bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin-like growth factor reduced against decabromodiphenyl ether-209–induced neurodevelopmental toxicity in vivo and in vitro
Authors: Yang Yuanxiang , He Qianyun , Zhang Zhengyu , Qi Chunli , Ding Lina , Yuan Tingting , Chen Yanhong , Li Zhihua 
Published: October 2021

Objective How to reduce the neurodevelopmental toxicity of decabromodiphenyl ether (PBDE-209) remains unclear. This study investigated neurodevelopmental toxicity of PBDE-209 and the protective effects of insulin-like growth factor-1 (IGF-1) Methods Pregnant Sprague–Dawley rats were treated with PBDE-209 and IGF-1, and the offspring were subjected to the Morris Water Maze test. Hippocampal neurons were cultured with PBDE-209 and IGF-1 or the PI3K inhibitor or MEK inhibitor for cell viability, apoptosis, immunofluorescence, and Western blot assays. Results Prenatal PBDE-209 exposure impaired the learning and memory ability of rats by delaying the mean latency to the platform compared, whereas prenatal treatment with IGF-1 treatment improved the learning and memory ability. In vitro, treatment of primary cultured hippocampal neural stem cells (H-NSCs) with PBDE-209 reduced cell proliferation and differentiation, but induced apoptosis. In contrast, IGF-1 treatment antagonized the cytotoxic effects of PBDE-209 in H-NSCs in vitro. At the gene level, IGF-1 inhibition of PBDE-209–induced cell cytotoxicity was through the activation of the PI3K/AKT and MEK/ERK signaling pathways in vitro because the effect of IGF-1 was blocked by the AKT inhibitor LY294002 and the ERK1/2 inhibitor PD98059. Conclusion Prenatal PBDE-209 exposure impaired the learning and memory ability of rats, whereas IGF-1 treatment was able to inhibit the neurodevelopmental toxicity of PBDE-209 by activation of the PI3K/AKT and ERK1/2 cell pathways.
Prognostic Utility of Pretreatment Neutrophil-Lymphocyte Ratio in Advanced Larynx Cancer
Authors: Kotha Nikhil V , Voora Rohith S , Qian Alex S , Kumar Abhishek , Qiao Edmund M , Stewart Tyler F , Rose Brent S , Orosco Ryan K 
Published: October 2021

Purpose: Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent. Methods: In the Veterans Affairs’ (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O’Quigley’s method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. Results: In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54, P = .001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, P < .001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, P = .58). Conclusion: In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population.
Improving self-reported empathy and communication skills through harm in healthcare response training
Authors: Samuels Aimee , Broome Marion E. , McDonald Timothy B. , Peterson Chii-Hui , Thompson Julie A. 
Published: October 2021

Objective Communication and Resolution Programs (CRP) were developed to equip healthcare organizations with tools to respond when physical and psychological harm occurs. Our objective was to assess development of empathic behaviors and communication skills through CRP training based upon the Agency for Healthcare Research and Quality (AHRQ) CANDOR toolkit to assess the ability to develop and improve empathic behaviors and communication skills. Methods The Jefferson Scale of Empathy, the CANDOR Communication Assessment Questionnaire and a self-assessment were used pre- and post-intervention to analyze development of empathy, growth of communication, and improvement in confidence and knowledge through 6 h of virtual education over a six-week course. Results Self-reported communication, confidence and knowledge improved with statistical significance and small to moderate effect size in both men and women. A statistically significant improvement of self-reported empathy scores t (22)  =  2.23, p  =  .037; (95% CI  =  0.41 to 11.5) for women only represented a small to moderate effect size (Cohen’s d  =  0.46). While there was no improvement in Cognitive Complexity, (Cohen’s d  =  0.065) mean pre-post .42 (SD  =  6.52); Message Design Logic improved with statistical significance in paired pre-and post-assessment (Z  =  -3.28, p  =  .001). Notably, previous attendance at CANDOR classes demonstrated no impact on improvement of scores. Conclusions Our findings demonstrate improvement in self-reported empathy and communication skills through harm in healthcare response training. Healthcare organizations should carefully consider investing in CANDOR training for the benefit of patients, their families, and healthcare workforce members.
Calculating the serial interval of SARS-CoV-2 in Lebanon using 2020 contact-tracing data
Authors: Haddad Nadine , Clapham Hannah Eleanor , Abou Naja Hala , Saleh Majd , Farah Zeina , Ghosn Nada , Mrad Pamela , Howard Natasha 
Published: October 2021

