bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapting SCM for Complex Trauma and Dissociation
Authors: Mitchell Stuart , Anderson Kerry
Published: February 2022

This chapter outlines what structured clinical management-trauma stabilization (SCM-TS) is and how it was developed so that it can be used by generalist practitioners to address complex trauma and dissociation alongside personality disorder problems. SCM-TS is an individual intervention (one session of up to an hour weekly) based on the principles of SCM but adapted to the presenting trauma-related problems brought by the service user. It focuses on three areas: clinical intervention methods and materials, training, and supervision. Some qualitative data is presented on how generalist practitioners have found implementing this adapted form of SCM-TS. Finally, it suggests areas of future research and areas for further clinical development.
Constraints on the Galactic Centre environment from Gaia hyper-velocity stars
Authors: Evans F A , Marchetti T , Rossi E M
Published: February 2022

Following a dynamical encounter with Sgr A*, binaries in the Galactic Centre (GC) can be tidally separated and one member star ejected as a hyper-velocity star (HVS) with a velocity beyond the escape speed of the Milky Way. As GC-born objects located in more observationally accessible regions of the sky, HVSs offer insight into the stellar population in the inner parsecs of the Milky Way. We perform a suite of simulations ejecting stars from the GC, exploring how detectable HVS populations depend on assumptions concerning the GC stellar population, focusing on HVSs that would appear in current and/or future data releases from the Gaia space mission with precise astrometry and measured radial velocities. We show that predictions are sensitive to two parameters in particular: the shape of the stellar initial mass function (IMF) in the GC and the ejection rate of HVSs. The absence of confident HVS candidates in Gaia Data Release 2 excludes scenarios in which the HVS ejection rate is $\gtrsim 3\times 10^{-2} \, \mathrm{yr^{-1}}$. Stricter constraints will be placed on these parameters when more HVS candidates are unearthed in future Gaia data releases – assuming recent determinations of the GC IMF shape, one confident HVS at minimum is expected in Gaia DR3 and DR4 as long as the HVS ejection rate is greater than $\sim 10^{-3}$ and $\sim 10^{-5} \, \mathrm{yr^{-1}}$, respectively.
EDGE: What shapes the relationship between H i and stellar observables in faint dwarf galaxies?
Authors: Rey Martin P , Pontzen Andrew , Agertz Oscar , Orkney Matthew D A , Read Justin I , Saintonge Amélie , Kim Stacy Y , Das Payel
Published: February 2022

We show how the interplay between feedback and mass-growth histories introduces scatter in the relationship between stellar and neutral gas properties of field faint dwarf galaxies ($M_{\star }\lessapprox 10^{6} \, \mbox{M}_\mathrm{\odot }$). Across a suite of cosmological, high-resolution zoomed simulations, we find that dwarf galaxies of stellar masses $10^5 \le M_{\star }\le 10^{6} \, \mbox{M}_\mathrm{\odot }$ are bimodal in their cold gas content, being either H i-rich or H i-deficient. This bimodality is generated through the coupling between (i) the modulation of H i contents by the background of ultraviolet radiation (UVB) at late times and (ii) the significant scatter in the stellar-to-halo mass relationship induced by reionization. Furthermore, our H i-rich dwarfs exhibit disturbed and time-variable neutral gas distributions primarily due to stellar feedback. Over the last four billion years, we observe order-of-magnitude changes around the median $M_{\mathrm{H\,\small {I} }}$, factor-of-a-few variations in H i spatial extents, and spatial offsets between H i and stellar components regularly exceeding the galaxies’ optical sizes. Time variability introduces further scatter in the $M_{\star }\!-\! M_{\mathrm{H\,\small {I} }}$ relation and affects a galaxy’s detectability in H i at any given time. These effects will need to be accounted for when interpreting observations of the population of faint, H i-bearing dwarfs by the combination of optical and radio wide, deep surveys.
Observations of PAHs in the atmospheres of discs and exoplanets
Authors: Ercolano Barbara , Rab Christian , Molaverdikhani Karan , Edwards Billy , Preibisch Thomas , Testi Leonardo , Kamp Inga , Thi Wing-Fai
Published: February 2022

