bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients
Authors: Liu Fangyan , Duan Mei , Fu Huiqun , Zhao Guoguang , Han Ying , Lan Fei , Ahmed Zara , Cao Guanglei , Li Zheng , Ma Daqing , Wang Tianlong 
Published: June 2022

Objective:
To investigate gut microbiota and intestinal barrier function changes after orthopedic surgery in elderly patients with either normal cognition (NC) or a prodromal Alzheimer disease phenotype (pAD) comprising either subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI).

Background:
Homeostatic disturbances induced by surgical trauma and/or stress can potentially alter the gut microbiota and intestinal barrier function in elderly patients before and after orthopedic surgery.

Methods:
In this prospective cohort study, 135 patients were subject to preoperative neuropsychological assessment and then classified into: NC (n=40), SCD (n=58), or aMCI (n=37). Their gut microbiota, bacterial endotoxin (lipopolysaccharide), tight junction (TJ) protein, and inflammatory cytokines in blood were measured before surgery and on postsurgical day 1, 3, and 7 (or before discharge).

Results:
The short-chain fatty acid (SCFA)-producing bacteria were lower while the gram-negative bacteria, lipopolysaccharide and TJ were higher preoperatively in both the SCD and aMCI (pAD) groups compared with the NC group. After surgery, a decrease in SCFA-producing bacteria, and an increase in both gram-negative bacteria and plasma claudin were significant in the pAD groups relative to the NC group. SCFA-producing bacteria were negatively correlated with TJ and cytokines in pAD patients on postsurgical day 7. Furthermore, surgery-induced perioperative metabolic stress and inflammatory responses were associated with gut microbiota alterations.

Conclusions:
Surgery exacerbates both preexisting microbiota dysbiosis and intestinal barrier dysfunction in pAD patients, all of which may be associated with systemic inflammation and, in turn, may lead to further cognitive deterioration.
Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer
Authors: Wang Lin , Zhang Xiao-Yan , Zhao Yi-Ming , Li Shi-Jie , Li Zhong-Wu , Sun Ying-Shi , Wang Wei-Hu , Wu Ai-Wen ,   on behalf of The Rectal Cancer Cooperative Group of Peking University Cancer Hospital
Published: June 2022

Objective:
To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer.

Background:
Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested.

Methods:
This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate.

Results:
Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%–24.7%] in cCR and 42.9% (95% CI: 6.2%–79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%–78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%–100%), 92.2% (95% CI: 85.5%–98.9%), and 82.7% (95% CI: 73.5%–91.9%), respectively.

Conclusions:
Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.
Evaluation of Fontan-associated Liver Disease and Ethnic Disparities in Long-term Survivors of the Fontan Procedure
Authors: Emamaullee Juliet , Martin Sean , Goldbeck Cameron , Rocque Brittany , Barbetta Arianna , Kohli Rohit , Starnes Vaughn 
Published: June 2022

Objectives:
Fontan-associated liver disease (FALD) has emerged as a nearly universal chronic comorbidity in patients with univentricular congenital heart disease who undergo the Fontan procedure. There is a paucity of data reporting long-term outcomes and the impact of FALD in this population.

Methods:
Patients who underwent the Fontan procedure between 1992 and 2018 were identified using California registry data. Presumed FALD was assessed by a composite of liver disease codes. Primary outcomes were mortality and transplant. Multivariable regression and survival analyses were performed.

Results:
Among 1436 patients post-Fontan, 75.9% studied were adults, with a median follow-up of 12.6 (8.4, 17.3) years. The population was 46.3% Hispanic. Overall survival at 20 years was >80%, but Hispanic patients had higher mortality risk compared with White patients [hazard ratio: 1.49 (1.09–2.03), P=0.012]. Only 225 patients (15.7%) had presumed FALD, although >54% of patients had liver disease by age 25. FALD was associated with later deaths [median: 9.6 (6.4–13.2) years post-Fontan] compared with patients who died without liver disease [4.1 (1.4–10.4) years, P=0.02]. Patients with FALD who underwent combined heart liver transplant had 100% survival at 5 years, compared with only 70.7% of patients who underwent heart transplant alone.

Conclusions:
In this population-based analysis of long-term outcomes post-Fontan, Hispanic ethnicity was associated with increased all-cause mortality. Further, the prevalence of FALD is underrecognized, but our data confirms that its incidence increases with age. FALD is associated with late mortality but excellent posttransplant survival. This emphasizes the need for FALD-specific liver surveillance strategies in patients post-Fontan.
Relatively Poor Long-term Outcomes Following Liver Transplantation for NASH in the United States
Authors: Jamil Omar K. , Sandikçi Burhaneddin , Faust Nolan , Cotter Thomas G. , Paul Sonali , di Sabato Diego , Fung John , Charlton Michael 
Published: June 2022

Background.
Nonalcoholic steatohepatitis (NASH) continues to increase in frequency as an indication for liver transplantation (LT). Data on long-term outcomes for these patients are limited. We aimed to compare long-term patient and graft survival in patients undergoing LT for NASH in the United States to other indications.