Abstract
Introduction
The first detected case in Lebanon on 21 February 2020 engendered implementation of a nationwide lockdown alongside timely contact-tracing and testing.

Objectives
Our study aims to calculate the serial interval of SARS-CoV-2 using contact tracing data collected 21 February to 30 June 2020 in Lebanon to guide testing strategies.

Methods
rRT-PCR positive COVID-19 cases reported to the Ministry of Public Health Epidemiological Surveillance Program (ESU-MOH) are rapidly investigated and identified contacts tested. Positive cases and contacts assigned into chains of transmission during the study time-period were verified to identify those symptomatic, with non-missing date-of-onset and reported source of exposure. Selected cases were classified in infector–infectee pairs. We calculated mean and standard deviation for the serial interval and best distribution fit using AIC criterion.

Results
Of a total 1788 positive cases reported, we included 103 pairs belonging to 24 chains of transmissions. Most cases were Lebanese (98%) and male (63%). All infectees acquired infection locally. Mean serial interval was 5.24 days, with a standard deviation of 3.96 and a range of − 4 to 16 days. Normal distribution was an acceptable fit for our non-truncated data.

Conclusion
Timely investigation and social restriction measures limited recall and reporting biases. Pre-symptomatic transmission up to 4 days prior to symptoms onset was documented among close contacts. Our SI estimates, in line with international literature, provided crucial information that fed into national contact tracing measures. Our study, demonstrating the value of contact-tracing data for evidence-based response planning, can help inform national responses in other countries.
Impact of telemedicine adoption on accessibility and time to treatment in patients with thoracic malignancies during the COVID-19 pandemic
Authors: Nimgaonkar Vivek , Aggarwal Charu , Berman Abigail T. , Gabriel Peter , Shulman Lawrence N. , Kucharczuk John , Roy Megan , Bauml Joshua M. , Singh Aditi P. , Cohen Roger B. , Langer Corey J. , Marmarelis Melina E. 
Published: October 2021

Abstract
Background
To ensure safe delivery of oncologic care during the COVID-19 pandemic, telemedicine has been rapidly adopted. However, little data exist on the impact of telemedicine on quality and accessibility of oncologic care. This study assessed whether conducting an office visit for thoracic oncology patients via telemedicine affected time to treatment initiation and accessibility.

Methods
This was a retrospective cohort study of patients with thoracic malignancies seen by a multidisciplinary team during the first surge of COVID-19 cases in Philadelphia (March 1 to June 30, 2020). Patients with an index visit for a new phase of care, defined as a new diagnosis, local recurrence, or newly discovered metastatic disease, were included.

Results
240 distinct patients with thoracic malignancies were seen: 132 patients (55.0%) were seen initially in-person vs 108 (45.0%) via telemedicine. The majority of visits were for a diagnosis of a new thoracic cancer (87.5%). Among newly diagnosed patients referred to the thoracic oncology team, the median time from referral to initial visit was significantly shorter amongst the patients seen via telemedicine vs. in-person (median 5.0 vs. 6.5 days, p < 0.001). Patients received surgery (32.5%), radiation (24.2%), or systemic therapy (30.4%). Time from initial visit to treatment initiation by modality did not differ by telemedicine vs in-person: surgery (22 vs 16 days, p = 0.47), radiation (27.5 vs 27.5 days, p = 0.86, systemic therapy (15 vs 13 days, p = 0.45).

