bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity of Accompanying Phenotypes and Genomic Variants Involved in Microtia
Authors: Huang Xin , Si Nuo , Guo Peipei , Wang Changchen , Hu Zhensheng , Pan Bo 
Published: July 2021

Objectives:
The symptoms associated with microtia are ever-changing and not to stick to 1 pattern. The symptoms associated with microtia are constantly changing and are not set in stone. The aim of this article was to describe the various phenotypes from multiple systems found in microtitis patients included in the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources database, and to analyze possible pathogenic mutations.

Methods:
DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources is an interactive web-based database, which incorporates a suite of tools designed to aid the interpretation of genomic variants. The term “microtia” was used as the search term, and the data extracted from the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources for this study was updated until October 2020. Pearson chi-squared test was used to test associations between types of genomic variants and the pathogenicity of variants.

Results:
Of the 386 cases enrolled in the study, 99% (n = 382) had 1 or more associated abnormalities. The most frequently detected abnormalities were those of the face and neck (n = 362 [93.8% of all cases]); musculoskeletal system (n = 337 [87.3%]); and nervous system (n = 334 [86.5%]), followed by abnormalities of limbs (n = 252 [65.3%]); the eye (n = 212 [54.9%]); and the integument (n = 200 [51.8%]). Besides, a total of 479 genomic variants were determined, including sequence variants and copy number variants (loss and gain). The pathogenicity of loss-type variants was significantly higher among other types (P < 0.001). Twelve sharing variants had more than 5 repeats, and the repeated fragments were concentrated on chromosome 3, 7, 9, 10, 11, 15, 17, 18, and 22.

Conclusions:
Identification of the relation between phenotypes and genotypes will facilitate the uncovering of the mechanism of microtia and the study of potential therapeutic targets.
Efficacy and Safety of Migraine Surgery
Authors: ElHawary Hassan , Barone Natasha , Baradaran Aslan , Janis Jeffrey E. 
Published: July 2021

Objective:
The objectives of this study are to assess the efficacy and safety of peripheral nerve surgery for migraine headaches and to bibliometrically analyze all anatomical studies relevant to migraine surgery.

Summary Background Data:
Migraines rank as the second leading cause of disability worldwide. Despite the availability of conservative management options, individuals suffer from refractive migraines which are associated with poor quality of life. Migraine surgery, defined as the peripheral nerve decompression/trigger site deactivation, is a relatively novel treatment strategy for refractory migraines.

Methods:
EMBASE and the National Library of Medicine (PubMed) were systematically searched for relevant articles according to the PRISMA guidelines. Data was extracted from studies which met the inclusion criteria. Pooled analyses were performed to assess complication rates. Meta-analyses were run using the random effects model for overall effects and within subgroup fixed-effect models were used.

Results:
A total of 68 studies (38 clinical, 30 anatomical) were included in this review. There was a significant overall reduction in migraine intensity (P < 0.001, SE = 0.22, I
2 = 97.9), frequency (P < 0.001, SE = 0.17, I
2 = 97.7), duration (P < 0.001, SE = 0.15, I
2 = 97), and migraine headache index (MHI, P < 0.001, SE = 0.19, I
2 = 97.2) at follow-up. A total of 35 studies reported on migraine improvement (range: 68.3%–100% of participants) and migraine elimination (range: 8.3%–86.5% of participants). 32.1% of participants in the clinical studies reported complications for which the most commonly reported complications being paresthesia and numbness, which was mostly transient, (12.11%) and itching (4.89%).

Conclusion:
This study demonstrates improved migraine outcomes and an overall decrease in MHI as well as strong evidence for the safety profile and complication rate of migraine surgery.
“I Prefer to Stay Away”: A Qualitative Study of Patients in an Opioid-Sparing Pain Management Protocol
Authors: Johnson Emily , Yoshida Maxwell , Hallway Alexander , Byrnes Mary , Waljee Jennifer , Englesbe Michael , Howard Ryan 
Published: July 2021

Objective:
The aim of this study was to explore beliefs and behaviors of opioid pain medications among patients undergoing elective surgery.