Polycyclic aromatic hydrocarbons (PAHs) play a key role in the chemical and hydrodynamical evolution of the atmospheres of exoplanets and planet-forming discs. If they can survive the planet formation process, PAHs are likely to be involved in pre-biotic chemical reactions eventually leading to more complex molecules such as amino acids and nucleotides, which form the basis for life as we know it. However, the abundance and specific role of PAHs in these environments is largely unknown due to limitations in sensitivity and range of wavelength of current and previous space-borne facilities. Upcoming infrared space spectroscopy missions, such as Twinkle and Ariel, present a unique opportunity to detect PAHs in the atmospheres of exoplanets and planet-forming discs. In this work, we present synthetic observations based on conservative numerical modelling of typical planet-forming discs and a transiting hot Saturnian planet around solar-type star. Our models show that Twinkle and Ariel might both be able to detect the 3.3 $\mu$m PAH feature within reasonable observing time in discs and transiting planets, assuming that PAHs are present with an abundance of at least one-tenth of the interstellar medium value.
Standardizing Platinum Dainotti-correlated gamma-ray bursts, and using them with standardized Amati-correlated gamma-ray bursts to constrain cosmological model parameters
Authors: Cao Shulei , Dainotti Maria , Ratra Bharat
Published: February 2022

We show that the Platinum gamma-ray burst (GRB) data compilation, probing the redshift range 0.553 ≤ z ≤ 5.0, obeys a cosmological-model-independent three-parameter Fundamental Plane (Dainotti) correlation and so is standardizable. While they probe the largely unexplored z ∼ 2.3–5 part of cosmological redshift space, the GRB cosmological parameter constraints are consistent with, but less precise than, those from a combination of baryon acoustic oscillation (BAO) and Hubble parameter [H(z)] data. In order to increase the precision of GRB-only cosmological constraints, we exclude common GRBs from the larger Amati-correlated A118 data set composed of 118 GRBs and jointly analyse the remaining 101 Amati-correlated GRBs with the 50 Platinum GRBs. This joint 151 GRB data set probes the largely unexplored z ∼ 2.3–8.2 region; the resulting GRB-only cosmological constraints are more restrictive, and consistent with, but less precise than, those from H(z)  + BAO data.
EWS splicing regulation contributes to balancingFoxp1isoforms required for neuronal differentiation
Authors: Verdile Veronica , Svetoni Francesca , La Rosa Piergiorgio , Ferrante Gabriele , Cesari Eleonora , Sette Claudio , Paronetto Maria Paola
Published: February 2022

Alternative splicing is a key regulatory process underlying the amplification of genomic information and the expansion of proteomic diversity, particularly in brain. Here, we identify the Ewing sarcoma protein (EWS) as a new player of alternative splicing regulation during neuronal differentiation. Knockdown of EWS in neuronal progenitor cells leads to premature differentiation. Transcriptome profiling of EWS-depleted cells revealed global changes in splicing regulation. Bioinformatic analyses and biochemical experiments demonstrated that EWS regulates alternative exons in a position-dependent fashion. Notably, several EWS-regulated splicing events are physiologically modulated during neuronal differentiation and EWS depletion in neuronal precursors anticipates the splicing-pattern of mature neurons. Among other targets, we found that EWS controls the alternative splicing of the forkhead family transcription factor FOXP1, a pivotal transcriptional regulator of neuronal differentiation, possibly contributing to the switch of gene expression underlying the neuronal differentiation program.
Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors
Authors: Herrgott Grayson A , Asmaro Karam P , Wells Michael , Sabedot Thais S , Malta Tathiane M , Mosella Maritza S , Nelson Kevin , Scarpace Lisa , Barnholtz-Sloan Jill S , Sloan Andrew E , Selman Warren R , deCarvalho Ana C , Poisson Laila M , Mukherjee Abir , Robin Adam M , Lee Ian Y , Snyder James , Walbert Tobias , Rosenblum Mark , Mikkelsen Tom , Bhan Arti , Craig John , Kalkanis Steven , Rock Jack , Noushmehr Houtan , Castro Ana Valeria
Published: February 2022

Background

DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases.