Conclusions
Rapid adoption of telemedicine allowed timely delivery of oncologic care during the initial surge of the COVID19 pandemic by a thoracic oncology multi-disciplinary clinic.
Associations between body composition and fundamental motor skill competency in children
Authors: Webster E. Kipling , Sur Indica , Stevens Alicia , Robinson Leah E. 
Published: October 2021

AbstractBackgroundEvidence supports an inverse relationship between weight status and motor competence, but most work utilizes body mass index as the proxy for weight status. Body mass index fails to account for essential components of body composition, which may be critical for motor performance. The purpose of this investigation was to examine the relationship between fundamental motor skills competency and body composition (i.e., fat mass, fat percentage, and fatfree mass) as measured by bio-electrical impedance analysis and body mass index in children.MethodsTwo hundred forty-four children from the Southeastern portion of the United States participated in this project (6.05 ± 2.01 years, 53.3% male). Fundamental motor skills were measured using the Test of Gross Motor Development – 2nd edition and body composition was assessed with the Tanita SC-331S Body Composition Analyzer (bio-electrical impedance analysis). Body mass index was calculated using CDC normative growth charts.ResultsBio-electrical impedance analysis measures accounted for 23.1%, F(3, 241) = 24.10,p < .001 and 2.7%, F(3, 241) = 2.22,p = .086 variance in locomotor and object control subscales, respectively; body mass index accounted for 8.4% (locomotor) and 0.1% (object control) variance. For the Test of Gross Motor Development -2nd edition total score, bio-electrical impedance analysis measures accounted for 24.4% F(3, 241) = 25.90,p < .001 compared to body mass index which accounted for 7.9% F(1, 244) = 20.86,p < .001 of the variance. Only fat free mass (p < .001) was a significant predictor for locomotor skills and total models for the Test of Gross Motor Development – 2nd edition; BMI was also a significant predictor (p < .001) in both the locomotor and total models.ConclusionsDifferent components of body composition (i.e., fat free mass) were associated with different aspects of fundamental motor skills competency. Excess body fat may be a morphological constraint to proficient locomotor performance when transporting the body through space. In contrast, body composition did not significantly predict object manipulation performance. More work is needed to understand the causality and directionality of this relationship; however, bio-electrical impedance analysis accounts for more variance in fundamental motor skills performance than body mass index in a field-based setting.
Conjunctival granulomatous capillary haemangioma in children: case report and review of the literature
Authors: Shi Caiping , Ren Yanhong , Feng Jia , Guo Weizhong , Zheng Xiaoyu 
Published: October 2021

Abstract
Background
Granulomatous capillary haemangioma refers to a benign vascular tumour that commonly affects the skin, with occasional involvement of the mucosa. Reports of conjunctival granulomatous capillary haemangioma in children are uncommon. In this article, we present a case of granulomatous capillary haemangioma and a brief review of the relevant literature.

Case presentation
An 11-year-old girl presented with a conjunctival mass. An excision of the entire lesion was performed. Histopathology showed a granulomatous capillary haemangioma.

Conclusions
The clinical manifestations of granulomatous capillary haemangioma lack specificity; pathological characteristics and immunohistochemistry are the main basis for diagnosis. We retrospectively analysed the diagnosis and treatment of a patient with conjunctival granulomatous capillary haemangioma to deepen the understanding and facilitate the diagnosis and treatment of this disease.
Validation of the Arabic Severe Respiratory Insufficiency Questionnaire
Authors: Alawieh Marwan F. , Bzeih Rania N. , El-Khatib Mohamad F. , Sibai Abla M. , Ghandour Lilian A. , Zeineldine Salah M. 
Published: October 2021

Abstract
Background/objectives
Assessment of Health-Related Quality of Life (HRQL) in patients with chronic respiratory insufficiency requiring Home Mechanical Ventilation (HMV) requires a valid measurement tool. The Severe Respiratory Insufficiency (SRI) questionnaire, originally developed in German, has been translated into different languages and tested in different contexts, but has so far not been in use in Arabic-speaking populations. The objective of this study is to validate the Arabic version of the SRI questionnaire in a sample of Arabic-speaking patients from Lebanon.

