bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residential proximity to hydraulically fractured oil and gas wells and adverse birth outcomes in urban and rural communities in California (2006–2015)
Authors: Tran Kathy V. , Casey Joan A. , Cushing Lara J. , Morello-Frosch Rachel 
Published: October 2021

Background:
Prenatal exposure to hydraulic fracturing (HF), a chemically intensive oil and gas extraction method, may be associated with adverse birth outcomes, but no health studies have been conducted in California.

Methods:
We conducted a retrospective cohort study of 979,961 births to mothers in eight California counties with HF between 2006 and 2015. Exposed individuals had at least 1 well hydraulically fractured within 1 km of their residence during pregnancy; the reference population had no wells within 1 km, but at least one oil/gas well within 10 km. We examined associations between HF and low birth weight (LBW), preterm birth (PTB), small for gestational age birth (SGA), and term birth weight (tBW) using generalized estimating equations and assessing urban-rural effect modification in stratified models.

Results:
Fewer than 1% of mothers (N = 1,192) were exposed to HF during pregnancy. Among rural mothers, HF exposure was associated with increased odds of LBW (odds ratio [OR] = 1.74; 95% confidence interval [CI] = 1.10, 2.75), SGA (OR = 1.68; 95% CI = 1.42, 2.27) and PTB (OR = 1.17; 95% CI = 0.64, 2.12), and lower tBW (mean difference: –73 g; 95% CI = –131, –15). Among urban mothers, HF exposure was positively associated with SGA (OR = 1.23; 95% CI = 0.98, 1.55), inversely associated with LBW (OR = 0.83; 95% CI = 0.63, 1.07) and PTB (OR = 0.65; 95% CI = 0.48, 0.87), and not associated with tBW (mean difference: –2 g; 95% CI = –35, 31).

Conclusion:
HF proximity was associated with adverse birth outcomes, particularly among rural Californians.
Pancreatic Pain—Knowledge Gaps and Research Opportunities in Children and Adults
Authors: Uc Aliye , Andersen Dana K. , Apkarian A. Vania , Bellin Melena D. , Colloca Luana , Drewes Asbjørn M. , Dunbar Ellyn K. , Forsmark Christopher E. , Goodman Marc T. , Kapural Leonardo , Koob George F. , Palermo Tonya M. , Pandol Stephen J. , Pasricha Pankaj , Phillips Anna E. , Piomelli Daniele , Saloman Jami L. , Schwarzenberg Sarah Jane , Singh Vikesh K. , Sowa Gwendolyn , Strouse Thomas , Treisman Glenn J. , Windsor John A. , Yadav Dhiraj 
Published: October 2021

Abstract
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.
Modified Lengthening Temporalis Myoplasty Using an Intraoral Approach
Authors: Hayashi Ayato , Natori Yuhei , Suda Shunichi , Kamimori Tomoki , Nojiri Gaku , Uchiyama Mizuki , Labbé Daniel 
Published: October 2021

Background:
Lengthening temporalis myoplasty (LTM) is a unique and definite facial reanimation procedure that involves inserting the whole temporal tendon directly into the nasolabial fold. However, the nasolabial fold incision remains one of the difficulties of this procedure, particularly in young or female patient. To avoid the need for this incision, the authors developed an intraoral approach to manipulate the temporal muscle tendon toward the nasolabial fold. in this study, we describe the details of this procedure.

Method:
The authors performed their intraoral approach procedure in 5 patients with established complete facial paralysis. instead of making an incision at the nasolabial fold to approach the coronoid process, the authors made the incision at the buccal mucosa. The results were evaluated both subjectively and objectively.

Results:
The authors achieved facial reanimation without leaving any obvious scar on the face or neck and the effect of static reconstruction is obvious, even immediately after the surgery. All the patients obtained good facial movement within 4 months (2.5 months in average), and improved all evaluated parameters postoperatively. No infections or other major complications were reported following surgery; however, 1 patient developed a slight dimple that required revision.

