bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Environmental Targeting in the Amazon Rainforest
Authors: Assunção Juliano , McMillan Robert , Murphy Joshua , Souza-Rodrigues Eduardo 
Published: October 2022

Abstract
This article sets out a data-driven approach for targeting environmental policies optimally in order to combat deforestation. We focus on the Amazon, the world’s most extensive rainforest, where Brazil’s federal government issued a “Priority List” of municipalities in 2008—a blacklist to be targeted with more intense environmental monitoring and enforcement. First, we estimate the causal impact of the Priority List on deforestation (along with other relevant treatment effects) using “changes-in-changes” due to Athey and Imbens (2006), finding that it reduced deforestation by 43$\%$ and cut emissions by almost 50 million tons of carbon. Second, we develop a novel framework for computing targeted optimal blacklists that draws on our treatment effect estimates, assigning municipalities to a counterfactual list that minimizes total deforestation subject to realistic resource constraints. We show that the ex post optimal list would result in carbon emissions over 10$\%$ lower than the actual list, amounting to savings of more than $ \$ $1.2 billion (34$\%$ of the total value of the Priority List), with emissions over 23$\%$ lower on average than a randomly selected list. The approach we propose is relevant both for assessing targeted counterfactual policies to reduce deforestation and for quantifying the impacts of policy targeting more generally.
iPSC-Derived Airway Epithelial Cells: Progress, Promise, and Challenges
Authors: Yu Fenggang , Liu Fei , Liang Xiaohua , Duan Linwei , Li Qiongqiong , Pan Ge , Ma Chengyao , Liu Minmin , Li Mingyue , Wang Peng , Zhao Xuening 
Published: October 2022

Abstract
Induced pluripotent stem cells (iPSCs) generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide an unlimited source of cells that can be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. This review gives a comprehensive overview of recent progress toward the use of iPSCs to generate proximal and distal airway epithelial cells and mix lung organoids. Furthermore, their potential applications and future challenges for the field are discussed, with a focus on the technological hurdles that must be cleared before stem cell therapeutics can be used for clinical treatment.
Molecular Characterization of Peronospora variabilis Isolates Infecting Chenopodium quinoa and Chenopodium album in Spain
Authors: Fondevilla Sara , Arias-Giraldo Luis F. , García-León Francisco Javier , Landa Blanca B. 
Published: October 2022

Quinoa is an expanding crop in southern Spain. Downy mildew, caused by Peronospora variabilis, is the most important quinoa disease in Spain and worldwide. In Spain, this disease has also been observed on the weed Chenopodium album. The objectives of this study were to unravel the origin of the P. variabilis isolates currently infecting quinoa in southern Spain and to study their genetic diversity. We hypothesized that P. variabilis isolates infecting quinoa in Spain could have been introduced through the seeds of the quinoa varieties currently grown in the country or, alternatively, that these isolates are endemic isolates, originally infecting C. album, that jumped to quinoa. In order to test these hypotheses, we sequenced the internal transcribed spacer (ITS), cytochrome c oxidase subunit 1 (cox1), and cox2 regions of 33 P. variabilis isolates infecting C. quinoa and C. album in southern Spain and analyzed their phylogenetic relationship with isolates present in other countries infecting Chenopodium spp. cox1 gene sequences from all of the Spanish P. variabilis isolates were identical and exhibited nine single-nucleotide polymorphisms (SNPs) compared with a single P. variabilis cox1 sequence found at GenBank. Phylogenetic analyses based on the ITS ribosomal DNA region were not suitable to differentiate isolates according to their geographical origin or host. The cox2 sequences from P. variabilis Spanish isolates collected from C. quinoa and C. album were all identical and had a distinctive SNP in the last of four polymorphic sites that distinguished Spanish isolates from isolates from other countries. These results suggest that P. variabilis infecting quinoa in southern Spain could be native isolates that originally infected C. album. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Disentangling the signaling complexity of nerve growth factor receptors byCRISPR/Cas9
Authors: Testa Giovanna , Mainardi Marco , Vannini Eleonora , Pancrazi Laura , Cattaneo Antonino , Costa Mario 
Published: October 2022