Methods
Following forward/backward translations, the finalized Arabic version was administered to 149 patients (53 males–96 females, age 69.80 ± 10 years) receiving HMV. Patients were recruited from outpatient clinics and visited at home. The Arabic SRI and the 36-Item Short-Form Health Survey (SF-36) were administered, in addition to questions on sociodemographics and medical history. Exploratory Factor Analysis (EFA) was used to explore dimensionality; internal consistency reliability of the unidimensional scale and its subscales was assessed using Cronbach’s alpha. External nomological validity was examined by assessing the correlation between the SRI and SF-36 scores.

Results
The 49-item Arabic SRI scale showed a high internal consistency reliability (Cronbach alpha for the total scale was 0.897 and ranged between 0.73 and 0.87 for all subscales). Correlations between the SF-36-Mental Health Component MHC and SF-36-Physical Health Component with SRI-Summary Scale were 0.57 and 0.66, respectively, with higher correlations observed between the SF-36 and specific sub-scales such as the Physical Functioning and the Social Functioning subscales [r = 0.81 and r = 0.74 (P < 0.01), respectively].

Conclusion and recommendations
The Arabic SRI is a reliable and valid tool for assessing HRQL in patients with chronic respiratory insufficiency receiving home mechanical ventilation.
Long-term outcomes of transvaginal mesh surgery for pelvic organ prolapse: a retrospective cohort study
Authors: Wang Xiaojuan , Chen Yisong , Hu Changdong , Hua Keqin 
Published: October 2021

Abstract
Background
The objective of this study was to evaluate the overall outcomes and complications of transvaginal mesh (TVM) placement for the management of pelvic organ prolapse (POP) with different meshes with a greater than 10-years of follow-up.

Methods
We performed a retrospective review of patients with POP who underwent prolapse repair surgery with placement of transvaginal mesh (Prolift kit or self-cut Gynemesh) between January 2005 and December 2010. Baseline of patient characteristics were collected from the patients’ medical records. During follow-up, the anatomical outcomes were evaluated using the POP Quantification system, and the Patient Global Impression of Improvement (PGI-I) was used to assess the response of a condition to therapy. Overall postoperative satisfaction was assessed by the following question: “What is your overall postoperative satisfaction, on a scale from 0 to 10?”. Relapse-free survival was analyzed using Kaplan–Meier curves.

Results
In total, 134 patients were included. With a median 12-year (range 10–15) follow-up, 52 patients (38.8%) underwent TVM surgery with Prolift, and Gynemesh was used 82 (61.2%). 91% patients felt that POP symptom improved based on the PGI-I scores, and most satisfied after operation. The recurrence rates of anterior, apical and posterior compartment prolapse were 5.2%, 5.2%, and 2.2%, respectively. No significant differences in POP recurrence, mesh-associated complications and urinary incontinence were noted between TVM surgery with Prolift versus Gynemesh.

Conclusions
Treatment of POP by TVM surgery exhibited long-term effectiveness with acceptable morbidity. The outcomes of the mesh kit were the same as those for self-cutmesh.
Investigating the potential of proton therapy for hypoxia-targeted dose escalation in non-small cell lung cancer
Authors: Köthe Andreas , Bizzocchi Nicola , Safai Sairos , Lomax Antony John , Weber Damien Charles , Fattori Giovanni 
Published: October 2021

Abstract
Background
Hypoxia is known to be prevalent in solid tumors such as non-small cell lung cancer (NSCLC) and reportedly correlates with poor prognostic clinical outcome. PET imaging can provide in-vivo hypoxia measurements to support targeted radiotherapy treatment planning. We explore the potential of proton therapy in performing patient-specific dose escalation and compare it with photon volumetric modulated arc therapy (VMAT).