Discussion:
The authors could advance temporal tendon toward nasolabial fold firmly obtaining sufficient surgical field similar to that of nasolabial fold incision, and achieved fairly good results without an obvious scar on the face.
Establishing LTM without nasolabial fold incision, we could expand the indication of LTM more widely, and it could be more familiar procedure for smile reanimation in all generation.
Correction of a Secondary Bilateral Cleft Lip Nasal Deformity in Adults Using Repositioning of Both Lower Lateral Cartilages and Nasal Tip Plasty Through an Open Bilateral Reverse-U Incision
Authors: Ryu Jeong Yeop , Lee Jung Ho , Lee Joon Seok , Lee Jeong Woo , Choi Kang Young , Cho Byung Chae 
Published: October 2021

Background:
Correcting a secondary bilateral cleft lip nasal deformity is very complex with many challenges due to its complexity. This study presents the surgical results after correcting a secondary bilateral cleft lip nasal deformity using isolation and repositioning of the lower lateral cartilages, the columellar strut, and an onlay graft on the nasal tip.

Method:
Eighteen patients who had bilateral cleft lip nasal deformities and who had surgery performed between September 2013 and December 2019 were included in this study. The age of the patients ranged between 19 and 52 years. Open rhinoplasty with bilateral reverse-U incision was performed. The lower lateral cartilages were isolated and repositioned. Nasal tip support is provided using a columellar strut with a septal cartilage or Medpor strut. In the vertical component of the nasal tip, a conchal cartilage graft was used. The mean follow-up period was 2 years (ranging from 1 to 6 years).

Results:
Fourteen of the 18 patients underwent photogrammetric evaluation. After surgery, the projection of the nasal tip and angle increased, but nasal bridge length decreased. The columella–labial angle significantly increased by 10.1% after surgery which was statistically significant (P < 0.05). The angle between the nostril axes significantly decreased by 46.2% postoperatively and also reached statistical significance (P < 0.05), indicating that the displaced alar base and lower nostril sill improved and the major axis of the nostril changed more vertically oblique. All patients were pleased with their surgical results.

Conclusion:
The proposed technique was highly effective in correcting secondary bilateral cleft lip nasal deformities in adults.
Forces Exerted in Craniofacial Distraction Osteogenesis
Authors: Kalmar Christopher L. , Wes Ari M. , Mazzaferro Daniel M. , Bartlett Scott P. , Taylor Jesse A. 
Published: October 2021

Background:
The purpose of this study was to develop a methodology for quantifying linear forces of distraction osteogenesis, and thereafter apply this methodology to measure and compare distraction force magnitudes between cranial vault distraction osteogenesis (CVDO) and mandibular distraction osteogenesis (MDO).

Methods:
Patients undergoing CVDO or MDO as inpatients had distraction forces acquired with a digital torque-measuring screwdriver. Torque measurements were then converted into linear distraction force values, which were then compared across distraction types and protocols with appropriate statistics.

Results:
CVDO was performed on 7 patients (41.2%), and MDO was performed on 10 patients (58.8%). Across the entire cohort, the average maximum force per activation was 27.0 N, and the average elastic force was 10.7 N. Maximum force (CVDO: 52.9 N versus MDO: 12.9 N; P < 0.001) and elastic force (CVDO: 22.0 N versus MDO: 4.5 N; P < 0.001) were significantly higher in patients undergoing CVDO than MDO. Multivariate regression demonstrated that maximum activation force was significantly associated with sequential days of distraction (B= + 1.1 N/day; P < 0.001), distraction rate (B= + 8.9 N/mm/day; P = 0.016), distractor hardware failure (B= + 10.3 N if failure; P = 0.004), and distraction type (B= + 41.4 N if CVDO; P < 0.001).

Conclusions:
Cranial vault distraction requires significantly more linear distraction force than mandibular distraction. Maximum forces increase with each day of distraction, as well as with increased distraction rates. Linear distraction force methodology from this study may provide the foundation for future development of optimized procedure-specific or patient-specific distraction protocols.
NBTI attenuates neuroinflammation and apoptosis partly by ENT1/NLRP3/Bcl2 pathway after subarachnoid hemorrhage in rats
Authors: Chen Xiaowei , Luo Xiaocheng , Hu Hang , Xu Qianghua 
Published: October 2021

Objectives
Neuroinflammation and apoptosis are two key factors contributing to early brain injury (EBI) after subarachnoid hemorrhage (SAH) and are strongly associated with a poor prognosis. Recently, equilibrative nucleoside transporter 1 (ENT1) was emerged to accelerate the severity of inflammation and cell apoptosis in several nervous system diseases, including cerebral ischemia, neurodegeneration and epilepsy. However, no study has yet elaborated the expression levels and effects of ENT1 in EBI after SAH.