Methods.
We analyzed data from the Scientific Registry of Transplant Recipients of adult patients who underwent primary deceased-donor LT from January 1, 2005, to December 31, 2019.

Results.
NASH has increased as an indication for LT by 4.5-fold, from 5.2% in 2005 to 23.4% in 2019. Patient (61.2%) and graft survival (59.2%) at 10 y are significantly poorer for NASH than for all other indications other than alcohol. Patients transplanted for NASH have higher body mass index (32.2 versus 27.6) and greater frequency of diabetes (13% versus 11.6%) than any other indication (P < 0.001). Portal vein thrombosis, location in intensive care unit, dialysis, and pre-LT diabetes (P < 0.001 for all) are independently predictive of patient death and graft loss. Body mass index is not predictive. NASH patients undergoing simultaneous liver kidney have markedly worse 10-y patient and graft survival than liver-only (52.3% versus 62.1%). Graft loss was attributed to recurrence of NASH in <1% of patients.

Conclusions.
LT for NASH is associated with relatively poor long-term patient and graft survival when compared with patients transplanted for other indications, NASH patients undergoing simultaneous liver kidney have the worst long-term outcomes.
Combining Donor-derived Cell-free DNA Fraction and Quantity to Detect Kidney Transplant Rejection Using Molecular Diagnoses and Histology as Confirmation
Authors: Halloran Philip F. , Reeve Jeff , Madill-Thomsen Katelynn S. , Kaur Navchetan , Ahmed Ebad , Cantos Carlos , Al Haj Baddar Nour , Demko Zachary , Liang Nathan , Swenerton Ryan K. , Zimmermann Bernhard G. , Van Hummelen Paul , Prewett Adam , Rabinowitz Matthew , Tabriziani Hossein , Gauthier Phil , Billings Paul ,   the Trifecta Investigators*
Published: June 2022

Background.
Donor-derived cell-free DNA (dd-cfDNA) fraction and quantity have both been shown to be associated with allograft rejection. The present study compared the relative predictive power of each of these variables to the combination of the two, and developed an algorithm incorporating both variables to detect active rejection in renal allograft biopsies.

Methods.
The first 426 sequential indication biopsy samples collected from the Trifecta study (ClinicalTrials.gov # NCT04239703) with microarray-derived gene expression and dd-cfDNA results were included. After exclusions to simulate intended clinical use, 367 samples were analyzed. Biopsies were assessed using the molecular microscope diagnostic system and histology (Banff 2019). Logistic regression analysis examined whether combining dd-cfDNA fraction and quantity adds predictive value to either alone. The first 149 sequential samples were used to develop a two-threshold algorithm and the next 218 to validate the algorithm.

Results.
In regression, the combination of dd-cfDNA fraction and quantity was found to be significantly more predictive than either variable alone (P = 0.009 and P < 0.0001). In the test set, the area under the receiver operating characteristic curve of the two-variable system was 0.88, and performance of the two-threshold algorithm showed a sensitivity of 83.1% and specificity of 81.0% for molecular diagnoses and a sensitivity of 73.5% and specificity of 80.8% for histology diagnoses.

Conclusions.
This prospective, biopsy-matched, multisite dd-cfDNA study in kidney transplant patients found that the combination of dd-cfDNA fraction and quantity was more powerful than either dd-cfDNA fraction or quantity alone and validated a novel two-threshold algorithm incorporating both variables.
Preclinical efficacy of bacosides-lauric acid nano-herbal formulation in comparison to rivastigmine for treatment of Alzheimer’s disease
Authors: Kumar Ashish , Goyal Kritika , Pal Muneesh , Upadhyay Prabhat , Gupta Sarika , Koul Veena , Konar Arpita 
Published: June 2022