Background:
Opioid dependence after surgery is a major contributor to the ongoing opioid epidemic. Recent efforts by surgeons and health systems have sought to improve the education patients receive regarding safe opioid use after surgery; however, little is known about patients’ pre-existing beliefs surrounding opioids.

Methods:
Semistructured interviews were conducted with patients who underwent 1 of 4 common elective surgical procedures at 1 institution. Patients were specifically asked about their knowledge and beliefs about opioids before surgery and their opinions of opioid-sparing recovery after surgery. Coding was conducted through iterative steps, beginning with an initial cycle of rapid analysis, followed by focused coding, and thematic analysis.

Results:
Twenty-one patients were interviewed. Three major themes emerged regarding patient opinions about using opioids after surgery. First, there was widespread awareness among patients about opioid medications, and preoperatively, patients had specific intentions about using opioids, often informed by this awareness. Second, patients described a spectrum of opioid related behavior which both aligned and conflicted with preoperative intentions. Third, there was tension among patients about opioid-free postoperative recovery, with patients expressing support, opposition, and emphasis on tailoring recovery to patient needs.

Conclusions:
Patients undergoing common surgical procedures often arrive at their surgical encounter with strong, pre-formed opinions about opioids. Eliciting these preexisting opinions may help surgeons better counsel patients about safe opioid use after surgery.
Rural Disparities in Lung Cancer-directed Surgery
Authors: Loehrer Andrew P. , Chen Louisa , Wang Qianfei , Colla Carrie H. , Wong Sandra L. 
Published: July 2021

Objective:
The primary objective of this study was to determine the influence of rural residence on access to and outcomes of lung cancer-directed surgery for Medicare beneficiaries.

Summary of Background Data:
Lung cancer is the leading cause of cancerrelated death in the United States and rural patients have 20% higher mortality. Drivers of rural disparities along the continuum of lung cancercare delivery are poorly understood.

Methods:
Medicare claims (2015–2018) were used to identify 126,352 older adults with an incident diagnosis of nonmetastatic lung cancer. Rural Urban Commuting Area codes were used to define metropolitan, micropolitan, small town, and rural site of residence. Multivariable logistic regression models evaluated influence of place of residence on 1) receipt of cancer-directed surgery, 2) time from diagnosis to surgery, and 3) postoperative outcomes.

Results:
Metropolitan beneficiaries had higher rate of cancer-directed surgery (22.1%) than micropolitan (18.7%), small town (17.5%), and isolated rural (17.8%) (P < 0.001). Compared to patients from metropolitan areas, there were longer times from diagnosis to surgery for patients living in micropolitan, small, and rural communities. Multivariable models found nonmetropolitan residence to be associated with lower odds of receiving cancer-directed surgery and MIS. Nonmetropolitan residence was associated with higher odds of having postoperative emergency department visits.

Conclusions:
Residence in nonmetropolitan areas is associated with lower probability of cancer-directed surgery, increased time to surgery, decreased use of MIS, and increased postoperative ED visits. Attention to timely access to surgery and coordination of postoperative care for nonmetropolitan patients could improve care delivery.
FLOT-regimen Chemotherapy and Transthoracic en bloc Resection for Esophageal and Junctional Adenocarcinoma
Authors: Donlon Noel E. , Kammili Anitha , Roopnarinesingh Ryan , Davern Maria , Power Robert , King Sinead , Chmelo Jakub , Phillips Alexander W. , Donohoe Claire L. , Ravi Narayanasamy , Lowery Maeve , Mueller Carmen L. , Cools-Lartigue Jonathan , Ferri Lorenzo E. , Reynolds John V. 
Published: July 2021

Background and Aims:
The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes.

