bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Institutional Trends in Opioid Prescribing and Utilization after Primary Cleft Lip and Palate Repair”
Authors: Sacks Gina N. , Makar Katelyn G. , Harbaugh Calista M. , Cooper Karen A. , Vercler Christian J. , Kasten Steven J. , Buchman Steven R. , Waljee Jennifer F. 
Published: August 2022

Background:
Outpatient prescriptions for post-operative pain play a significant role in the opioid epidemic. Prescribing guidelines are an effective target for intervention but require procedure-specific data to be successful. The aim of this study was to examine opioid prescribing patterns and pain control after primary cleft lip/palate repair at a large academic center.

Methods:
Children undergoing cleft lip/palate repair from 4/2018-7/2019 were included in a prospective cohort study. Data on discharge prescriptions, refills, and emergency room visits was obtained from the medical record. Caregivers were surveyed 7-21 days after surgery regarding pain control, opioid use, education exposure, storage, and disposal. Chi-square tests and one-way analysis of variance were used to examine predictors of pain control, opioid consumption, safe storage, and disposal.

Results:
After screening, 59 children were included in the study. Patients were 55.8 percent male with a median age of 12 (IQR 5-15) months. Ninety percent of patients received an opioid prescription at discharge with a mean quantity of 10 (IQR 5-15) doses. Ninety-seven percent of caregivers utilized adjunct medication, and opioids were given for a median of 3 [2-6.5] days. Seventy-six percent of caregivers gave less opioid than prescribed. There was no association between pain control and opioid quantity (p=0.68). Twenty-four percent of caregivers used locked storage. Thirty-four percent of respondents with leftover medication reported disposal.

Conclusion:
Opioids are often over-prescribed after cleft lip/palate repair. Providers should consider limiting prescriptions to a 3-day supply to help reduce the quantity of opioids available in the community.
Interfacility Transfer Guidelines for Isolated Facial Trauma: A Multi-disciplinary Expert Consensus.
Authors: Pontell ME , Steinberg JP , Mackay DR , Rodriguez ED , Strong EB , Olsson AB , Kriet JD , Kelly KJ , Ochs MW , Taub PJ , Desai SC , MacLeod S , Susarla S , Tollefson TT , Schubert W , Drolet BC , Golinko MS 
Published: August 2022

Objective.
This study aims to develop guidelines for the transfer of patients with isolated craniomaxillofacial (CMF) trauma.

Methods.
A national, multidisciplinary, expert panel was assembled from leadership in national organizations and contributors to published literature on facial reconstruction. The final panel consisted of five plastic surgeons, four otolaryngologist—head and neck surgeons, and four oral and maxillofacial surgeons. The expert panelist’s opinions on transfer guidelines were collected using the modified Delphi process. Consensus was pre-defined as ≥ 90% agreement per statement.

Results.
After 4 Delphi consensus building rounds, 13 transfer guidelines were established, including statements on fractures of the frontal sinus, orbit, midface and mandible, as well as soft tissue injuries. Twelve guidelines reached consensus.

Conclusions.
The decision to transfer a patient with CMF trauma to another facility is complex and multifactorial. While a percentage of overtriage is acceptable to promote safe disposition of trauma patients, unnecessarily high rates of secondary overtriage divert emergency medical services, increase costs, delay care, overload tertiary trauma centers, and result in tertiary hospital staff providing primary emergency coverage for referring hospitals. These CMF transfer guidelines were designed to serve as a tool to improve, and safely streamline, the care of facial trauma patients. Such efforts may decrease the additional healthcare expenditures associated with secondary overtriage while decompressing emergency medical systems and tertiary emergency departments.
Melanin-Targeted PET Imaging Sheds Light on Pigment Epithelioma in Corpus Ciliare
Authors: Zhang Xiao , Li Mengting , Hu Fan , Lan Xiaoli 
Published: August 2022