AbstractDespite decades of rigorous scientific endeavors for Alzheimer’s disease (AD) drug development, massive failures in clinical trials is continuously posing healthcare and societal burden. Currently recommended single targeted drugs including rivastigmine with limited bioavailability can alleviate AD symptoms only for a limited period of time but unable to reverse the disease progression. Recent evidences consider poly-pharmacological and multi-targeted agents aiming at amyloid and tau burden, neuroinflammation, neuroprotection and cognitive enhancement as potential treatment options. In this regard, bioactive herbal compounds with holistic action and minimal adversities have gained prominence, though lacunae in their scientific validation and limited bio-permeability to cross BBB represent major hurdles. Previously, we showed that lactoferrin conjugated PEG-S-S-PLA-PCL-OH efficaciously delivered herbal compounds to brain and such nano-herbal formulation of bacosides-lauric acid (BAN-LAN) attenuated neuronal damages induced by scopolamine in vitro. Here, we tested the preclinical potential of BAN-LAN in reversal of AD pathologies in 5XFAD transgenic mice. Our nano-herbal formulation substantially reduced amyloid burden by clearing Aβ plaques in the hippocampus of 5XFAD mice and also attenuated aβ42 induced alterations in AD associated gene expression in hippocampal neurons in vitro. It showed neuroprotection by rescuing neuronal damage and promoting neurogenesis in the hippocampus of AD transgenic mice. Anti-neuroinflammatory properties were also exhibited by the formulation as evident from inhibition of hippocampal astrocytic and microglial activation in 5XFAD mice. BAN-LAN showed cognitive efficacy by restoring memory impairment in AD transgenic mice and effects were more pronounced than unconjugated natural form and rivastigmine. These findings suggest that BAN-LAN may serve as a promising therapeutic agent for AD with better brain penetration and targeting multiple AD pathways.
Spontaneous electroretinogram signals to screen people with early risk factors for diabetic retinopathy
Authors: Noguez Imm Ramsés , Muñoz-Benitez Julio , Medina Diego , Barcenas Everardo , Molero-Castillo Guillermo , Reyes-Ortega Pamela , Hughes-Cano Jorge Armando , Medrano-Gracia Leticia , Miranda-Anaya Manuel , Rojas-Piloni Gerardo , Quiroz-Mercado Hugo , Hernández-Zimbrón Luis Fernando , Fajardo-Cruz Elisa Denisse , Ferreyra-Severo Ezequiel , García-Franco Renata , López-Star Ellery , García-Roa Marlon , Lansingh Van Charles , Thébault Stéphanie C. 
Published: June 2022

AbstractGiven the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, but existing methods are insufficient to screen early risk factors of diabetic retinopathy (DR). Here, we introduce non-evoked ERG as a simple, fast modality to record spontaneous activity, from which we developed a single random forest-based model that predicts disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome. Classification performance was validated using a dataset from an independent eye center. Our algorithm can be coupled with different ERG sensors, including ones working with portative, non-mydriatic devices. Principal component and discriminant analysis suggest slow spontaneous ERG frequencies as main discriminators for our predictive model. Our study will facilitate the implementation of interventions for the prevention of overweight and obesity by providing a robust, quantitative, and non-invasive identification and follow-up approach, which should ultimately reduce DR incidence.
IMMUNE GENE REGULATION IN THE GUT DURING METAMORPHOSIS IN TWO HOLO- VERSUS A HEMIMETABOLOUS INSECT
Authors: Manthey Christin , Johnston Paul R. , Rolff Jens 
Published: June 2022

AbstractDuring complete metamorphosis, holometabolous insects remodel their entire anatomy, including the gut and must control their microbiota to avoid infectious disease. High activity of antimicrobial peptides and proteins in the gut during metamorphosis has been best described in several Lepidoptera. The immune system of the dipteran Drosophila melanogaster also controls the number of bacteria during metamorphosis. However, little is known about the regulation of immune genes during the larval–adult moult in Hemimetabola which undergo less drastic metamorphic changes. Different patterns of immune effector expression during metamorphosis were shown in a study comparing the lepidopteran Galleria mellonela and the orthopteran Gryllus bimaculatus, where G. mellonella showed a strong up-regulation of antimicrobial peptides in the gut at the larval-pupal moult but not G. bimaculatus. Whether these findings reflect general patterns within holometabolous versus hemimetabolous insects remains unclear. Using RNAseq, we compare the expression of immune effector genes in the gut during metamorphosis in two holometabolous (Calliphora vicina and Tenebrio molitor) and a hemimetabolous insect (Pyrrhocoris apterus). We found high read count abundances of differentially expressed immune effectors in the gut at the larval-pupal moult in C. vicina and T. molitor; no such high abundances were observed at the larval-adult moult in P. apterus. Our findings confirm that only complete metamorphosis elicits a prophylactic immune response as an adaptive response in holometabolous insects, which controls the microbiota during gut replacement.
A study of hyperelastic continuum models for isotropic athermal fibrous networks
Authors: Song Dawei , Oberai Assad A , Janmey Paul A 
Published: June 2022