Methods

We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET.

Results

Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets.

Conclusions

Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.
Artificial Intelligence-based Radiomics in the Era of Immuno-oncology
Authors: Kang Cyra Y , Duarte Samantha E , Kim Hye Sung , Kim Eugene , Park Jonghanne , Lee Alice Daeun , Kim Yeseul , Kim Leeseul , Cho Sukjoo , Oh Yoojin , Gim Gahyun , Park Inae , Lee Dongyup , Abazeed Mohamed , Velichko Yury S , Chae Young Kwang
Published: February 2022

The recent, rapid advances in immuno-oncology have revolutionized cancer treatment and spurred further research into tumor biology. Yet, cancer patients respond variably to immunotherapy despite mounting evidence to support its efficacy. Current methods for predicting immunotherapy response are unreliable, as these tests cannot fully account for tumor heterogeneity and microenvironment. An improved method for predicting response to immunotherapy is needed. Recent studies have proposed radiomics—the process of converting medical images into quantitative data (features) that can be processed using machine learning algorithms to identify complex patterns and trends—for predicting response to immunotherapy. Because patients undergo numerous imaging procedures throughout the course of the disease, there exists a wealth of radiological imaging data available for training radiomics models. And because radiomic features reflect cancer biology, such as tumor heterogeneity and microenvironment, these models have enormous potential to predict immunotherapy response more accurately than current methods. Models trained on preexisting biomarkers and/or clinical outcomes have demonstrated potential to improve patient stratification and treatment outcomes. In this review, we discuss current applications of radiomics in oncology, followed by a discussion on recent studies that use radiomics to predict immunotherapy response and toxicity.
FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Follicular Lymphoma
Authors: Bouchkouj Najat , Zimmerman Megan , Kasamon Yvette L , Wang Cong , Dai Tianjiao , Xu Zhenzhen , Wang Xiaofei , Theoret Marc , Purohit-Sheth Tejashri , George Bindu
Published: February 2022

In March 2021, the U.S. Food and Drug Administration granted accelerated approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor T-cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma (r/r FL) after at least 2 lines of systemic therapy. Approval was based on ZUMA-5, a single-arm, open-label, multicenter trial that evaluated a single infusion of axicabtagene ciloleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine, in this population. Efficacy was based on objective response rate (ORR) and duration of response (DOR) as determined by an independent review committee. Among 81 patients in the primary efficacy analysis, having a median of 3 (range 2-9) prior lines of systemic therapy, the ORR was 91% (95% confidence interval [CI]: 83-96) with a complete remission (CR) rate of 60% and a median time-to-response of 1 month. The median DOR was not reached, and the 1-year rate of continued remission was 76% (95% CI: 64-85). For all leukapheresed patients with FL in this trial (n = 123), the ORR was 89% (95% CI: 83-94) with a CR rate of 62%. Among 146 patients with indolent lymphoma evaluated for safety, cytokine release syndrome occurred in 84% (Grade ≥3, 8%) and neurological toxicities occurred in 77% (Grade ≥3, 21%), leading to implementation of a risk evaluation and mitigation strategy. Serious adverse reactions occurred in 48%. Post-marketing studies will further evaluate clinical benefit in patients with r/r FL and long-term safety.
MicroRNA828 negatively regulates lignin biosynthesis in stem of Populus tomentosa through MYB targets
Authors: Wang Xianqiang , Yao Shu , Htet Win Pa Pa Myo , Yue Yuchen , Zhang Zhuanzhuan , Sun Kuan , Chen Sijie , Luo Keming , Fan Di
Published: February 2022