Abstract
A 57-year-old woman had gradually decreased visual acuity in the left eye, accompanied by distension and pain. MRI demonstrated a small neoplasm in corpus ciliare, which promoted PET imaging for further assessment. 18F-FDG PET imaging found no obvious uptake in the lesion. However, melanin-targeted PET imaging demonstrated the lesion with avid 18F-PFPN (18F-N-(2-diethylaminoethyl)-4-(2-[2-ethoxy]-ethoxy)pyridine) accumulation (SUVmax, 7.1), which suggested it with melanin expression. Pigmented epithelial adenoma was further confirmed by pathology. Our case illustrated that pigmented epithelial adenoma is characterized by avid 18F-PFPN accumulations and can be detected even in a hidden location with a size of ≤5 mm.
A Single-center Prospective Observational Study Investigating the Accuracy of Preoperative Diagnostic Procedures in the Assessment of Lymph Node Metastases in Nonfunctioning Pancreatic Neuroendocrine Tumors
Authors: Partelli Stefano , Muffatti Francesca , Andreasi Valentina , Giannone Fabio , Rossi Gemma , Palumbo Diego , Mapelli Paola , Schiavo Lena Marco , Arcidiacono Paolo Giorgio , De Cobelli Francesco , Picchio Maria , Doglioni Claudio , Falconi Massimo 
Published: August 2022

Objective:
To determine the accuracy of preoperative imaging, including contrast-enhanced computed tomography (CE-CT), endoscopic ultrasound (EUS), and 68Gallium-DOTATOC positron emission tomography (68Ga-DOTATOC PET), in identifying nodal metastases (N+) in sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs).

Background:
An accurate preoperative identification of N+ in NF-PanNETs is critical for surgical planning. The accuracy of different imaging techniques in detecting lymph node (LN) metastases in NF-PanNETs has been poorly investigated.

Methods:
All consecutive patients undergoing surgery for sporadic NF-PanNETs (2018–2021) were enrolled in a prospective study (DETECTYON; NCT03918759). The accuracy of preoperative imaging techniques in detecting N+ was assessed through sensitivity, specificity positive and negative predictive values.

Results:
Overall, 100 patients with NF-PanNETs underwent CE-CT, EUS, and 68Ga-DOTATOC PET before pancreatic resection. LN metastases were found in 42 cases (42%). Sensitivity, specificity, positive predictive value, and negative predictive value of different imaging techniques were 26%, 95%, 79%, 64% for CE-CT, 19%, 98%, 89%, 63% for EUS, and 12%, 95%, 63%, 60% for 68Ga-DOTATOC PET, respectively. Radiologic tumor size >4 cm and the presence of radiologic N+ at ≥1 imaging were independent predictors of N+ at pathology. The identification of N+ at ≥1 imaging technique was associated with a higher number of positive LNs compared with negative imaging (4 vs 2) (P=0.012).

Conclusions:
CE-CT, EUS, and 68Ga-DOTATOC PET are poorly sensitive in predicting nodal status in NF-PanNETs despite a high specificity.
Ex Vivo Liver Resection and Autotransplantation
Authors: Weiner Joshua , Hemming Alan , Levi David , Beduschi Thiago , Matsumoto Rei , Mathur Abhishek , Liou Peter , Griesemer Adam , Samstein Benjamin , Cherqui Daniel , Emond Jean , Kato Tomoaki 
Published: August 2022

Objective:
We herein advocate for more extensive utilization of ex vivo resection techniques for otherwise unresectable liver tumors by presenting the largest collective American experience.

Background:
Advanced in situ resection and vascular reconstruction techniques have made R0 resection possible for otherwise unresectable liver tumors. Ex vivo liver resection may further expand the limits of resectability but remains underutilized due to concerns about technical complexity and vascular thrombosis. However, we believe that the skillset required for ex vivo liver resection is more widespread and the complications less severe than widely assumed, making ex vivo resection a more attractive option in selected case.

Methods:
We retrospectively analyzed 35 cases performed by surgical teams experienced with ex vivo liver resections (at least 4 cases) between 1997 and 2021.