Study design:
An observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre and post FLOT assessment of sarcopenia and pulmonary physiology.

Results:
175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (P = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34% + 25%; P < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%.

Conclusion:
FLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway.
Medicare Advantage Networks and Access to High-volume Cancer Surgery Hospitals
Authors: Raoof Mustafa , Jacobson Gretchen , Fong Yuman 
Published: July 2021

Objective:
To determine how Medicare Advantage (MA) health plan networks impact access to high-volume hospitals for cancer surgery.

Background:
Cancer surgery at high-volume hospitals is associated with better short- and long-term outcomes. In the United States, health insurance is a major detriment to seeking care at high-volume hospitals. A third of older (>65 years) Americans are enrolled in privatized MA health plans. The impact of MA plan networks on access to high-volume surgery hospitals is unknown.

Methods:
We analyzed in-network hospitals for MA plans offered in Los Angeles county during open enrollment of 2015. For the purposes of this analysis, MA network data from provider directories were linked to hospital volume data from California Office of Statewide Health Planning and Development. Volume thresholds were based on published literature.

Results:
A total of 34 MA plans enrolled 554,754 beneficiaries in Los Angeles county during 2014 open enrollment for coverage starting in 2015 (MA penetration ∼43%). The proportion of MA plans that included high-volume cancer surgery hospital varied by the type of cancer surgery. While most plans (>71%) included at least one high-volume hospital for colon, rectum, lung, and stomach; 59% to 82% of MA plans did not include any high-volume hospitals for liver, esophagus, or pancreatic surgery. A significant proportion of beneficiaries in MA plans did not have access to high-volume hospitals for esophagus (93%), stomach (44%), liver (39%), or pancreas (70%) surgery. In contrast, nearly all MA beneficiaries had access to at least one high-volume hospital for lung (93%), colon (100%), or rectal (100%) surgery. Overall, Centers for Medicare & Medicaid Services plan rating or plan popularity were not correlated with access to high-volume hospital (P > 0.05).

Conclusions:
The study identifies lack of high-volume hospital coverage in MA health plans as a major detriment in regionalization of cancer surgery impacting at least a third of older Americans.
Kidney Transplantation Confers Survival Benefit for Candidates With Pulmonary Hypertension
Authors: Nguyen Michelle C. , Po-Yu Chiang Teresa , Massie Allan B. , Bae Sunjae , Motter Jennifer D. , Brennan Daniel C. , Desai Niraj M. , Segev Dorry L. , Garonzik-Wang Jacqueline M. 
Published: July 2021

Background.
Kidney transplantation (KT) is controversial in patients with pretransplant pulmonary hypertension (PtPH). We aimed to quantify post-KT graft and patient survival as well as survival benefit in recipients with PtPH.

Methods.
Using UR Renal Data System (2000–2018), we studied 90 819 adult KT recipients. Delayed graft function, death-censored graft failure, and mortality were compared between recipients with and without PtPH using inverse probability weighted logistic and Cox regression. Survival benefit of KT was determined using stochastic matching and stabilized inverse probability treatment Cox regression.

Results.
Among 90 819 KT recipients, 2641 (2.9%) had PtPH. PtPH was associated with higher risk of delayed graft function (odds ratio, 1.23; 95% CI, 1.10-1.36; P < 0.01), death-censored graft failure (hazard ratio [HR], 1.23; 95% CI, 1.11-1.38; P < 0.01), and mortality (HR, 1.56; 95% CI, 1.44-1.69; P < 0.01). However, patients with PtPH who received a KT had a 46% reduction in mortality (HR, 0.54; 95% CI, 0.48-0.61; P < 0.01) compared with those who remained on the waitlist.