AbstractThe binding of nerve growth factor (NGF) to the tropomyosin–related kinase A (TrkA) and p75NTRreceptors activates a large variety of pathways regulating critical processes as diverse as proliferation, differentiation, membrane potential, synaptic plasticity, and pain. To ascertain the details of TrkA‐p75NTRinteraction and cooperation, a plethora of experiments, mostly based on receptor overexpression or downregulation, have been performed. Among the heterogeneous cellular systems used for studying NGF signaling, the PC12 pheochromocytoma‐derived cell line is a widely used model. By means of CRISPR/Cas9 genome editing, we created PC12 cells lackingTrkA,p75NTR, or both. We found that TrkA‐null cells become unresponsive to NGF. Conversely, the absence of p75NTRenhances the phosphorylation of TrkA and its effectors. Using a patch‐clamp, we demonstrated that the individual activation of TrkA and p75NTRby NGF results in antagonizing effects on the membrane potential. These newly developed PC12 cell lines can be used to investigate the specific roles of TrkA and p75NTRin a genetically defined cellular model, thus providing a useful platform for future studies and further gene editing.
Chemoprophylactic Anticoagulation Following Lumbar Surgery Significantly Reduces Thromboembolic Events After Instrumented Fusions, Not Decompressions
Authors: Cloney Michael , Hopkins Benjamin , Dhillon Ekamjeet , El Tecle Najib , Koski Tyler R. , Dahdaleh Nader S. 
Published: October 2022

Study Design:
Retrospective cohort

Objective.
To quantify any reduction in venous thromboembolic events (VTE) caused by chemoprophylaxis among lumbar surgery patients.

Summary of Background Data.
Chemoprophylactic anticoagulation (chemoprophylaxis) is used to prevent VTE after lumbar surgery. However, the treatment effect of chemoprophylaxis has not been reported among spine surgery patients, as conventional statistical methods preclude such inferences.

Methods.
1243 consecutive lumbar fusions and 1433 non-instrumented lumbar decompressions performed at our institution over a six-year period were identified, and clinical and demographic data were collected, including on VTE events within 30 days postoperatively. Instrumented lumbar fusions and non-instrumented lumbar surgeries were analyzed separately. Patients who were given chemoprophylaxis (treatment) and controls were matched according to known VTE risk factors, including age, body mass index, sex, diabetes, chronic kidney disease, history of VTE, estimated blood loss, length of surgery, transfusion, whether surgery was staged, and whether surgery used an anterior approach. K-nearest neighbor propensity score matching was performed, and the treatment effect of chemoprophylaxis was calculated.

Results.
Unadjusted, there was no difference in the rate of VTE between treatment and controls in either population. Baseline clinical and demographic characteristics differed significantly between treatment and control groups. 575 lumbar fusion patients and 435 non-instrumented lumbar decompression patients were successfully propensity score matched, yielding balanced models (Rubin’s B<25, 0.5<Rubin’s R<2.0) and >60% reduction in known bias for both populations. The treatment effect of chemoprophylaxis after lumbar fusion in our patient population was a reduction in VTE incidence from 9.4% to 4.2% (P<0.05), and propensity score adjusted regression confirmed a reduced odds of VTE with chemoprophylaxis (OR=0.37, P=0.035). The treatment effect was not significant for non-instrumented lumbar decompression patients.

Conclusion.
Among patients undergoing instrumented lumbar fusions, chemoprophylactic anticoagulation causes a significant reduction in VTE, but causes no significant reduction among patients undergoing non-instrumented lumbar decompression.
Impact of Health Literacy on Self-Reported Health Outcomes in Spine Patients
Authors: Lans Amanda , Bales John R. , Borkhetaria Pranati , Schwab Joseph H. , Verlaan Jorrit-Jan , Rossi Laura P. , Tobert Daniel G. 
Published: October 2022

Study Design.
Cross-sectional survey study.

Objective.
The aim was to determine if health literacy level is associated with patient-reported outcomes and self-reported health status among patients presenting to an academic outpatient spine center.

Summary of Background Data.
Patient reports are critical to assessing symptom severity and treatment success in orthopedic spine patients. Patient-reported outcome measures (PROMs) are important instruments commonly used for this purpose. However, the influence of patient health literacy on PROMs has not yet been given much consideration in spine literature.

Materials and Methods.
Consecutive English-speaking patients over the age of 18 years and new to our clinic verbally completed the Newest Vital Sign health literacy assessment tool and a sociodemographic survey, including self-reported health status. In addition, seven Patient-Reported Outcomes Measurement Information System scores were extracted from patient records. Regression modeling was performed with PROMs considered as dependent variables, health literacy level as the primary predictor, and all other factors (age, sex, race, ethnicity, native English speaker, highest educational degree, grade-level reading, marital status, employment status, annual household income, and type of insurance) as covariates.

