bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Assessment of National Kidney Allocation Policy Change
Authors: Rohan Vinayak S , Pilch Nicole , McGillicuddy John , White Jared , Lin Angello , Dubay Derek , Taber David J , Baliga Prabhakar K 
Published: April 2022

BACKGROUND:
The new kidney allocation changes with elimination of donor service areas (DSAs) and Organ Procurement and Transplantation Network regions were initiated to improve equity in organ allocation. The aim of this evaluation was to determine the operational, financial, and recipient-related effect of the new allocation system on a large rural transplantation program.

STUDY DESIGN:
A retrospective, cross-sectional analysis of organ offers, allograft outcomes, and attributed costs in a comparative time cohort, before (December 16, 2020 to March 14, 2021) and after (March 15, 2021 to June 13, 2021) the allocation change was performed. Outcomes were limited to adult, solitary, deceased donor kidney transplantations.

RESULTS:
We received 198,881 organ offers from 3,886 organ donors at our transplantation center from December 16, 2020 to June 31, 2021: 87,643 (1,792 organ donors) before the change and 111,238 (2094 organ donors) after the change, for a difference of +23,595 more offers (+302 organ donors). This resulted in 6.5 more organs transplanted vs a predicted loss of 4.9 per month. Local organ offers dropped from 70% to 23%. There was a statistically significantly increase in donor terminal serum creatinine (1.2 ± 0.86 mg/dL vs 2.2 ± 2.3 mg/dL, p < 0.001), kidney donor profile index (KDPI) (39 ± 20 vs 48 ± 22, p = 0.017), cold ischemia time (16 ± 7 hours vs 21 ± 6 hours, p < 0.001), and delayed graft function rates (23% vs 40%, p = 0.020).

CONCLUSION:
The new kidney allocation policy has led to an increase in KDPI of donors with longer cold ischemia time, leading to higher delayed graft function rates. This has resulted in increasing logistical and financial burdens on the system. Implementing large-scale changes in allocation based predominantly on predictive modeling needs to be intensely reassessed during a longer follow up.
Prospective Evaluation of Radar-Localized Reflector–Directed Targeted Axillary Dissection in Node-Positive Breast Cancer Patients after Neoadjuvant Systemic Therapy
Authors: Gallagher Kristalyn K , Iles Kathleen , Kuzmiak Cherie , Louie Raphael , McGuire Kandace P , Ollila David W 
Published: April 2022

BACKGROUND:
This is a prospective, single-institution study to evaluate feasibility and accuracy of radar-localized reflector (RLR)–targeted axillary dissection (TAD) in node-positive breast cancer patients after neoadjuvant systemic therapy (NST).

METHODS:
Patients with biopsy-proven T1–2, N1–3 disease were eligible. Before NST, a marker clip and/or RLR was placed into the positive node. After NST, RLR was inserted if not placed previously. All patients underwent RLR TAD followed by axillary lymph node dissection (ALND). Primary end points of the trial were feasibility of RLR TAD and false negative rate (FNR).

RESULTS:
Between 2017 and 2021, 101 patients with N1–3 disease underwent NST. Five patients withdrew from the study, 1 was ineligible, and there were 9 technical failures, thus our final study cohort comprised 86 patients. RLR TAD was performed with probe guidance and confirmed with intraoperative specimen radiograph. After RLR TAD, ALND was performed. Median number of RLR TAD nodes removed was 2 (range 1–10), and the RLR TAD nodes remained positive in 56 patients. Median number of ALND nodes removed was 18 (range 4-46). Accounting for 9 technical failures, feasibility was 90%. All technical failures occurred with attempted placement of RLR after NST. Feasibility rate was 100% when RLR placement occurred at diagnosis. Of the evaluable 86 patients, RLR TAD accurately predicted axillary status in 83 patients, with FNR of 5.1%.