Results:
We categorized malignancies as highly aggressive (n=18), moderately aggressive (n=14), and low grade (n=3). All patients underwent total hepatectomy, vascular reconstruction and resection in hypothermia on the backtable, and partial liver autotransplantation. Overall survival was 67%/39%/28%, at 1/3/5 years, respectively, with a median survival of 710 days (range: 22–4824). Patient survival for highly aggressive, moderately aggressive, and low-grade tumors was 61%/33%/23%, 67%/40%/22%, and 100%/100%/100% at 1/3/5 years, respectively, with median survival 577 days (range: 22–3873), 444 days (range: 22–4824), and 1825 days (range: 868–3549).

Conclusions:
Ex vivo resection utilizes techniques commonly practiced in partial liver transplantation, and we demonstrate relatively favorable outcomes in our large collective experience. Therefore, we propose that more liberal use of this technique may benefit selected patients in centers experienced with partial liver transplantation.
Virtual oncology research-different models and lessons learned
Authors: Ranganathan P. , Pramesh C.S. 
Published: August 2022

Purpose of review
The COVID-19 pandemic posed several challenges to cancer research including halting of trials, reduced recruitment and protocol violations related to inflexible processes followed in clinical trials. Researchers adopted innovative measures to mitigate these problems and continue studies without compromising their quality. This review collates these adaptations that could well continue after the pandemic.

Recent findings
The COVID-19 pandemic forced researchers globally to adopt innovative measures to overcome the challenges of the pandemic. These included protocol amendments to adjust to the pandemic and travel restrictions, and increased use of digital technologies. ’Virtual’ clinical trials were conducted increasingly with adaptations in ethics and regulatory approvals, patient recruitment and consenting, study interventions and delivery of study medications, trial assessments, and monitoring. Many of these adaptations are safe and feasible, without compromising study quality and data integrity. Although these may not be universally applicable in all types of research, they bring many benefits including more diverse patient participation, less burden on patients for study procedures and reduced resources to conduct trials.

Summary
The COVID-19 pandemic has affected cancer research adversely; however, learnings from the pandemic and adaptations from researchers are likely to improve the efficiency of clinical research beyond the pandemic.
Impact of the COVID-19 pandemic on care and psychological impact on cancer patients
Authors: Mihic-Góngora Luka , Rodriguez-Gonzalez Adán , Velasco Verónica , Obispo Berta , Jiménez-Fonseca Paula , Calderon Caterina 
Published: August 2022

Purpose of review
To summarize the current literature on the psychological impact of COVID-19 on patients with cancer, both in terms of the impact of the virus itself and of changes in the healthcare system; and to describe current recommendations for supporting patients with cancer during the pandemic.

Recent findings
Multiple studies have shown that patients with cancer experience high levels of psychological distress during COVID-19. Factors of greater vulnerability have been described as: being young, being female, low socioeconomic status, lower educational level, having low levels of hope or optimism, lower social support, and having cancer with curative intent. The severe acute respiratory syndrome-coronavirus-2pandemic has accelerated the healthcare digitization process. All departments involved in the diagnosis and treatment of cancer have made contingency plans to minimize the impact on patients.

Summary
Psychological distress is one of the most frequently occurring symptoms in patients with cancer during the pandemic. The COVID-19 pandemic has led to a restructuring of the healthcare system. The paradigm shift may pose a challenge for both healthcare professionals and patients.
Tracking Eye Movements for Diagnosis in Myasthenia Gravis: A Comprehensive Review
Authors: Nguyen Minh N. L. , van der Walt Anneke , Fielding Joanne , Clough Meaghan , White Owen B. 
Published: August 2022

Background:
Around 60%–-75% of myasthenia gravis (MG) patients initially present with nonspecific ocular symptoms. Failed recognition of these symptoms may delay the diagnosis of MG up to 5 years or more, leading to a reduced likelihood of remission and increased morbidity. Current diagnostic tests are either poorly sensitive for patients presenting with ocular symptoms alone or are time consuming, invasive, require a high level of technical expertise, and generally are universally difficult to obtain. This review will explore quantitative eye and pupil tracking as a potential noninvasive, time-effective, and less technically demanding alternative to current diagnostic tests of MG.