Results.
Among the 318 included patients, 33% had limited health literacy. Adjusted regression analysis demonstrated that patients with limited health literacy had worse PROM scores across all seven domains (Physical Function: P=0.028; Depression: P=0.035; Global Health—Physical: P=0.001; Global Health—Mental: P=0.007; Pain Interference: P=0.036; Pain Intensity: P=0.002; Anxiety: P=0.047). In addition, patients with limited health literacy reported worse self-reported health status (P<0.001).

Conclusions.
Spine patients with limited health literacy have worse baseline PROM scores confounders and report worse general health. Further investigations are necessary to elucidate if limited health literacy is a marker or the root cause of these disparities. Findings from this study urge the consideration of patient health literacy when interpreting PROMs as well as the implications for patient assessment and discussion of treatment options.
Neurological Safety of Endoscopic Transforaminal Lumbar Interbody Fusion: A Magnetic Resonance Neurography Study
Authors: Yang Xinyu , Wang Lianlei , Yang Qing , Su Junxiao , Qiu Cheng , Ibrahim Yakubu , Yuan Suomao , Tian Yonghao , Liu Xinyu 
Published: October 2022

Objective.
A magnetic resonance neurography (MRN) study was conducted to assess the neurological safety of endoscopic transforaminal lumbar intervertebral fusion (endo-TLIF).

Materials and Methods.
A total of 56 healthy volunteers (29 men, 27 women; average age, 44 yr; age range, 21–60 yr) were included in the study. Coronal MRN images were collected from L2/L3 to L5/S1. The working triangle, modified working zone, and safest working zone areas, as well as the vertical and horizontal safe operation diameters, were measured. Linear regression analyses were conducted to explore the correlations between general characteristics (sex, age, height, body mass index) and the measured radiographic indicators.

Results.
MRN can effectively evaluate the operation zone of endo-TLIF. The safest working zone, modified working zone, and working triangle areas were largest at L4/L5 (92.4±23.4, 136±35.6, and 197±41.7 mm2, respectively) and smallest at L2/L3 (45.5±12.9, 68.1±19.5, and 92.6±24.4 mm2, respectively). The vertical safe operation diameter was large at L4/L5 and L2/L3 (5.34±0.8 and 5.42±0.9 mm, respectively) and smallest at L5/S1 (2.94±0.9 mm). The horizontal safe operation diameter was large at L4/L5 (7.28±1.2 mm) and smaller at L5/S1 and L2/L3 (4.28±1.0 and 4.77±0.8 mm, respectively).

Conclusions.
L4/L5 has the lowest risk of nerve injury, and may be the safest level for beginners initiating endo-TLIF in their practice. We recommend that coronal MRN is routinely performed before endo-TLIF to minimize the risk of neurological injury.
Safety and Accuracy of Freehand Pedicle Screw Placement and the Role of Intraoperative O-arm: A Single Institution Experience
Authors: Alomari Safwan , Lubelski Daniel , Lehner Kurt , Tang Anthony , Wolinsky Jean-Paul , Theodore Nicholas , Sciubba Daniel M. , Larry Lo Sheng-fu , Belzberg Allan , Weingart Jon , Witham Timothy , Gokaslan Ziya L. , Bydon Ali 
Published: October 2022

Study Design:
Retrospective cohort study.

Objective:
To investigate the accuracy of pedicle screw placement by freehand technique and to compare revision surgery rates among three different imaging verification pathways.

Summary of Background Data:
Studies comparing different imaging modalities in freehand screw placement surgery are limited.

Methods:
A single-institution retrospective chart review identified adult patients who underwent freehand pedicle screw placement in the thoracic, lumbar or sacral levels. Patients were stratified into three cohorts based on the intraoperative imaging modality used to assess the accuracy of screw position: intraoperative X-Rays (cohort 1); intraoperative O-arm (cohort 2); or intraoperative CT-scan (cohort 3). Postoperative CT-scans were performed on all patients in cohorts 1 and 2. Postoperative CT-scan was not required in cohort 3. Screw accuracy was assessed using the Gertzbein-Robbins grading system.