CONCLUSION:
We demonstrate high accuracy of RLR TAD, especially when RLR is placed before NST. For patients who present with N1–3 disease, this is another step towards axillary surgery de-escalation strategies.
Impact of Cryoablation on Pectus Excavatum Repair in Pediatric Patients
Authors: Clark Rachael A , Jacobson Jillian C , Singhal Amogh , Alder Adam C , Chung Dai H , Pandya Samir R 
Published: April 2022

BACKGROUND:
Minimally invasive repair of pectus excavatum (MIRPE) involves placement of a transthoracic, retrosternal support bar under thoracoscopic guidance. Despite its minimally invasive technical approach, postoperative pain is a significant morbidity that often results in increased length of stay. Multi-modal pain control strategies have been used in the past with limited success. Recently, the use of intraoperative intercostal nerve cryoablation (CA) has been added. In the present study, we aim to evaluate the effects of CA on postoperative pain control, opioid requirements, and perioperative outcomes.

STUDY DESIGN:
A single-center, retrospective chart review of all patients (less than 18 years old) who underwent MIRPE from 2009 to 2020 was performed. CA was started in June 2018. Data collection included demographics, preoperative characteristics, intraoperative findings, and postoperative outcomes. We hypothesized that CA would be associated with improved pain scores, lower doses of total inpatient opioid requirement, and shorter length of stay (LOS).

RESULTS:
One hundred sixty-one patients met inclusion criteria: 75 underwent intraoperative CA and 86 underwent MIRPE without CA (NCA group). CA significantly decreased median LOS from 4 days in NCA to 2 days; the use of CA was the only significant predictor of LOS on linear regression. CA was also associated with decreased total PCA, intravenous opioid, and oral opioid dosages. There was no difference in inpatient pain scores and a slight increase in mean procedure time. However, CA was associated with significantly decreased postoperative complications.

CONCLUSIONS:
The use of cryoablation during MIRPE significantly decreases LOS, perioperative opioid requirements, and postoperative complications, with a minimal increase in operative time. Cryoablation is an effective pain control modality in the surgical management of chest wall deformities in children.
Clinical Factors Predictive of Lymph Node Metastasis in Thyroid Cancer Patients: A Multivariate Analysis
Authors: Zheng Hui , Lai Victoria , Lu Jana , Kang Jin K , Chou Jiling , Burman Kenneth D , Wartofsky Leonard , Rosen Jennifer E 
Published: April 2022

BACKGROUND:
Early-stage thyroid cancers have excellent survival. However, lymph node metastases (LNM) confer a worse prognosis and are not always known preoperatively. Therefore, investigation on the clinical and histological factors predictive of LNM in thyroid cancers was conducted to tailor the extent of surgery and radioactive iodine therapy.

STUDY DESIGN:
Multivariate logistic regressions were performed based on retrospective data from thyroid cancer patients seen between 2013 and 2020 at a single institution.

RESULTS:
Among 913 patients, mean age was 49.4 years, 76.5% were female, 58.3% were White, 21.2% were Black, and 27.9% had LNM. In the multivariate analyses in which the outcome was LNM, White (odds ratio [OR] 1.74, 95% CI 0.98 to 3.15, p = 0.064) and Hispanic patients (OR 2.36, 95% CI 0.97 to 5.77, p = 0.059) trended toward higher risk of LNM compared to Black patients, whereas age (OR 0.98, 95% CI 0.97 to 1.00, p = 0.008) showed protective effect. Tumor size (OR 1.04, 95% CI 1.01 to 1.07, p = 0.007), extrathyroidal extension (OR 2.46, 95% CI 1.53 to 3.97, p < 0.001), lymphovascular invasion (OR 6.30, 95% CI 3.68 to 11.14, p < 0.001), and multifocality (OR 1.47, 95% CI 1.01 to 2.12, p = 0.042) were associated with higher risk of LNM. In another model with outcome as >5 LNM, tumor size (OR 1.07, 95% CI 1.03 to 1.11, p = 0.001), age (OR 0.95, 95% CI 0.93 to 0.97, p < 0.001), extrathyroidal extension (OR 3.20, 95% CI 1.83 to 5.61, p < 0.001), and lymphovascular invasion (OR 6.82, 95% CI 3.87 to 12.17, p < 0.001) remained significant predictors.