Lignin biosynthesis in the sclerenchyma cells is strictly controlled by a complex network of genetic and environmental signals. In the last decades, the transcriptional regulation of lignin synthesis in woody species has been established. However, the role of microRNA-mediated post-transcriptional modulation in secondary cell wall biosynthesis remains poorly understood. Here, we identified a microRNA, miR828, involved in the regulation specific to lignin biosynthesis during stem development in Populus tomentosa Carr. miR828 is preferentially expressed in the secondary vascular tissues during stem development. Two MYB genes (MYB171 and MYB011) were validated as direct targets of miR828 by degradome analysis and green fluorescent protein signal detection. Overexpression of miR828 in poplar downregulated genes for lignin biosynthesis, resulting in reduced lignin content in cell walls. Conversely, suppression of miR828 in plants by the short tandem target mimics elevated the expression of lignin biosynthetic genes and increased lignin deposition. We further revealed that poplar MYB171, as the most abundant miR828 target in the stem, is a positive regulator for lignin biosynthesis. Transient expression assays showed that both MYB171 and MYB011 activated PAL1 and CCR2 transcription, whereas the introduction of miR828 significantly suppressed their expression that was induced by MYB171 or MYB011. Collectively, our results demonstrate that the miR828-MYBs module precisely regulates lignin biosynthesis during the stem development in P. tomentosa through transcriptional and post-transcriptional manners.
Characteristics of Nursing Home Resident Movement Patterns: Results from the TEAM-UP Trial
Authors: Kennerly Susan M. , Sharkey Phoebe D. , Horn Susan D. , Zheng Tianyu , Alderden Jenny , Sabol Valerie K. , Rowe Meredeth , Yap Tracey L.
Published: February 2022

OBJECTIVE

To determine movement patterns of nursing home residents, specifically those with dementia or obesity, to improve repositioning approaches to pressure injury (PrI) prevention.

METHODS

A descriptive exploratory study was conducted using secondary data from the Turn Everyone And Move for Ulcer Prevention (TEAM-UP) clinical trial examining PrI prevention repositioning intervals. K-means cluster analysis used the average of each resident’s multiple days’ observations of four summary mean daily variables to create homogeneous movement pattern clusters. Growth mixture models examined movement pattern changes over time. Logistic regression analyses predicted resident and nursing home cluster group membership.

RESULTS

Three optimal clusters partitioned 913 residents into mutually exclusive groups with significantly different upright and lying patterns. The models indicated stable movement pattern trajectories across the 28-day intervention period. Cluster profiles were not differentiated by residents with dementia (n = 450) or obesity (n = 285) diagnosis; significant cluster differences were associated with age and Braden Scale total scores or risk categories. Within clusters 2 and 3, residents with dementia were older (P < .0001) and, in cluster 2, were also at greater PrI risk (P < .0001) compared with residents with obesity; neither group differed in cluster 1.

CONCLUSIONS

Study results determined three movement pattern clusters and advanced understanding of the effects of dementia and obesity on movement with the potential to improve repositioning protocols for more effective PrI prevention. Lying and upright position frequencies and durations provide foundational knowledge to support tailoring of PrI prevention interventions despite few significant differences in repositioning patterns for residents with dementia or obesity.
Reconsidering the Trendelenburg position during intradialytic hypotension
Authors: Geer Kristine D.
Published: February 2022

Intradialytic hypotension (IDH) is the most common complication that patients experience during hemodialysis. This article discusses IDH and its emergency management, focusing on Trendelenburg position, which may create more risks than benefits.
Persistent Postgastrectomy Hypoglycemia Unawareness in Patients With Gastric Cancer Unveiled by a Prospective Study
Authors: Kubota Takeshi , Yubakami Masayuki , Ushigome Emi , Ohashi Takuma , Shoda Katsutoshi , Konishi Hirotaka , Shiozaki Atsushi , Fujiwara Hitoshi , Okamoto Kazuma , Fukui Michiaki , Otsuji Eigo
Published: February 2022

Objective:

Late dumping syndrome is a common postgastrectomy complication characterized by reactive hypoglycemia. This study aimed to explore the glycemic trend in patients who underwent gastrectomy for gastric cancer and clarify its changes over time in association with postgastrectomy symptoms.

Summary Background Data:

Changes over time in glycemic trend in association with postgastrectomy symptoms have not been evaluated.