Results:
9,179 pedicle screws were placed in the thoracic or lumbosacral spine in 1311 patients. 210 (2.3%) screws were identified as Gertzbein-Robbins grades C-E on intra/post-operative CT-scan, 137 thoracic screws , and 73 lumbar screws (P<0.001). 409 patients underwent placement of 2,754 screws followed by intraoperative X-Ray (cohort 1); 793 patients underwent placement of 5,587 screws followed by intraoperative O-arm (cohort 2); and 109 patients underwent placement of 838 screws followed by intraoperative CT-scan (cohort 3). Postoperative CT-scans identified 65 (2.4%) and 127 (2.3%) malpositioned screws in cohorts 1 and 2, respectively. 11 screws (0.12%) were significantly malpositioned and required a second operation for screw revision. 9 patients (0.69%) required revision operations: 8 of these patients were from cohort 1 and 1 patient was from cohort 2.

Conclusion:
When compared to intraoperative X-Ray, intraoperative O-arm verification decreased the revision surgery rate for malpositioned screws from 0.37% to 0.02%. In addition, our analysis suggests that the use of intraoperative O-arm can obviate the need for postoperative CT scans.
Disability-adjusted life years and the trends of the burden of colorectal cancer: a population-based study in Shanghai, China during 2002 to 2016
Authors: Zhong Wei , Chen Liping , Li Xiaopan , Chen Yichen , Zhang Yao , Guo Canjie , Shen Yufeng , Chen Huimin 
Published: October 2022

Abstract

Backgrounds:
Colorectal cancer (CRC) still ranks the top in morbidity and mortality of cancers worldwide, posing a huge threat and burden to the society. We aimed to determine the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) of CRC and explore potential changes in the temporal trends of the CRC burden in Shanghai during 2002 to 2016.

Methods:
The cancer statistics and demographics were obtained from the Cancer Registry and the Statistics Bureau of Pudong New Area, respectively. Data from 2002 to 2016 were included and analyzed retrospectively. DALYs were calculated using DisMod and the age-standardized rates (ASRs) were obtained according to Segi world standard population. Joinpoint regression was used to measure the trends in CRC incidence and to estimate the annual percent change.

Results:
The increasing trend of CRC ASR incidence halted after 2014, coinciding with the introduction of the Shanghai CRC screening program. The ASRs of mortality and DALYs increased, at 0.42% (P < 0.05) and 4.07% (P < 0.001) per year, respectively, which were mainly driven by men and individuals aged above the CRC screening program target.

Conclusions:
The disease burden of CRC in Shanghai remains serious, especially among men, and individuals aged >74 years. The benefits of the screening program have been partially proven by the ASRs of CRC incidence, providing important insights into better and wider application of screening programs.
Pharmacodynamic Monitoring of Ciclosporin and Tacrolimus: Insights From Nuclear Factor of Activated T-Cell–Regulated Gene Expression in Healthy Volunteers
Authors: Djaelani Yoana Aurelia , Giese Thomas , Sommerer Claudia , Czock David 
Published: October 2022

Background:
Although therapeutic drug monitoring of calcineurin inhibitor (CNI) concentrations is performed routinely in clinical practice, an identical concentration may lead to different effects in different patients. Although the quantification of nuclear factor of activated T-cell–regulated gene expression (NFAT-RGE) is a promising method for measuring individual CNI effects, CNI pharmacodynamics are as of yet incompletely understood.

Methods:
CNI concentrations and NFAT-RGEs were quantified in 24 healthy volunteers receiving either ciclosporin or tacrolimus in 2 clinical trials. NFAT-RGE was measured using quantitative reverse transcription polymerase chain reaction tests of whole-blood samples. Pharmacokinetics and pharmacodynamics were analyzed using compartmental modeling and simulation. In addition, NFAT-RGE data from renal transplant patients were analyzed.

Results:
The average NFAT-RGE during a dose interval was reduced to approximately 50% with ciclosporin, considering circadian changes. The different effect–time course with ciclosporin and tacrolimus could be explained by differences in potency (IC50 204 ± 41 versus 15.1 ± 3.2 mcg/L, P < 0.001) and pharmacokinetics. Residual NFAT-RGE at the time of maximum concentration (RGEtmax) of 15% when using ciclosporin and of 30% when using tacrolimus was associated with similar average NFAT-RGEs during a dose interval. Renal transplant patients had similar but slightly stronger effects compared with healthy volunteers.