CONCLUSION:
Our analyses demonstrated and confirmed that age, tumor size, extrathyroidal extension, and lymphovascular invasion are independent predictors of significant LNM, thereby conferring higher risk of recurrence. Risk of LNM based on these patient characteristics should be considered when planning an operative approach.
Effect of Antibiotic Duration in Emergency General Surgery Patients with Intra-Abdominal Infection Managed with Open vs Closed Abdomen
Authors: Diaz Jose J , Zielinski Martin D , Chipman Amanda M , O’Meara Lindsay , Schroeppel Thomas , Cullinane Daniel , Shoultz Thomas , Barnes Stephen L , May Addison K , Maung Adrian A ,   for the MERIDIAN Study Consortium
Published: April 2022

BACKGROUND:
Data on duration of antibiotics in patients managed with an open abdomen (OA) due to intra-abdominal infection (IAI) are scarce. We hypothesized that patients with IAI managed with OA rather than closed abdomen (CA) would have higher rates of secondary infections (SIs) independent of the duration of the antibiotic treatment.

METHODS:
This was an observational, prospective, multicenter, international study of patients with IAI requiring laparotomy for source control. Demographic and antibiotic duration values were collected. Primary outcomes were SI (surgical site, bloodstream, pneumonia, urinary tract) and mortality. Statistical analysis included ANOVA, chi-square/Fisher’s exact test, and logistic regression.

RESULTS:
Twenty-one centers contributed 752 patients. The average age was 59.6 years, 43.6% were women, and 43.9% were managed with OA. Overall mortality was 16.1%, with higher rates among OA patients (31.6% vs 4.4%, p < 0.001). OA patients had higher Sequential Organ Failure Assessment (4.7 vs 1.8, p < 0.001), American Society of Anesthesiologists Physical Status (3.6 vs 2.7, p < 0.001), and APACHE II scores (16.1 vs 9.4, p < 0.001). The mean duration of antibiotics was 6.5 days (8.0 OA vs 5.4 CA, p < 0.001). A total of 179 (23.8%) patients developed SI (33.1% OA vs 16.8% CA, p < 0.001). Longer antibiotic duration was associated with increased rates of SI: 1 to 2 days, 15.8%; 3 to 5 days, 20.4%; 6 to 14 days, 26.6%; and more than 14 days, 46.8% (p < 0.001).

CONCLUSIONS:
Patients with IAI managed with OA had higher rates of SI and increased mortality compared with CA. A prolonged duration of antibiotics was associated with increased rates of SI. Increased antibiotic duration is not associated with improved outcomes in patients with IAI and OA.
Effect of Quarantine and Reopening Measures on Pediatric Trauma Admissions During the 2019 SARS-CoV2 Virus Pandemic
Authors: Gillory Lauren , Cairo Sarah , Megison Steve , Vinson Lori , Chung Dai H , Ryan Mark L 
Published: April 2022

BACKGROUND:
Several studies have reported decreased trauma admissions and increased physical abuse in children resulting from stay-at-home measures. However, these studies have focused on a limited period after the implementation of lockdown policies. The purpose of this study was to examine the effect of quarantine and reopening initiatives on admissions for varying types of injuries in pediatric patients.

STUDY DESIGN:
Registry data for an urban Level I pediatric trauma center were evaluated from April 1, 2018, to March 30, 2021. A timeline of local shutdown and reopening measures was established and used to partition the data into 6-month intervals. Data about demographics and injury characteristics were compared with similar intervals in 2018 and 2019 using appropriate statistical methodology for categorical, parametric, and nonparametric data.

RESULTS:
A total of 3,110 patients met criteria for inclusion. A total of 1,106 patients were admitted the year after the closure of schools and nonessential businesses. Decreases in overall admissions and evaluations for suspected child abuse noted early in the pandemic were not sustained during shutdown or reopening periods. However, we observed a 77% increase in all-terrain vehicle injuries, along with a 59% reduction in sports injuries (chi-square [8, N = 3,110] = 49.7; p < 0.001). Significant shifts in demographic and payor status were also noted.

