bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID-19 Pandemic on Liver Cancer Staging at a Multidisciplinary Liver Cancer Clinic
Authors: Li Daniel , Jia Angela Y. , Zorzi Jane , Griffith Paige , Kim Amy K. , Dao Doan , Anders Robert A. , Georgiades Christos , Liddell Robert P. , Hong Kelvin , Azad Nilofer S. , Ho Won Jin , Baretti Marina , Christenson Eric , Baghdadi Azarakhsh , Kamel Ihab R. , Meyer Jeffrey , Ghabi Elie , Burkhart Richard A. , Lafaro Kelly , He Jin , Shubert Chris , Yarchoan Mark 
Published: October 2022

Objectives:
To compare liver cancer resectability rates before and during the COVID-19 pandemic.

Background:
Liver cancers usually present with nonspecific symptoms or are diagnosed through screening programs for at-risk patients, and early detection can improve patient outcomes. In 2020, the COVID-19 pandemic upended medical care across all specialties, but whether the pandemic was associated with delays in liver cancer diagnosis is not known.

Methods:
We performed a retrospective review of all patients evaluated at the Johns Hopkins Multidisciplinary Liver Cancer Clinic from January 2019 to June 2021 with a new diagnosis of suspected or confirmed hepatocellular carcinoma (HCC) or biliary tract cancer (BTC).

Results:
There were 456 liver cancer patients (258 HCC and 198 BTC). From January 2019 to March 2020 (pre-pandemic), the surgical resectability rate was 20%. The subsequent 6 months (early pandemic), the resectability rate decreased to 11%. Afterward from October 2020 to June 2021 (late pandemic), the resectability rate increased to 27%. The resectability rate early pandemic was significantly lower than that for pre-pandemic and later pandemic combined (11% lower; 95% confidence interval [CI], 2%–20%). There was no significant difference in resectability rates pre-pandemic and later pandemic (7% difference; 95% CI, –3% to 16%). In subgroup analyses, the early pandemic was associated with a larger impact in BTC resectability rates than HCC resectability rates. Time from BTC symptom onset until Multidisciplinary Liver Clinic evaluation increased by over 6 weeks early pandemic versus pre-pandemic (Hazard Ratio, 0.63; 95% CI, 0.44–0.91).

Conclusions:
During the early COVID-19 pandemic, we observed a drop in the percentage of patients presenting with curable liver cancers. This may reflect delays in liver cancer diagnosis and contribute to excess mortality related to the COVID-19 pandemic.
Risk Factors of Flexor Tendon Rupture After ORIF of Distal Radius Fracture
Authors: Kwon Young Woo , Choi In Cheul , Kim Myongwhan , Nam Jae Jun , Park Jong Woong 
Published: October 2022

Objectives:
To analyze the risk factors associated with postoperative flexor tendon rupture, after a volar plate fixation of distal radius fractures.

Design:
Retrospective observational case–control study.

Setting:
Tertiary Care University Hospital in the Republic of Korea (2009–2020).

Patients:
Sixteen referred patients were treated for flexor tendon rupture, following previously performed volar plating of distal radius fractures at other institutions. 16 patients were randomly selected from our database as controls, and were matched based on the Soong grade of the case group.

Intervention:
Not applicable.

Main Outcome Measurements:
Radial tilt and radial height were measured on anteroposterior radiographs. The volar tilt, tear drop angle, carpal translation, and Soong grade were measured in a lateral view.

Results:
Quantitative measurements of the volar tilt, carpal translation, and tear drop angle were positively correlated with the flexor tendon rupture. The mean volar tilt and tear drop angle in the tendon rupture group were significantly smaller than those in the control group. The mean carpal translation in the tendon rupture group was significantly greater than that in the control group.