Conclusions.
Although PtPH is associated with inferior post-KT outcomes, KT is associated with better survival compared with remaining on the waitlist. Therefore, KT is a viable treatment modality for appropriately selected patients with PtPH.
Liberal Use of Interposition Grafts for Arterial Reconstruction Is Safe and Effective in Adult Split Liver Transplantation
Authors: Lau Ngee-Soon , Liu Ken , Almoflihi Abdullah , Xu Josephine , McCaughan Geoffrey , Crawford Michael , Pulitano Carlo 
Published: July 2021

Background.
Split liver transplantation (SLT) addresses donor shortages by providing 2 partial grafts from a single donor liver. Arterial reconstruction using an interposition graft facilitates the use of split grafts with difficult recipient anatomy. Its use, however, remains controversial because of a reported increased risk of complications.

Methods.
A retrospective review of the prospectively maintained Australian National Liver Transplantation Unit database was performed. Donor, recipient, operative, and complications data for adults receiving an SLT between July 2002 and November 2019 were extracted.

Results.
Arterial reconstruction required an interposition graft in 46 of 155 patients. Overall graft and patient survival were not significantly different between the groups with 1-, 3-, and 5-y graft survivals of 82%, 77%, and 69% for those with interposition grafts and 86%, 79%, and 77% for those without interposition grafts, respectively (P = 0.499). There were more cut liver bile leaks in the interposition graft group (26% versus 9%, P = 0.004), but otherwise, no significant differences in the rate of biliary complications (39% versus 29% P = 0.200), hepatic artery thrombosis (7% versus 10%, P = 0.545), or hepatic artery stenosis (13% versus 10%, P = 0.518).

Conclusions.
Liberal use of interposition grafts for arterial reconstruction in SLT is safe and does not result in increased complications.
Engaging Diverse Older Adults With Cognitive Impairment and Caregivers in Advance Care Planning
Authors: Kotwal Ashwin A. , Barnes Deborah E. , Volow Aiesha M. , Li Brookelle H. , Boscardin W. John , Sudore Rebecca L. 
Published: July 2021

Introduction:
Engaging patients with cognitive impairment in advance care planning (ACP), including completing advance directives and naming health care proxies, before they lose decision-making capacity is important.

Methods:
We determined the feasibility of the PREPAREforYourCare.org ACP program among 20 diverse older adults with mild-to-moderate cognitive impairment and their caregivers in a 1-week, pre-post pilot. We examined ease-of-use, satisfaction, and feasibility using validated scales, and change in ACP Engagement scores, including knowledge, contemplation, self-efficacy, and readiness subscales (5-point scales), from baseline to 1-week.

Results:
Participants were on average 70 years old (SD=9.0), 45% Spanish-speaking, 60% had limited health literacy, and 15% felt comfortable using the internet. Patients and caregivers rated PREPARE a mean of 8.6 (SD=1.6) and 9.4 (SD=1.1) on the 10-point ease-of-use scale, 4.7 (SD=0.4) and 4.7 (SD=0.3) on the 5-point satisfaction scale, and 4.9 (SD=0.4) and 4.8 (SD=0.6) on the 5-point feasibility scale, respectively. ACP engagement scores increased for 16 of 20 (80%) patients (P=0.03) and 16 of 20 (80%) caregivers (P=0.18). Caregivers experienced increased knowledge (3.8 to 4.7, P=0.002) and self-efficacy (3.6 to 4.5, P=0.034) for ACP.

Discussion:
The PREPARE website was feasible and may facilitate ACP engagement among diverse older adults with cognitive impairment and their caregivers.
Advances in the treatment of neuropathic pain
Authors: Attal Nadine , Bouhassira Didier 
Published: July 2021

Purpose of review
Neuropathic pain remains difficult to treat. This review provides an update regarding recent advances in therapeutic management, particularly with regards to newer drugs, neurostimulation techniques and original study designs.