Methods:

We conducted a prospective study of 71 patients who underwent curative gastrectomy for gastric cancer between November 2017 and April 2020. The patients underwent continuous glucose monitoring twice—at 1- and 12-month postgastrectomy—and were assessed using the Post-Gastrectomy Syndrome Assessment Scale 37-item questionnaire (PGSAS-37) at 1-, 6-, and 12-month postgastrectomy.

Results:

Our results revealed that hypoglycemia (<70 mg/dL), especially nocturnal hypoglycemia (00:00−06:00), frequently occurred even at 12-month postgastrectomy. Hypoglycemia improved in total gastrectomy patients but remained unchanged in distal gastrectomy patients, which was still high in both groups at 12-month postgastrectomy. Glycemic variability (SD of the glycemic trend) was exacerbated in both gastrectomy groups. However, the PGSAS-37 symptom scores remained unchanged, and the living status and quality of life tended to improve. Hypoglycemia unawareness, including postprandial hypoglycemia without symptoms and nocturnal hypoglycemia, was evident even 12-month postgastrectomy.

Conclusions:

Persistent postgastrectomy hypoglycemia unawareness, including late dumping syndrome without symptoms and nocturnal hypoglycemia, should be recognized as an important issue in postgastrectomy syndrome. Therefore, meticulous long-term evaluation for glycemic trends and care of patients is required.
Upregulation of transient receptor potential cation channel subfamily M member-3 in bladder afferents is involved in chronic pain in cyclophosphamide-induced cystitis
Authors: Zhao Mengmeng , Liu Lei , Chen Zhenghao , Ding Ning , Wen Jiliang , Liu Jiaxin , Ge Nan , Zhang Xiulin
Published: February 2022

The transient receptor potential cation channel subfamily M member-3 (TRPM3) channel is a recently recognized noxious heat sensor that is involved in inflammatory thermal hyperalgesia. To examine its involvement in the development of hyperalgesia in interstitial cystitis/painful bladder syndrome (IC/PBS), rats with cyclophosphamide (CYP)-induced chronic cystitis were used as a model of IC/PBS. Mechanical and thermal hyperalgesia in lower abdominal region overlying the bladder in CYP rats were measured using von Frey filaments and radiant heat, respectively. Transient receptor potential cation channel subfamily M member-3 expression at the mRNA, protein, and functional levels in dorsal root ganglion neurons innervating the bladder was detected using RNA in situ hybridization (RNAscope), Western blotting, immunohistochemistry, and Ca2+ imaging, respectively. Transient receptor potential cation channel subfamily M member-3 channels were expressed on most of the bladder primary afferent nerve terminals containing calcitonin gene–related peptide and their cell bodies in L6-S1 dorsal root ganglion. Activation of TRPM3 in the bladder wall by its specific agonist pregnenolone sulphate or CIM0216 induced spontaneous bladder pain, calcitonin gene–related peptide release, and neurogenic inflammation that was evidenced by edema, plasma extravasation, inflammatory cell accumulation, and mast cell infiltration. In CYP rats, pretreatment with the TRPM3 antagonist primidone (2 mg/kg, i.p.) significantly alleviated the mechanical and thermal hyperalgesia, bladder submucosal edema, mast cell infiltration, and bladder hyperactivity. Cyclophosphamide-induced cystitis was associated with TRPM3 upregulation at the mRNA, protein, and functional levels in bladder afferent neurons. Our results suggest that upregulation of TRPM3 channels is involved in the development of chronic pain in CYP-induced cystitis, and targeting TRPM3 may be a pharmacological strategy for treating bladder pain in IC/PBS.
Preoperative Imaging of Temporoparietal Scalp Thickness Predicts Off-the-Ear Sound Processor Retention in Cochlear Implants With Diametric Magnets
Authors: Adkins Weston J. , Henrie Tanner , Nassiri Ashley M. , Neff Brian A. , Carlson Matthew L. , Driscoll Colin L. W. , Saoji Aniket A.
Published: February 2022

Objective:

To determine if temporoparietal scalp thickness assessed via preoperative imaging predicts retention events in patients who have cochlear implants with diametric magnets and various sound processor types.