Conclusions:
This study demonstrated that volar tilt, carpal translation, and tear drop angle are significant risk factors for flexor tendon rupture, especially for plates placed at Soong grade 1 or 2. We suggest that the potential for tendon rupture because of incomplete reduction of the distal radius fracture along with implant prominence volar to the watershed line aggravates flexor tendon irritation at the distal edge of the plate because of distorted flexor tendon paths.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Posterior Cervical Fusion for Fracture Is Not the Same as Fusion for Degenerative Cervical Spine Disease
Authors: Malik Azeem Tariq , Yu Elizabeth , Kim Jeffery , Khan Safdar N. 
Published: October 2022

Study Design/Setting:
Retrospective.

Objective:
To understand differences in 30-day outcomes between patients undergoing posterior cervical fusion (PCF) for fracture versus degenerative cervical spine disease.

Summary of Background Data:
Current bundled payment models for cervical fusions, such as the Bundled Payments for Care Improvement revolve around the use of diagnosis-related groups to categorize patients for reimbursement purposes. Though a PCF performed for a fracture may have a different postoperative course of care as compared with a fusion being done for degenerative cervical spine pathology, the current DRG system does not differentiate payments based on the indication/cause of surgery.

Methods:
The 2012-2017 American College of Surgeons–National Surgical Quality Improvement Program was queried using Current Procedural Terminology code 22600 to identify patients receiving elective PCFs. Multivariate analyses were used to compare rates of 30-day severe adverse events, minor adverse events, readmissions, length of stay, and nonhome discharges between the 2 groups.

Results:
A total 2546 (91.4%) PCFs were performed for degenerative cervical spine pathology and 240 (8.6%) for fracture. After adjustment for differences in baseline clinical characteristics, patients undergoing a PCF for a fracture versus degenerative pathology had higher odds of severe adverse events [18.8% vs. 10.6%, odds ratio (OR): 1.65 (95% CI, 1.10–2.46); P=0.015], prolonged length of stay >3 days [54.2% vs. 40.5%, OR: 1.93 (95% CI, 1.44–2.59); P<0.001], and nonhome discharges [34.2% vs. 27.6%, OR: 1.54 (95% CI, 1.10–2.17); P=0.012].

Conclusions:
Patients undergoing PCFs for fracture have significant higher rates of postoperative adverse events and greater resource utilization as compared with individuals undergoing elective PCF for degenerative spine pathology. The study calls into question the need of risk adjustment of bundled prices based on indication/cause of the surgery to prevent the creation of a financial disincentive when taking care/performing surgery in spinal trauma patients.
Oral Immunotherapy and Risk of Eosinophilic Esophagitis in Children
Authors: Morales‐Cabeza Cristina , Infante Sonsoles , Cabrera‐Freitag Paula , Fuentes‐Aparicio Victoria , Zubeldia José Manuel , Álvarez‐Perea Alberto 
Published: October 2022

Objectives:Oral immunotherapy (OIT) is an effective treatment for children with persistent food allergy, and has concerns about its safety, including eosinophilic esophagitis (EoE). The aim of this study was to evaluate the prevalence of EoE in a large cohort of children who underwent OIT in our center, and to determine if there were any clinical, endoscopic, or histologic differences depending on the food employed for the OIT.Methods:A retrospective study was performed over a 15‐year period (2005–2020). Children who underwent cow’s milk (CM), egg, and/or peanut OIT and developed EoE were included.Results:Six hundred and seven OIT were carried out (277 CM‐OIT, 322 egg‐OIT, and 8 peanut‐OIT). Seventeen patients (2.8%) had a confirmed histologic diagnosis of EoE with a higher prevalence for patients who underwent CM‐OIT (3.9%) than egg‐OIT (2.2%). Symptoms suggestive of EoE and a confirmed diagnosis occurred at median times of 25 and 36 months, respectively, after the build‐up phase of the OIT was completed. Choking, abdominal pain, and dysphagia were the most frequent symptoms and lamina propria fibrosis was observed in 41.2% of patients. No significant differences in clinical symptoms, endoscopic, or histologic findings between patients under CM or egg‐OIT were found. One‐third of patients reported mild symptoms suggestive of EoE before the OIT.Conclusions:EoE appears to be a rare but important adverse event that can occur even years after OIT. Validated questionnaires to screen EoE before the OIT and in the follow‐up of these patients may be the main tool for an early diagnosis.
Impact of Pediatric Dental Resident Availability in the Pediatric Emergency Department
Authors: Fleagle Jenelle , Xiao Wendi , Cottam Michael , Lorch Margarita S. 
Published: October 2022

Objective
The purpose of this study is to describe the impact of Delaware's first pediatric dental residency program on treatment of patients presenting to the pediatric emergency department (PED).