Recent findings
Although the mainstay of neuropathic pain management is still represented by drug therapy, particularly antidepressants and antiepileptics, the place of nonpharmacological therapy including in particular brain neuromodulation techniques has substantially increased in recent years. Newer study designs are also increasingly implemented, based on in depth phenotypic profiling to achieve more individualized therapy, or on screening strategies to decrease placebo effect and contribute to increase assay sensitivity. These approaches are now considered the most promising to decrease therapeutic failures in neuropathic pain.

Summary
Neuropathic pain management should not be restricted to pharmacotherapy but now encompasses multiple approaches including particularly neuromodulation techniques. Multimodal assessment can also help identify predictors of the response in clinical trials in order to ensure appropriate management.
Cross-Sectional Analysis of Baseline Visual Parameters in Subjects Recruited Into the RESCUE and REVERSE ND4-LHON Gene Therapy Studies
Authors: Moster Mark L. , Sergott Robert C. , Newman Nancy J. , Yu-Wai-Man Patrick , Carelli Valerio , Bryan Molly Scannell , Smits Gerard , Biousse Valérie , Vignal-Clermont Catherine , Klopstock Thomas , Sadun Alfredo A. , DeBusk Adam A. , Carbonelli Michele , Hage Rabih , Priglinger Siegfried , Karanjia Rustum , Blouin Laure , Taiel Magali , Katz Barrett , Sahel José Alain ,   for the LHON study group
Published: July 2021

Objective:
This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.

Methods:
RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE. Functional visual parameters (best-corrected visual acuity [BCVA], contrast sensitivity [CS], and Humphrey Visual Field [HVF]) and structural parameters assessed by spectral-domain optical coherence tomography were analyzed in both cohorts before treatment. The cross-sectional analysis of functional and anatomic parameters included the baseline values collected in all eyes at 2 different visits (Screening and Inclusion).

Results:
Seventy-six subjects were included in total, 39 in RESCUE and 37 in REVERSE. Mean BCVA was significantly worse in RESCUE subjects compared with REVERSE subjects (1.29 and 1.61 LogMAR respectively, P = 0.0029). Similarly, mean CS and HVF were significantly more impaired in REVERSE vs RESCUE subjects (P < 0.005). The cross-sectional analysis showed that the monthly decrease in BCVA, ganglion cell layer macular volume, and retinal nerve fiber layer thickness was much more pronounced in the first 6 months after onset (+0.24 LogMAR, −0.06 mm3, and −6.00 μm respectively) than between 6 and 12 months after onset (+0.02 LogMAR, −0.01 mm3, and −0.43 μm respectively).

Conclusion:
LHON progresses rapidly in the first months following onset during the subacute phase, followed by relative stabilization during the dynamic phase.
A community-based approach to image analysis of cells, tissues and tumors
Authors:   CSBC/PS-ON Image Analysis Working Group, Vizcarra Juan Carlos , Burlingame Erik A. , Hug Clemens B. , Goltsev Yury , White Brian S. , Tyson Darren R. , Sokolov Artem 
Published: July 2021

AbstractEmerging multiplexed imaging platforms provide an unprecedented view of an increasing number of molecular markers at subcellular resolution and the dynamic evolution of tumor cellular composition. As such, they are capable of elucidating cell-to-cell interactions within the tumor microenvironment that impact clinical outcome and therapeutic response. However, the rapid development of these platforms has far outpaced the computational methods for processing and analyzing the data they generate. While being technologically disparate, all imaging assays share many computational requirements for post-collection data processing. We convened a workshop to characterize these shared computational challenges and a follow-up hackathon to implement solutions for a selected subset of them. Here, we delineate these areas that reflect major axes of research within the field, including image registration, segmentation of cells and subcellular structures, and identification of cell types from their morphology. We further describe the logistical organization of these events, believing our lessons learned can aid others in uniting the imaging community around self-identified topics of mutual interest, in designing and implementing operational procedures to address those topics and in mitigating issues inherent in image analysis (e.g., sharing exemplar images of large datasets and disseminating baseline solutions to hackathon challenges through open-source code repositories).