CONCLUSIONS:
This is the first study to comprehensively examine the effects of quarantine and reopening policies on admission patterns for a pediatric trauma center in a metropolitan area. Total admissions and child abuse evaluations were not impacted. If shutdown measures are re-instituted, preventative efforts should be directed towards ATV use and recreational activities.
Identification of novel microcephaly-linked protein ABBA that mediates cortical progenitor cell division and corticogenesis through NEDD9-RhoA
Authors: Carabalona Aurelie , Kallo Henna , Gonzalez Maryanne , Andriichuk Liliia , Elomaa Ellinoora , Molinari Florence , Fragkou Christiana , Lappalainen Pekka , Wessels Marja W , Saarikangas Juha , Rivera Claudio 
Published: April 2022

AbstractThe cerebral cortex, which is responsible for higher cognitive functions, relies on the coordinated asymmetric division cycles of polarized radial glial progenitor cells for proper development. Defects in the mitotic process of neuronal stem cells have been linked to the underlying causes of microcephaly; however, the exact mechanisms involved are not fully understood. In this study, we present a new discovery regarding the role of the membrane-deforming cytoskeletal regulator protein called Abba (also known as MTSS1L/MTSS2) in cortical development. When Abba was absent in the developing brain, it led to a halt in radial glial cell proliferation, disorganized radial fibers, and abnormal migration of neuronal progenitors. During cell division, Abba localized to the cleavage furrow, where it recruited the scaffolding protein Nedd9, and positively influenced the activity of RhoA, a crucial regulator of cell division. Notably, we identified a variant of Abba (R671W) in a patient with microcephaly and intellectual disability, further highlighting its significance. The introduction of this mutant Abba protein in mice resulted in phenotypic similarities to the effects of Abba knockdown. Overall, these findings offer valuable mechanistic insights into the development of microcephaly and the cerebral cortex by identifying Abba as a novel regulator involved in ensuring the accurate progression of mitosis in neuronal progenitor cells.
Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections
Authors: Kratochvil Michael J. , Kaber Gernot , Demirdjian Sally , Cai Pamela C. , Burgener Elizabeth B. , Nagy Nadine , Barlow Graham L. , Popescu Medeea , Nicolls Mark R. , Ozawa Michael G. , Regula Donald P. , Pacheco-Navarro Ana E. , Yang Samuel , de Jesus Perez Vinicio A. , Karmouty-Quintana Harry , Peters Andrew M. , Zhao Bihong , Buja Maximilian L. , Johnson Pamela Y. , Vernon Robert B. , Wight Thomas N. ,   Stanford COVID-19 Biobank Study Group, Milla Carlos E. , Rogers Angela J. , Spakowitz Andrew J. , Heilshorn Sarah C. , Bollyky Paul L. 
Published: April 2022

AbstractThick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We find the percent solids and protein content are greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factor–stimulated gene-6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID-19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID-19 infection.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is mediated by a stereotyped clonotypic antibody
Authors: Wang Jing Jing , Armour Bridie , Chataway Tim , Troelnikov Alexander , Colella Alex , Yacoub Olivia , Hockley Simon , Tan Chee Wee , Gordon Tom Paul 
Published: April 2022

ABSTRACTVaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare thromboembolic complication of adenoviral-vectored SARS-CoV2 vaccines, mediated by antibodies directed against platelet factor 4 (PF4). Given their causal role in VITT, identification of the molecular composition of anti-PF4 antibodies is crucial for developing better diagnostics and treatments. Here, we utilised a novel proteomic workflow to analyse the immunoglobulin variable (IgV) region composition of anti-PF4 antibodies at the level of the secreted proteome. Serum anti-PF4 IgG antibodies from five patients with VITT triggered by ChAdOx1 nCoV-19 vaccination were affinity purified by PF4-coupled magnetic beads and sequenced by mass spectrometry. We revealed a single IgG heavy (H)-chain species paired with a single lambda light (L)-chain species in all five unrelated patients. Remarkably, all L-chains were encoded by the identical IGLV3-21*02 gene subfamily with identical L-chain third complementarity determining region (LCDR3) lengths. Moreover, striking stereotypic features were also identified in heavy-chains anti-PF4 antibodies characterised by identical HCDR3 length and homologous sequences. In summary, we unravelled the molecular signature of highly stereotyped clonotypic anti-PF4 antibodies, indicating shared pathways of antibody production in VITT patients. These discoveries are critical to understand the molecular basis of this serious condition and develop novel therapies aimed at removing pathogenic clones.KEY POINTSAnti-PF4 antibodies in VITT comprise highly stereotyped clonotypeA single IGLV3-21*02 encoded light chain is found in unrelated patients
A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation
Authors: Poppelaars Felix , Eskandari Siawosh K. , Damman Jeffrey , Seelen Marc A. , Faria Bernardo , da Costa Mariana Gaya 
Published: April 2022