Evidence Acquisition:
Comprehensive literature review.

Results:
Thirty-two publications using oculography for the diagnosis of MG and 6 studies using pupillometry were evaluated. In MG patients, extra ocular muscle fatigue was evident in reports of intersaccadic, intrasaccadic and postsaccadic abnormalities, changes in optokinetic nystagmus, slow eye movements, disconjugate saccades, and pupillary constrictor muscle weakness.

Conclusions:
Our review identified several potentially useful variables that derive from oculography and pupillometry studies that could assist with a timely diagnosis of MG. Limitations of this review include heterogeneity in design, sample size, and quality of the studies evaluated. There is a need for larger, well-designed studies evaluating eye-tracking measures in the diagnosis of MG, especially for patients presenting with purely ocular symptoms.
Idiopathic Intracranial Hypertension and Socioeconomic Status in the Greater Toronto Area, Canada
Authors: Eshtiaghi Arshia , Margolin Edward A. , Micieli Jonathan A. 
Published: August 2022

Background:
Previous studies have identified an association between obesity and socioeconomic variables such as poverty, minority status, and a low level of education. Because obesity is a major risk factor for the development of idiopathic intracranial hypertension (IIH), this study aims to identify and assess relationships between socioeconomic and geographic variables in patients with IIH in Canada.

Methods:
A retrospective chart review was performed to identify female patients with IIH presenting to 2 neuro-ophthalmology clinics in Toronto between 2014 and 2022. Consecutive female patients younger than 50 years who did not have IIH were identified as controls. Patient age, body mass index (BMI), and postal code were obtained from electronic medical records. Patient postal codes were then converted to geographic dissemination areas based on the 2016 Canadian census, and data on socioeconomic outcomes were collected from Statistics Canada.

Results:
Three hundred twenty-two female patients with IIH (mean age: 32.3 ± 10) and 400 female controls (mean age: 33.9 ± 9) were included. The mean BMI was 35.0 ± 8 for patients with IIH and 26.7 ± 7 for control patients (P < 0.00001). There was a significant difference between dissemination areas resided by patients with IIH and control patients for median income ($34640 vs $36685 CAD, P = 0.02) and rate of postsecondary degree attainment (57.7% vs 60.5%, P = 0.01). There were no significant differences in the percentage of visible minorities, percentage of immigrants, knowledge of official languages, percentage of married individuals, average household size, or unemployment rate. There was a weak but significant inverse relationship between the rate of postsecondary degree attainment in dissemination areas resided by patients with IIH and their BMI (P = 0.01, R2 = 0.02).

Conclusion:
Patients with IIH reside in geographic areas with lower average levels of income and education than control patients. Patients with lower levels of education may be at higher risk of elevated BMI and therefore disease incidence and progression.
Vision Loss as a Presenting Feature of Chronic Inflammatory Demyelinating Polyneuropathy: A Case Series
Authors: Kruszewski Adam M. , Tauqeer Zujaja , Meer Elana A. , Bautista Sana Ali , Cherayil Neena R. , Cimino Marcus E. , Khella Sami L. , Lancaster Eric , Bird Shawn J. , Scherer Steven S. , Revere Karen E. , Hamedani Ali G. , Liu Grant T. , Tamhankar Madhura A. 
Published: August 2022

Background:
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated, and clinically heterogeneous demyelinating disease affecting the nerve roots and peripheral nerves. We report a series of 4 patients who presented with early and progressive vision loss in the context of new-onset CIDP: 3 due to papilledema and 1 due to optic neuropathy without papilledema.

Methods:
This was a retrospective case series of 4 patients with vision loss as a presenting feature of CIDP evaluated at the Hospital of the University of Pennsylvania from January 2016 to August 2021. Demographic, clinical, diagnostic, and treatment data were collected via retrospective medical record review.