Methods
Dose escalation has been calibrated to the patient specific tumor response of ten stage IIb-IIIb NSCLC patients by combining HX4-PET imaging and radiobiological modelling of oxygen enhancement ratio (OER) to target variable tumor hypoxia. In a dose-escalation-by-contour approach, escalated dose levels were simulated to the most hypoxic region of the primary target and its effectiveness in improving loco-regional tumor control was assessed. Furthermore, the impact on normal tissue of proton treatments including dose escalation was evaluated in comparison to the normal tissue complication probability (NTCP) of conventional VMAT plans.

Results
Ignoring regions of tumor hypoxia can cause overestimation of TCP values by up to 10%, which can effectively be recovered on average to within 0.9% of the nominal TCP, using patient-specific dose escalations of up to 22% of the prescribed dose to PET defined hypoxic regions. Despite such dose escalations, the use of protons could also simultaneously reduce mean doses to the heart (− 14.3 GyRBE), lung (− 8.3 GyRBE), esophagus (− 6.9 GyRBE) and spinal cord (− 3.8 Gy) compared to non-escalated VMAT plans. These reductions are predicted to lead to clinically relevant decreases in NTCP for radiation-induced pneumonitis (− 11.3%), high grade heart toxicity (− 7.4%) and esophagitis (− 7.5%).

Conclusions
This study suggests that the administration of proton therapy for dose escalation to patient specific regions of tumor hypoxia in the treatment of NSCLC can mitigate TCP reduction due to hypoxia-induced radio resistance, while simultaneously reducing NTCP levels even when compared to non-escalated treatments delivered with state-of-the-art photon techniques.
Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations
Authors: Maiorana Arianna , Caviglia Stefania , Greco Benedetta , Alfieri Paolo , Cumbo Francesca , Campana Carmen , Bernabei Silvia Maria , Cusmai Raffaella , Mosca Antonella , Dionisi-Vici Carlo 
Published: October 2021

Abstract
Background
Hyperinsulinemic hypoglycemia (HI) is the most frequent cause of recurrent hypoglycemia in children. Despite diagnostic and therapeutic advances, it remains an important cause of morbidity, leading to neurological complications, such as psychomotor retardation and epilepsy. Patients with diffuse drug-unresponsive HI manifest neurological impairment and neurobehavioral problems, even though surgically treated with a near-total pancreatectomy. Based on the analogies between HI and GLUT1 deficiency, both presenting with neuroglycopenia and lack of alternative cerebral energy sources, we administered a ketogenic diet (KD) in three drug-unresponsive GCK-HI patients with the aim of preserving neurodevelopment and avoiding the need of a near-total pancreatectomy. They presented recurrent symptomatic hypoglycemia, intellectual disability and refractory epilepsy. Patients were treated with classical KD for 79, 27 and 18 months, respectively.

Results
All patients became asymptomatic in a few days and showed an important improvement of the alert state. Epilepsy disappeared and no appearance of novel hypoglycemic lesions was detected with a brain MRI. Cognitive and adaptive abilities rapidly improved and normalized. IQ rose significantly from 81 to 111 (p = 0.04) in patient 1, from 82 vs 95 (p = 0.04) in patient 2, from 60 to 90 (p = 0.04) in patient 3.

Conclusions
We demonstrated the safety and efficacy of KD in the treatment of drug-unresponsive GCK-HI at a short and long-term. The neuroprotective effects of KD determined the recovery from epilepsy and intellectual disabilities and averted the need of a near-total pancreatectomy. All patients and their families reported an improvement of physical and psychosocial well-being, with a substantial improvement of their quality of life. These results might change the course and the quality of life of these patients and their families, having a relevant impact on human lives. Therefore, KD might be considered the elective treatment in unresponsive forms of GCK-HI.