Methods
Sprague–Dawley rats were subjected to SAH by endovascular perforation. Nitrobenzylthioinosine (NBTI) was intranasally administered at 0.5 h after SAH. The protein expression levels of ENT1, NLRP3, Bcl2, Bax, ACS, Caspase-1, IL-1 were detected by western blot. The modified Garcia score and beam balance score were employed to evaluate the neurologic function of rats following SAH. In addition, hematoxylin-eosin, fluoro-jade C and TdT-mediated dUTP nick-end labeling staining were then used to evaluate brain tissue damage and neuronal apoptosis.

Results
Analysis indicated that endogenous levels of ENT1 were significantly upregulated at 24-hour post-SAH, accompanied by NLRP3 inflammasome activation and Bcl2 decline. The administration of NBTI, an inhibitor of ENT1, at a dose of 15 mg/kg, ameliorated neurologic deficits and morphologic lesions at both 24 and 72 h after SAH. Moreover, ENT1 inhibition efficiently mitigated neuronal degeneration and cell apoptosis. In addition, NBTI at 15 mg/kg observably increased Bcl2 content and decreased Bax level. Furthermore, suppression of ENT1 notably reduced the expression levels of NLRP3, apoptosis associated speck like protein containing CARD, caspase-1 and IL-1β.

Conclusions
NBTI relieved SAH-induced EBI partly through ENT1/NLRP3/Bcl2 pathway.
Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease
Authors: Gong Jiafen , He Gengming , Wang Cheng , Bartlett Claire , Panjwani Naim , Mastromatteo Scott , Lin Fan , Keenan Katherine , Avolio Julie , Halevy Anat , Shaw Michelle , Esmaeili Mohsen , Côté-Maurais Guillaume , Adam Damien , Bégin Stéphanie , Bjornson Candice , Chilvers Mark , Reisman Joe , Price April , Parkins Michael , Van Wylick Richard , Berthiaume Yves , Bilodeau Lara , Mateos-Corral Dimas , Hughes Daniel , Smith Mary J. , Morrison Nancy , Brusky Janna , Tullis Elizabeth , Stephenson Anne L. , Quon Bradley S. , Wilcox Pearce , Leung Winnie M. , Solomon Melinda , Sun Lei , Brochiero Emmanuelle , Moraes Theo J. , Gonska Tanja , Ratjen Felix , Rommens Johanna M. , Strug Lisa J. 
Published: October 2021

AbstractBackgroundOver 400 variants in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) are CF-causing. CFTR modulators target variants to improve lung function, but marked variability in response exists and current therapies do not address all CF-causing variants highlighting unmet needs. Alternative epithelial ion channel/transporters such as SLC26A9 could compensate for CFTR dysfunction, providing therapeutic targets that may benefit all individuals with CF.MethodWe investigate the relationship between rs7512462, a marker ofSLC26A9activity, and lung function pre- and post-treatment with CFTR modulators in Canadian and US CF cohorts, in the general population, and in those with chronic obstructive pulmonary disease (COPD).ResultsRs7512462 CC genotype is associated with greater lung function in CF individuals with minimal function variants (for which there are currently no approved therapies; p=0.008); and for gating (p=0.033) and p.Phe508del/ p.Phe508del (p=0.006) genotypes upon treatment with CFTR modulators. In parallel, human nasal epithelia with CC and p.Phe508del/p.Phe508del after Ussing chamber analysis of a combination of approved and experimental modulator treatments show greater CFTR function (p=0.0022). Beyond CF, rs7512462 is associated with lung function in a meta-analysis of the UK Biobank and Spirometa Consortium (min p=2.74×0-44) and provides p=0.0891 in an analysis of COPD case-control status in the UK Biobank defined by spirometry.ConclusionThese findings support SLC26A9 as a therapeutic target to improve lung function for all people with CF and in individuals with other obstructive lung diseases.
High risk of SARS-CoV-2 infection among frontline healthcare workers in Northeast Brazil: a respondent-driven sampling approach
Authors: Albuquerque Maria de Fátima Pessoa Militão de , de Souza Wayner Vieira , Montarroyos Ulisses Ramos , Pereira Cresio Romeu , Braga Cynthia , de Araújo Thália Velho Barreto , de Alencar Ximenes Ricardo Arraes , de Barros Miranda-Filho Demócrito , Szwarcwald Célia Landmann , de Souza Junior Paulo Roberto Borges , do Nascimento Xavier Morgana , de Morais Clarice Neuenschwander Lins , de Albuquerque Gabriela Diniz Militao , Bresani Salvi Cristiane C. , de Araújo Mariz Carolline , de Siqueira Filha Noêmia Teixeira , Galindo Jadson Mendonça , de França Neto Cláudio Luiz , Barbosa Jessyka Mary Vasconcelos , de Sousa Mascena Veras Maria Amelia , Lima Luana Nepomuceno Gondim Costa , Cruz Luciane Nascimento , Kendall Carl , Kerr Ligia Regina Franco Sansigolo , Martelli Celina Maria Turchi 
Published: October 2021