Methods
Charts were reviewed for patients presenting to the PED with a dental chief complaint over a 9-month period with a comparison period. Chief complaint, diagnosis, treatment interventions, disposition, and demographic information were included. χ2, Fisher exact, and Student t tests with a P value less than 0.05 were regarded as significant.

Results
A total of 432 patients met inclusion criteria; 197 before dental residency commencement and 235 after residency commencement. Dental consultation significantly increased (56% vs 7%, P < 0.01) between the study periods. There were no statistically significant differences in sex, race, insurance type, admissions, or proportion of presentations of trauma or infection between the study periods. Dental residents provided in-person evaluation for 40% of patients. The proportion of patients receiving dental intervention increased significantly postresidency period (57% vs 47%, P = 0.04). Pediatric emergency department extractions and splints both occurred in a significantly larger portion of patients after the start of the residency program (17% vs 1% and 5% vs 0%, P < 0.01). A higher proportion of patients with dental complaints received procedural sedation in the PED after residency (13% vs 2%, P < 0.01).

Conclusions
Pediatric dental resident availability in the PED significantly increased dental consultation and intervention. A significantly higher percentage of PED patients received definitive treatment at point of service without requiring referral to another facility.
The Relationship Between Health Literacy and Outcomes Before and After Kidney Transplantation
Authors: Lorenz Elizabeth C. , Petterson Tanya M. , Schinstock Carrie A. , Johnson Bradley K. , Kukla Aleksandra , Kremers Walter K. , Sanchez William , Yost Kathleen J. 
Published: October 2022

Background.
Limited health literacy (HL) is associated with decreased kidney function and death in patients with chronic kidney disease. Less is known about the impact of HL on kidney transplant (KT) outcomes. The aim of this study was to examine the relationship between HL and KT outcomes, including rates of waitlisting, healthcare utilization, acute rejection, renal allograft function, renal allograft failure, and death.

Methods.
We performed a retrospective review of HL data previously collected at our center. HL was assessed in a convenience sample of consecutive, English-speaking patients age ≥18 y who were evaluated for KT at Mayo Clinic in Minnesota between June 2015 and March 2017 as part of a practice improvement feasibility project (n = 690). HL was assessed using the 4-item Brief Health Literacy Screening Tool modified for the outpatient KT evaluation process. The 4 items assess confidence completing forms, reading comprehension, and oral literacy.

Results.
Overall, 30.4% of patients had limited or marginal HL. Patients with limited or marginal HL were less likely than those with adequate HL to be waitlisted for KT (hazard ratio = 0.62 and 0.69, respectively), even after adjusting for age, marital status, body mass index, Charlson comorbidity index, or dialysis dependency. Patient HL was not associated with post-KT healthcare utilization, acute rejection, or renal allograft function. Patients with limited or marginal HL appeared to experience a higher risk of renal allograft failure and post-KT death, but the number of events was small, and the relationship was statistically significant only for marginal HL.

Conclusions.
Inadequate HL is common in KT candidates and independently associated with decreased waitlisting for KT. We observed no statistically significant relationship between HL and posttransplant outcomes in our cohort. Further efforts to improve communication in patients with inadequate HL may improve access to KT.
Noradrenergic input from nucleus of the solitary tract regulates parabrachial activity in mice
Authors: Ji Yadong , Onwukwe Chimdiya , Smith Jesse , Laub Hanna , Posa Luca , Keller Asaf , Masri Radi , Cramer Nathan 
Published: October 2022