AbstractBackgroundDespite current matching efforts to identify optimal donor-recipient pairs in kidney transplantation, alloimmunity remains a major proponent of late transplant failure. While kidney allocation based on human leukocyte antigen (HLA) matching has markedly prolonged short-term graft survival, new data suggests that additional genetic parameters in donor-recipient matching could help improve the long-term outcomes. Here, we studied the impact of a recently discovered non-muscle myosin heavy chain 9 gene (MYH9) polymorphism on kidney allograft failure.MethodsWe conducted a prospective observational cohort study, analyzing the DNA of 1,271 kidney donor-recipient transplant pairs from a single academic hospital for the MYH9 rs11089788 C>A polymorphism. The association of the MYH9 genotype with the risk of graft failure (primary outcome), biopsy-proven acute rejection (BPAR), and delayed graft function (DGF) (secondary outcomes) were determined.ResultsThe MYH9 polymorphism in the donor was not associated with 15-year death-censored kidney graft survival, whereas a trend was seen for the association between the MYH9 polymorphism in the recipient and graft failure (recessive model, P=0.056). Having the AA-genotype of the MYH9 polymorphism in recipients was associated with a higher risk of DGF (P=0.031) and BPAR (P=0.021), although the significance was lost after adjustment for potential confounders (P=0.15 and P=0.10, respectively). The combined presence of the MYH9 polymorphism in donor-recipient pairs was significantly associated with long-term kidney allograft survival (P=0.036), in which recipients with an AA-genotype receiving a graft with an AA-genotype had the worst outcome. After adjustment for covariates, this combined genotype remained significantly associated with 15-year death-censored kidney graft survival (HR 1.68, 95%-CI: 1.05 – 2.70, P=0.031).ConclusionsOur results reveal that recipients with an AA-genotype MYH9 polymorphism receiving a donor kidney with an AA-genotype, have a significantly elevated risk of graft failure after kidney transplantation.Key pointsIn recipients, the MYH9 SNP was associated with delayed graft function and biopsy-proven acute rejection after kidney transplantation, although the significance was lost in multivariable analysis.Presence of the MYH9 variant in both the donor and recipient significantly associated with long-term kidney allograft survival in multivariable analysis.Our present findings suggests that matching donor-recipient transplant pairs based on the MYH9 polymorphism may attenuate the risk of graft loss.
Estimating the impact of the wMel release program on dengue and chikungunya incidence in Rio de Janeiro, Brazil
Authors: Ribeiro dos Santos Gabriel , Durovni Betina , Saraceni Valeria , Souza Riback Thais Irene , Pinto Sofia B. , Anders Katherine L. , Moreira Luciano A. , Salje Henrik 
Published: April 2022

BackgroundIntrogression of the insect bacterium Wolbachia into Aedes aegypti mosquito populations been shown in randomised and non-randomised trials to reduce the incidence of dengue in treated communities, however evidence for the real-world effectiveness of large-scale Wolbachia mosquito deployments for arboviral disease control in endemic settings is still limited and no effectiveness studies have been conducted for chikungunya virus. A large Wolbachia (wMel strain) program was implemented in 2017 in Rio de Janeiro, Brazil. Here we assess the impact of the release program on dengue and chikungunya incidence.Methods and findingsThe program released 67 million wMel infected mosquitoes across 28,489 release locations over a 86.8km2 area in Rio de Janeiro between August 2017 and the end of 2019. Following releases, mosquitoes were trapped and the presence of wMel determined. To assess the impact of the release program on dengue and chikungunya incidence, we used spatiotemporally explicit models applied to geocoded dengue (N=194,330) and chikungunya cases (N=58,364) from 2010 (2016 for chikungunya) to 2019 from across the city. On average, 32% of mosquitoes collected from the release zones between 1 and 29 months after releases were positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods when dengue and chikungunya cases were historically high. Despite incomplete introgression, we found that the releases were associated with a 38% (95%CI: 32-44%) reduction in dengue incidence and a 10% (95%CI: 4-16%) reduction in chikungunya incidence.ConclusionsStable establishment of wMel in this diverse, urban setting appears more complicated than has been observed elsewhere. However, even intermediate levels of wMel appear to reduce the incidence of two different arboviruses.