AbstractMany biological materials contain fibrous protein networks as their main structural components. Understanding the mechanical properties of such networks is important for creating biomimicking materials for cell and tissue engineering, and for developing novel tools for detecting and diagnosing disease. In this work, we develop continuum models for isotropic, athermal fibrous networks by combining a single-fiber model that describes the axial response of individual fibers, with network models that assemble individual fiber properties into overall network behavior. In particular, we consider four different network models, including the affine, three-chain, eight-chain, and micro-sphere models, which employ different assumptions about network structure and kinematics. We systematically investigate the ability of these models to describe the mechanical response of athermal collagen and fibrin networks by comparing model predictions with experimental data. We test how each model captures network behavior under three different loading conditions: uniaxial tension, simple shear, and combined tension and shear. We find that the affine and three-chain models can accurately describe both the axial and shear behavior, whereas the eight-chain and micro-sphere models fail to capture the shear response, leading to an unphysical zero shear moduli at infinitesimal strains. Our study is the first to systematically investigate the applicability of popular network models for describing the macroscopic behavior of athermal fibrous networks, offering insights for selecting efficient models that can be used for large-scale, finite-element simulations of athermal networks.
A knowledge-based view of emerging market firm internationalization: the case of the Indian IT industry
Authors: Ray Pradeep , Ray Sangeeta , Kumar Vikas 
Published: June 2022

PurposeContemporary frameworks in the resource-based view (RBV) of the firm observe that the proprietary firm-specific assets of multinational companies (MNCs) from developed economies give them competitive advantage in international markets. However, the question “how do emerging market firms (EMFs) achieve accelerated internationalisation in knowledge based industries – despite not possessing proprietary assets and lacking critical elements of innovation eco-systems, institutions and infrastructure” has yet to be addressed. This paper aims to adopt a knowledge-based view (KBV) of the firm, identifying knowledge, both inside and outside of the firm, as a critical element for the internationalization of EMFs.Design/methodology/approachThis research entailed deductive econometric analyses using panel data analysis from 925 firm-year observations, which tested our predictions on capabilities that contribute to the internationalization of EMFs from the IT industry in India.FindingsThe findings of the authors’ panel data analysis reveal that the capacity to internationalize is predicated by knowledge leverage in three principal domains: absorptive capacity, tacit knowledge and knowledge-codification. This study shows internationalization is driven by higher-order capabilities of EMFs that draw on the absorptive capacity of individuals and collectives as a dynamic capability to serve international clients worldwide.Research limitations/implicationsThis study highlights that the process by which EMFs gain competence is different to the Western MNCs insofar as the extent to which EMFs have to stretch their efforts of learning from clients.Practical implicationsFor practitioners, the findings of this research are a useful guide to understand that EMFs need to make strategic investments to understand the idiosyncrasies of a variety of clients’ needs and operating environments to dynamically adapt, document the learning and leverage the tacit knowledge.Social implicationsThis study captures the innate ability of entrepreneurs in emerging economies to unlock their potential in human capital for globalizing operations and targeting new market segments in the industry. This can directly benefit in uplifting the income level of millions in relatively underdeveloped countries and bringing about much-needed equity in the level of income in the society.Originality/valueThe value of this study lies in its novel and contemporary insight on how EMFs leapfrog in a fast-changing technology space. What distinguishes the work from the static framework in literature is that EMFs learning is dynamic, and happens in an interactive mode, alongside clients in close proximity. This study captures the innate ability of entrepreneurs to unlock the potential of human capital in emerging economies for globalizing operations.
Interagency and global coalitions in combating illicit financial flows: the case of Nigeria
Authors: Ebire Kolawole , Daniels Patrick Olasehinde 
Published: June 2022

Purpose
This paper aims to assess the roles of agencies in combating illicit financial flows (IFFs) in Nigeria. Specifically, this paper explores the roles of the major anti-corruption agencies – the Economic and Financial Crimes Commission (EFCC) and Independent Corrupt Practices and other Related Offences Commission (ICPC) – in curbing IFFs in Nigeria. This paper reviews the various activities and achievements of these agencies in combating IFFs and concludes that in spite of the effort made by these anti-graft agencies, Nigeria still ranks top among African countries suffering from IFFs. Therefore, this study recommends a need for a collective and coordinated strategy by authorities worldwide to address the difficulties posed by financial crimes.

Design/methodology/approach
This study reviews the roles of anti-graft agencies in combating IFFs in Nigeria. Specifically, this study explores the roles of EFCC and ICPC in combating IFFs.

Findings
This study concludes that in spite of the effort made by Nigeria’s anti-graft agencies, IFFs have continued to increase thereby impeding the effort to achieve Sustainable Development Goal 16.4 – reduce IFFs.

Originality/value
This study contributes to the existing body of knowledge by exploring Nigeria's major anti-graft agencies and their effort in curbing IFFs in Nigeria.