AbstractThe parabrachial complex (PB) is critically involved in aversive processes, and chronic pain is associated with amplified activity of PB neurons in rodent models of neuropathic pain. Here we demonstrate that catecholaminergic input from the caudal nucleus of the solitary tract (cNTScat)—a stress responsive region that integrates intero- and exteroceptive signals—causes amplification of PB activity and their sensory afferents. We used a virally mediated expression of a norepinephrine (NE) sensor, NE2h, fiber photometry, and extracellular recordings in anesthetized mice to show that noxious mechanical and thermal stimuli activate cNTS neurons. These stimuli also produce prolonged NE transients in PB that far outlast the noxious stimuli. Similar NE transients can be evoked by focal electrical stimulation of cNTS, a region that contains the noradrenergic A2 cell group that projects densely upon PB. In vitro, optical stimulation of cNTScatterminals depolarized PB neurons and caused a prolonged increase the frequency of excitatory synaptic activity. A dual opsin approach showed that sensory afferents from the caudal spinal trigeminal nucleus are potentiated by cNTScatterminal activation. This potentiation was coupled with a decrease in the paired pulse ratio, consistent with an cNTScat- mediated increase in the probability of release at SpVc synapses. Together, these data suggest that A2 neurons of the cNTS generate long lasting NE transients in PB which increase excitability and potentiate responses of PB neurons to sensory inputs. These reveal a mechanism through which stressors from multiple modalities may potentiate the aversiveness of nociceptive stimuli.Significance StatementIncreased excitability of the parabrachial nucleus (PB), a key integrative hub for aversive stimuli, is linked to amplified pain behaviors. We show that prolonged norepinephrine (NE) transients in PB following noxious stimulation in mice. These NE transients potentiate sensory input to PB and arise, at least in part, from catecholaminergic projections from the caudal nucleus of the solitary tract (cNTScat). We propose that activity this cNTScatto PB pathway may potentiate the aversiveness of pain.
Cortical thickness, gray matter volume and cognitive performance: a cross-sectional study of the moderating effects of age on their inter-relationships
Authors: de Chastelaine Marianne , Srokova Sabina , Hou Mingzhu , Kidwai Amber , Kafafi Seham S. , Racenstein Melanie L , Rugg Michael D 
Published: October 2022

AbstractIn a sample comprising younger, middle-aged and older cognitively healthy adults (N = 375), we examined associations between mean cortical thickness, gray matter volume (GMV) and performance in four cognitive domains - memory, speed, fluency and crystallized intelligence. In almost all cases, the associations were moderated significantly by age, with the strongest associations in the older age group. An exception to this pattern was identified in a younger adult sub-group aged less than 23 yrs, when a negative association between cognitive performance and cortical thickness was identified. Other than for speed, all associations between structural metrics and performance in specific cognitive domains were fully mediated by mean cognitive ability. Cortical thickness and GMV explained unique fractions of the variance in mean cognitive ability, speed and fluency. In no case, however, did the amount of variance jointly explained by the two metrics exceed 7% of the total variance. These findings suggest that cortical thickness and GMV are distinct correlates of domain-general cognitive ability, that the strength and, for cortical thickness, the direction of these associations is moderated by age, and that these structural metrics offer only limited insights into the determinants of individual differences in cognitive performance across the adult lifespan.
Adsorption Race Between Activated Carbon and Lactase for Intermolecular Interaction with Lactose
Authors: Zümrütdal Emin , Kuşvuran Erdal , Kökbaş Umut , Çürük Mine , Mertoğlu Tuba Şimşek , Dağ Büşra , Kılınççeker Güray 
Published: October 2022