AbstractIntroductionThe disparities in the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among frontline health care workers (HCWs) and the unique work circumstances are poorly documented for low-and middle-income countries.MethodsWe assessed the frequency of SARS-CoV-2 infection, personal protective equipment (PPE) shortages, PPE use, and accidents involving biological material among HCWs in the Recife metropolitan area, Northeast Brazil. Using respondent driven sampling, we included HCWs attending suspected or confirmed COVID-19 patients from May 2020 to February 2021.ResultsWe analyzed 1,525 HCWs (527 physicians, 471 registered nurses, 263 nursing assistants/technicians, and 264 physical therapists). Women predominated in all categories (81.1%). Nurses were older and had more comorbidities (hypertension and overweight/obesity) than the other HCWs. The overall prevalence of SARS-CoV-2 infection was 61.8% after adjustment for the cluster random effect, weighted by network, and reference population size. The independent risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56), not always using all recommended PPE in routine practice (ORadj: 2.15), and reporting a splash of biological fluid/respiratory secretion in the eyes (ORadj: 3.37).ConclusionsThe high risk of infection among HCWs reflects PPE shortages and younger, possibly less experienced, frontline HCWs. There were disparities in the risk of SARS-CoV-2 infection among HCWs, with nursing assistants being the most vulnerable, possibly due to their longer and frequent contact with COVID-19 patients.
A novel framework based on deep learning and ANOVA feature selection method for diagnosis of COVID-19 cases from chest X-ray Images
Authors: Nasiri Hamid , Alavi Seyyed Ali 
Published: October 2021

AbstractThe new coronavirus (known as COVID-19) was first identified in Wuhan and quickly spread worldwide, wreaking havoc on the economy and people’s everyday lives. Fever, cough, sore throat, headache, exhaustion, muscular aches, and difficulty breathing are all typical symptoms of COVID-19. A reliable detection technique is needed to identify affected individuals and care for them in the early stages of COVID-19 and reduce the virus’s transmission. The most accessible method for COVID-19 identification is RT-PCR; however, due to its time commitment and false-negative results, alternative options must be sought. Indeed, compared to RT-PCR, chest CT scans and chest X-ray images provide superior results. Because of the scarcity and high cost of CT scan equipment, X-ray images are preferable for screening. In this paper, a pre-trained network, DenseNet169, was employed to extract features from X-ray images. Features were chosen by a feature selection method (ANOVA) to reduce computations and time complexity while overcoming the curse of dimensionality to improve predictive accuracy. Finally, selected features were classified by XGBoost. The ChestX-ray8 dataset, which was employed to train and evaluate the proposed method. This method reached 98.72% accuracy for two-class classification (COVID-19, healthy) and 92% accuracy for three-class classification (COVID-19, healthy, pneumonia).
Explainable Transformer-Based Neural Network for the Prediction of Survival Outcomes in Non-Small Cell Lung Cancer (NSCLC)
Authors: Kipkogei Elly , Arango Argoty Gustavo Alonso , Kagiampakis Ioannis , Patra Arijit , Jacob Etai 
Published: October 2021