Results:
Case 1 was a 51-year-old man with 2 months of progressive bilateral papilledema associated with reduced visual acuity (count fingers at 1 foot in each eye) and severely constricted visual fields. Case 2 was a 36-year-old man with 4 months of worsening headaches, reduced visual acuity (count fingers at 1 foot in each eye), severely constricted visual fields, and papilledema. Case 3 was a 39-year-old man with papilledema causing progressive vision loss (20/80 in both eyes), headaches, and relapsing limb sensorimotor deficits. Case 4 was a 19-year-old man with 3 months of progressive bilateral visual decline (20/400 in the right eye, 20/600 in the left eye), central scotoma, and optic disc pallor consistent with optic neuropathy without papilledema. All 4 patients met clinical and electrodiagnostic criteria of CIDP. Cases 3 and 4 each tested positive for serum neurofascin-155 IgG4 antibodies. All patients were managed with immunomodulatory therapy. Cases 1 and 2 also each required surgical intervention with bilateral optic nerve sheath fenestration and cerebrospinal fluid (CSF) shunting procedures.

Conclusion:
Vision loss from optic neuropathy with or without papilledema has rarely been reported in CIDP, and typically has been described in the context of longstanding disease. Our cases highlight how CIDP can present with early vision loss that may be profound and challenging to manage if diagnosis is delayed. CIDP should be considered in any patient with new progressive vision loss when associated with peripheral sensorimotor symptoms and elevated CSF protein. The small subgroup of CIDP patients with neurofascin-155 antibodies may be at particular risk of optic nerve involvement.
Establishment of CD8+T cell thymic central tolerance to tissue-restricted antigen requires PD-1
Authors: May Julia F. , Kelly Rees G. , Suen Alexander Y.W. , Rayat Gina R. , Anderson Colin C. , Baldwin Troy A. 
Published: August 2022

AbstractHighly self-reactive T cells are censored from the repertoire by both central and peripheral tolerance mechanisms upon receipt of high-affinity TCR signals. Clonal deletion is considered a major driver of central tolerance; however, other mechanisms such as induction of regulatory T cells and functional impairment have been described. An understanding of the interplay between these different central tolerance mechanisms is still lacking. We previously showed that impaired clonal deletion to a model tissue-restricted antigen (TRA) did not compromise tolerance. In this study, we determined that murine T cells that failed clonal deletion were rendered functionally impaired in the thymus. PD-1 was induced in the thymus and was required to establish cell-intrinsic tolerance to TRA in CD8+thymocytes independently of clonal deletion. PD-1 signaling in developing thymocytes was sufficient for tolerance induction, however in some cases the absence of PD-L1-mediated signaling in the periphery resulted in broken tolerance at late time points. Finally, we showed that chronic exposure to high affinity antigen supported the long-term maintenance of tolerance. Taken together, our study identifies a critical role for PD-1 in establishing central tolerance in autoreactive T cells that escape clonal deletion. It also sheds light on potential mechanisms of action of anti-PD-1 pathway immune checkpoint blockade and the development of immune-related adverse events.Graphical Abstract
High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny
Authors: Lieberman Nicole AP , Armstrong Thaddeus D , Chung Benjamin , Pfalmer Daniel , Hennelly Christopher M , Haynes Austin , Romeis Emily , Wang Qian-Qiu , Zhang Rui-Li , Kou Cai-Xia , Ciccarese Giulia , Conte Ivano Dal , Cusini Marco , Drago Francesco , Nakayama Shu-ichi , Lee Kenichi , Ohnishi Makoto , Konda Kelika A , Vargas Silver K , Eguiluz Maria , Caceres Carlos F , Klausner Jeffrey D , Mitja Oriol , Rompalo Anne , Mulcahy Fiona , Hook Edward W , Hoffmann Irving F , Matoga Mitch M , Zheng Heping , Yang Bin , Lopez-Medina Eduardo , Ramirez Lady G , Radolf Justin D , Hawley Kelly L , Salazar Juan C , Lukehart Sheila A , Seña Arlene C , Parr Jonathan B , Giacani Lorenzo , Greninger Alexander L 
Published: August 2022

AbstractSequencing of most Treponema pallidum (T. pallidum) genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modelling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β- sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.