AbstractBackgroundDisturbing dyspeptic complaints may be seen in the use of milk and dairy products in people with lactose intolerance. Lactose-free milk and dairy products are produced for people with these complaints. The widespread use of activated carbon for dyspeptic complaints can also be used for adsorbing lactose.MethodsFor this purpose, the binding energy of lactase to lactose was studied in silico, lactose adsorption enthalpic changes of activated carbon were calculated by HPLC, plain and activated carbon yoghurt was produced and glucose+galactose and lactose levels were determined in yoghurts. The effects of these yogurts on serum glucose levels were compared in mice.ResultsIn silico studies, the affinity of lactase with lactose was found to be -7.12 kcal/mol. It was determined by HPLC that activated carbon adsorbed lactose with an energy of -1,785 kcal/mol, and glucose+galactose levels and lactose ratios were lower in yogurt with added activated carbon. It was determined that there was no change in serum glucose levels in the 45th and 90th minutes following fasting in the mice fed with activated carbon yogurt compared to the mice fed plain yogurt.ConclusionYogurt with activated carbon can be an alternative diet for individuals with lactose intolerance, by converting lactose to lactase in the presence of lactase and adsorbing lactose in the absence of lactose.
Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering
Authors: Georgiadis Marios , Menzel Miriam , Reuter Jan A , Born Donald , Kovacevich Sophie , Alvarez Dario , Gao Zirui , Guizar-Sicairos Manuel , Weiss Thomas M , Axer Markus , Rajkovic Ivan , Zeineh Michael M 
Published: October 2022

AbstractMyelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain’s structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons.X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS can serve as a ground truth for validating MRI as well as microscopy-based methods.Statement of SignificanceTo study how the nerve fibers in our brain are interconnected, scientists need to visualize their trajectories, which often cross one another. Here, we show the unique capacity of small-angle X-ray scattering (SAXS) to study these fiber crossings without use of labelling, taking advantage of SAXS’s specificity to myelin - the insulating sheath that is wrapped around nerve fibers. We use SAXS to detect double and triple crossing fibers and unveil intricate crossings in mouse, pig, vervet monkey, and human brains. This non-destructive method can uncover complex fiber trajectories and validate other less specific imaging methods (e.g., MRI or microscopy), towards accurate mapping of neuronal connectivity in the animal and human brain.Graphical Abstract
Integrative CUT&Tag/RNA-Seq analysis of histone variant macroH2A1-dependent orchestration of human iPSCs reprogramming
Authors: Liorni Niccolò , Napoli Alessandro , Castellana Stefano , Giallongo Sebastiano , Řeháková Daniela , Lo Re Oriana , Koutná Irena , Mazza Tommaso , Vinciguerra Manlio 
Published: October 2022

ABSTRACTHuman-induced pluripotent stem cells (iPSCs) can be derived from adult stem cells by forced expression of defined transcription factors. This paves the way for autologous iPSC-derived therapies, which, however, are not yet considered safe. Moreover, reprogramming of somatic cells into iPSCs is an inefficient process, in the range of 0.1%–1%. The epigenetic mechanisms implicated in iPSCs reprogramming are not well understood. The substitution of canonical histone H2A with macroH2A1 histone variant exon-spliced isoforms (macroH2A1.1 and macroH2A1.2) appears as an emerging regulator of iPSCs identity. In particular, we have previously shown that overexpression of macroH2A1.1 led to a more efficient iPSCs reprogramming, by not fully defined mechanisms. Cleavage under targets and tagmentation (CUT&Tag) is a recent methodology used for robust epigenomic profiling of a limited amount of cells. Here, we performed the first integrative CUT&Tag/RNA-Seq analysis of the histone variant macroH2A1-dependent orchestration of iPSCs reprogramming using human umbilical vein endothelial cells (HUVEC) during their reprogramming into iPSC over-expressing tagged macroH2A1.1 or macroH2A1.2. Our results demonstrate a higher and more widespread genome occupancy and a greater number of differentially expressed genes orchestrated by macroH2A1.1 in HUVEC undergoing reprogramming as compared to macroH2A1.2, which involved pervasive functions related to the three embryonic germ layers and increased overlap with CTCF, FOS, GATA2, and POLR2A transcription factor binding sites. In particular, all predicted macroH2A1.1 activating pathways were related to ectoderm/neural processes. As macroH2A1 isoforms have been previously associated with pathologies of the nervous system, our findings may provide relevant molecular insights for modeling neurodegenerative diseases using iPSCs.