AbstractIn this paper, we introduce the “Clinical Transformer” - a recasting of the widely used transformer architecture as a method for precision medicine to model relations between molecular and clinical measurements, and the survival of cancer patients. Although the emergence of immunotherapy offers a new hope for cancer patients with dramatic and durable responses having been reported, only a subset of patients demonstrate benefit. Such treatments do not directly target the tumor but recruit the patient’s immune system to fight the disease. Therefore, the response to therapy is more complicated to understand as it is affected by the patient’s physical condition, immune system fitness and the tumor. As in text, where the semantics of a word is dependent on the context of the sentence it belongs to, in immuno-therapy a biomarker may have limited meaning if measured independent of other clinical or molecular features. Hence, we hypothesize that the transformer-inspired model may potentially enable effective modelling of the semantics of different biomarkers with respect to patients’ survival time. Herein, we demonstrate that this approach can offer an attractive alternative to the survival models utilized in current practices as follows: (1) We formulate an embedding strategy applied to molecular and clinical data obtained from the patients. (2) We propose a customized objective function to predict patient survival. (3) We show the applicability of our proposed method to bioinformatics and precision medicine. Applying the clinical transformer to several immuno-oncology clinical studies, we demonstrate how the clinical transformer outperforms other linear and non-linear methods used in current practice for survival prediction. We also show that when initializing the weights of a domain-specific transformer by the weights of a cross-domain transformer, we further improve the predictions. Lastly, we show how the attention mechanism successfully captures some of the known biology behind these therapies.
Predictive value of circulating NMR metabolic biomarkers for type 2 diabetes risk in the UK Biobank study
Authors: Bragg Fiona , Trichia Eirini , Aguilar-Ramirez Diego , Bešević Jelena , Lewington Sarah , Emberson Jonathan 
Published: October 2021

SummaryBackgroundEffective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors.MethodsNMR-metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed.FindingsDuring median 11.9 (IQR 11.1-12.6) years’ follow-up, 1719 participants developed T2D. After accounting for multiple testing, 118 metabolic biomarkers showed independent associations with T2D risk (false discovery rate controlled p<0.05), of which 103 persisted after additional adjustment for HbA1c. Overall, 10 metabolic biomarker PCs were independently associated with T2D. Addition of PCs to the established risk prediction model (including age, sex, parental history of diabetes, body mass index and HbA1c) improved T2D risk prediction as assessed by the c-statistic (increased from 0.802 [95% CI 0.791-0.812] to 0.830 [0.822-0.841]), continuous NRI (0.44 [0.38-0.49]), and relative (15.0% [10.5%-20.4%]) and absolute (1.5 [1.0-1.9]) IDI.InterpretationWhen added to conventional risk factors, circulating NMR-based metabolic biomarkers enhanced T2D risk prediction.FundingBHF, MRC, CRUK
Multi-parameter optical imaging of immune cell activity in chimeric antigen receptor T-cell and checkpoint blockade therapies
Authors: Xie Jinghang , Rami Fadi El , Zhou Kaixiang , Simonetta Federico , Chen Zixin , Zheng Xianchuang , Chen Min , Balakrishnan Preethi B. , Dai Sheng-Yao , Murty Surya , Alam Israt S. , Baker Jeanette , Negrin Robert S. , Gambhir Sanjiv S. , Rao Jianghong 
Published: October 2021

AbstractLongitudinal multimodal imaging presents unique opportunities for noninvasive surveillance and prediction of treatment response to cancer immunotherapy. In this work we first designed a novel granzyme B activated self-assembly small molecule, G-SNAT, for quantitative assessment of cytotoxic T lymphocyte mediated cancer cell killingin vivo. In lymphoma tumor bearing mice, the retention of cyanine 5 labeled G-SNAT-Cy5 was shown to be highly correlated to CAR T-cell mediated granzyme B release and tumor eradication. In colorectal tumor-bearing transgenic mice, expressing firefly luciferase in hematopoietic cells, and which received combination treatment of anti-PD-1 and anti-CTLA-4, longitudinal bioluminescence and fluorescence imaging revealed the dynamics of immune cell expansion, trafficking, tumor infiltration, and cytotoxic activity which predicted therapeutic outcome before tumor shrinkage was evident. These results support further development of G-SNAT for imaging early immune response to checkpoint blockade and CAR T-cell therapy in patients and highlight the utility of multimodality imaging for improved mechanistic insights into cancer immunotherapy.