Conclusions:
Ciclosporin and tacrolimus led to similar average suppression of NFAT-RGE in a dose interval, despite considerably different RGEtmax. Pharmacodynamic monitoring of average NFAT-RGE should be considered. When using NFAT-RGE at specific time points, the different effect–time courses and circadian changes of NFAT-RGEs should be considered.
Influence of Genetic Polymorphisms on the Pharmacokinetics of Trazodone Hydrochloride: A Scoping Review and Future Perspective
Authors: Meulman Jessica , Visacri Marília Berlofa , Moriel Patricia , Pincinato Eder de Carvalho 
Published: October 2022

Background:
Trazodone hydrochloride is an antidepressant used in clinical practice. As a substrate of cytochrome P450 enzymes that is vulnerable to P-glycoprotein transport, several factors can alter its plasma concentration, and hence, dose adjustment may be required. The aim of this scoping review was to identify genetic polymorphisms that influence the pharmacokinetics of trazodone hydrochloride.

Methods:
A literature search was performed using PubMed, PubMed Central, BVS/BIREME, EBSCOhost, Web of Science, Embase, Cochrane Library, and Medline databases for studies published until August 2021. The search strategy was based on the following keywords: Trazodone OR “m-chlorophenyl piperazine” AND “Pharmacogenetics” OR “Genetics” OR “Cytochrome P-450 Enzyme System” OR “Polymorphism, Single Nucleotide” OR “Polymorphism, Genetic.”

Results:
The search retrieved 684 candidate articles; 307 duplicates were eliminated. In total, 377 articles were eligible for the first screen. However, only 4 met the eligibility criteria, and 12 polymorphisms in 5 different genes (CYP2D6, CYP1A2, CYP3A4, CYP3A5, and ABCB1). Notably, only C3435T ABCB1 influenced the pharmacokinetics of trazodone hydrochloride. Individuals with the T/T genotype had lower area under the curve, half-life, and maximum concentration values with a higher clearance rate.

Conclusions:
Polymorphisms in CYP450 do not seem to directly influence the pharmacokinetics of trazodone hydrochloride or its metabolites. By contrast, genetic polymorphisms in ABCB1 seem to have an important effect on the pharmacokinetics of trazodone hydrochloride by enhancing drug metabolism and elimination.
Microsurgical Complications after Finger Reimplantation Treated with Negative Pressure Wound Therapy: A Case Report
Authors: Quintero Jorge I. , Moreno-Serrano Constanza , Bermúdez Julio C. ,   Hand and Microsurgery Research Group
Published: October 2022

Summary:
Venous congestion is the most critical complication following microsurgical finger replantation and can present within the first postoperative days or even in the immediate postoperative period. This is a case series of three patients who underwent digit replantation. The postoperative complication was venous congestion, and immediately, negative pressure wound therapy (NPWT) was applied to reduce the risk of failure. Three patients with a range of 35 years of age were included. One index finger, one thumb, and one ring finger were the fingers amputated; the surgical technique was described; our anticoagulant protocol was demonstrated; and finally, standardization of the NPWT was established. At the end of the therapy, all fingers survived. We concluded that NPWT is an excellent treatment option following the identification of venous congestion in digit replantation.
A Technical Guide for Sciatic Nerve Targeted Muscle Reinnervation in a Transfemoral Amputee
Authors: Lister Rachel C. , Tsui Jane M. , Naram Aparajit 
Published: October 2022

Background:
There are approximately 2 million people living with the loss of a major limb in America. It is estimated that 95% of these will have some form of pain associated with their amputation. Phantom limb pain, related to symptomatic neuromas, contributes to amputation morbidity and can be difficult to treat. Studies have shown that targeted muscle reinnervation (TMR), by giving symptomatic neuromas “somewhere to go and something to do,” can be an effective therapy. However, a large proportion of surgeons still treat symptomatic neuromas by burying them in nearby tissue.

Methods:
We treated a patient with previous above-the-knee amputation, complicated by a symptomatic neuroma, with TMR. We identified and described nine steps to the procedure. Our description is accompanied by illustrative, intraoperative photographs and technical pearls.

Results:
This article provides a description of TMR technique involving a neuroma of the sciatic nerve and its branches, to treat an above-the-knee amputation, with the aim of making this approach more accessible. At 9-month follow-up, the patient had active firing of the recipient muscles with donor nerve stimulation indicating successful reinnervation. The patient continued to report stump pain, but with intermittent pain-free days.

Conclusions:
TMR has proven potential as a therapy for amputation-related, neuropathic pain. With this technical guide to TMR, surgeons should feel more comfortable adding this technique to their armamentarium, to be utilized either at the time of amputation or as a secondary measure.