ entropy was originally defined using a continuous-time model, and has since been discretised to facilitate its calculation from discrete-time demographic data. In this short note, we show that the previously used discretisation of the continuous-time metric does not preserve the relationship with increasing, decreasing, or constant mortality rates. To resolve this discrepancy, we propose a new discrete-time formula for Keyfitz’ entropy for age-classified life histories. We show that this new method of discretisation preserves the relationship with increasing, decreasing, or constant mortality rates. We analyse the relationship between the original and the new discretisation, and we find that the existing metric tends to underestimate Keyfitz’ entropy for both short-lived species and long-lived species, thereby introducing a consistent bias. To conclude, to avoid biases when classifying life histories as (non-)senescent, we suggest researchers use either the new metric proposed here, or one of the many previously suggested survivorship shape metrics applicable to discrete-time demographic data such as Gini coefficient or Hayley’s median.
Uptake of aminoglycosides through outer membrane porins in Escherichia coli
Authors: Paul Eshita , Ghai Ishan , Hörömpöli Daniel , Brötz-Oesterhelt Heike , Winterhalter Mathias , Bafna Jayesh A 
Published: September 2022

AbstractAminoglycosides are important clinical antibiotics but their molecular uptake mechanism is still not completely understood. Here we quantify and compare the passive transport of three aminoglycosides (kanamycin, gentamicin, and amikacin) across general or sugar specific porins of Escherichia coli (OmpF, OmpC, LamB and ChiP). Our analysis revealed that permeation of aminoglycosides (Kanamycin/Gentamycin/Amikacin) is about the same through ChiP (≈5/3/2 molecules/s), OmpF (≈10/15/<1 molecules/s) and OmpC (≈11/8/<1 molecules/s). In contrast, LamB of smaller pore diameter has no significant permeation (≤1/1/1 molecules/s, all values recalculated for a gradient of 10 µM). Biological assays confirmed the relevance of these translocations for antibiotic potency.
High-throughput field phenotyping reveals that selection in breeding has affected the phenology and temperature response of wheat in the stem elongation phase
Authors: Roth Lukas , Kronenberg Lukas , Aasen Helge , Walter Achim , Hartung Jens , van Eeuwijk Fred , Piepho Hans-Peter , Hund Andreas 
Published: September 2022

AbstractCrop breeders increasingly need to mitigate the effects of climate change. Ideally, their selection strategies are based on an understanding of crop responses to environmental covariates such as temperature. In this study, the height of 352 varieties (European and Swiss) was repeatedly measured in multiple years. P-splines were used to model plant height as a function of time, from which the phenology parameters jointing (start) and end of stem elongation were derived. An asymptotic model was used to estimate the base-temperature of growth (Tmin), the steepness of the response (lrc), and the growth at optimum temperature (rmax). Parameter rmax had the largest effect on final height, whereas the temperature-response parameters in the narrow sense (Tmin, lrc) were closely connected to phenology. Final height and rmax decreased from the more continental, eastern European countries towards the more maritime, western countries. For genotypes registered in Great Bitain, Tmin was distinctly lower compared to most other regions. Integrating such analysis of in-season responsiveness to fluctuating environmental conditions in breeding will help to improve the genetic gain for climate adaptation. It can only be achieved based on high-throughput assessment of phenotypes in the field throughout the season.HighlightWheat phenology and environmental responses have been affected by breeders’ selections since 1970. High throughput field phenotyping methods reveal these developments, allowing to better adapt future varieties to climate change.
Co-substrate pools can constrain and regulate pathway fluxes in cell metabolism
Authors: West Robert , Delattre Hadrien , Noor Elad , Feliu Elisenda , Soyer Orkun S 
Published: September 2022

ABSTRACTCycling of co-substrates, whereby a metabolite is converted among alternate forms via different reactions, is ubiquitous in metabolism. Several cycled co-substrates are well known as energy and electron carriers (e.g. ATP and NAD(P)H), but there are also other metabolites that act as cycled co-substrates in different parts of central metabolism. Here, we develop a mathematical framework to analyse the effect of co-substrate cycling on metabolic flux. In the cases of a single reaction and linear pathways, we find that co-substrate cycling imposes an additional flux limit on a reaction, distinct to the limit imposed by the kinetics of the primary enzyme catalysing that reaction. Using analytical methods, we show that this additional limit is a function of the total pool size and turnover rate of the cycled co-substrate. Expanding from this insight and using simulations, we show that regulation of co-substrate pool size can allow regulation of flux dynamics in branched and coupled pathways. To support theses theoretical insights, we analysed existing flux measurements and enzyme levels from the central carbon metabolism and identified several reactions that could be limited by co-substrate cycling. We discuss how the limitations imposed by co-substrate cycling provide experimentally testable hypotheses on specific metabolic phenotypes. We conclude that measuring and controlling co-substrate pools is crucial for understanding and engineering the dynamics of metabolism.