Study Design:

Retrospective chart and radiological review.

Setting:

Tertiary referral center.

Patients:

One hundred forty-three adult patients who have cochlear implants with diametric magnets.

Main Outcome Measures:

Skin flap thickness, retention events, body mass index (BMI), and magnet strength.

Results:

Of 42 patients with the most recent generation off-the-ear sound processor (OTE2), 13 (31.0%) had retention events. Of patients with a temporoparietal scalp thickness less than 8 mm, all patients could ultimately retain the device, though one of 26 was noted to have tenuous retention. Of patients with 8 to 10 mm skin flaps, 3 of 6 (50%) could not retain the device, and with more than 10 mm skin flaps, 7 of 10 (70%) could not retain the device. In the more than 10 mm group, two additional patients could not either retain the device at initial activation or were noted to have tenuous retention. Of 124 patients with behind-the-ear (BTE) sound processors, only 2 (1.6%) could not retain the device at initial activation, and 3 (2.4%) exhibited tenuous retention after 3 months of device use. Results from the first generation off-the-ear sound processor (OTE1) are also reported.

Conclusions:

Temporoparietal scalp thickness measured by preoperative imaging is associated with processor retention for patients with the OTE2 sound processor and diametric magnets. All patients with less than 8 mm scalp thickness could retain the OTE2, while 50% of patients with 8 to 10 mm scalp thickness and 70% with more than 10 mm scalp thickness could not retain the device. Patients should be counseled regarding their sound processor choice and/or considered candidates for skin flap reduction or other intervention as indicated. Retention events with BTE processors are rare.
Multidisciplinary Care for Adults With Chronic Pancreatitis
Authors: Petrik Megan L. , Freeman Martin L. , Trikudanathan Guru
Published: February 2022

Chronic pancreatitis (CP) is associated with a high disease burden, extensive negative impact on quality of life, increased rates of depression and anxiety, and significant health care utilization and expenditures. Pain is a hallmark feature of CP, present in up to 90% of patients with this condition, and can lead to high rates of disability, hospitalization, and opioid medication use. Current perspectives on the management of CP have evolved to advocate a multidisciplinary approach which offers new pathways for helping patients manage symptoms. Psychologists play an important role in a multidisciplinary team effort by applying scientifically based psychological principles and techniques to improve pain and adaptation to chronic illness. This review will detail the fundamentals of delivering psychological interventions for adults with CP managed in an outpatient setting. Recommendations for integrating psychological care in multidisciplinary management of CP will be offered. Future directions for psychological care in CP multidisciplinary teams are also discussed.
Identification of Malnutrition Risk Using Malnutrition Screening Tool in an Ambulatory Pancreas Clinic
Authors: Madril Peter , Golian Paige , Nahikian-Nelms Marcia , Hinton Alice , Hart Philip A. , Roberts Kristen M.
Published: February 2022

Objectives

The aim of this project was to assess malnutrition risk in a well-defined cohort of pancreatic diseases.

Methods

We performed a retrospective, cross-sectional study of 401 subjects with available malnutrition screening tool scores who received care at a single outpatient pancreas clinic during a 6-month study period. Univariate analyses were performed to compare demographic, anthropometric, symptoms/diseases, and risk for malnutrition characteristics across 3 strata of diseases: acute pancreatitis (n = 141), chronic pancreatitis (n = 193), and other pancreatic diagnoses (n = 67).

Results

A total of 18% of subjects were identified as at risk for malnutrition, including 25% who reported involuntary weight loss and/or decreased appetite. Subjects categorized as at risk for malnutrition were more likely to have gastrointestinal symptoms. Although the nutrition consultation rates were higher in subjects at risk for malnutrition (P = 0.03), 66% did not receive a clearly indicated dietary evaluation or management recommendations. One fifth of all patients in an ambulatory pancreas clinic are identified as at risk for malnutrition using a simple, validated tool.

Conclusions

The majority of patients at increased risk for nutritional complications did not receive nutritional recommendations.
Toll-Like Receptor 3 Is Critical to the Pancreatic Islet Milieu That Is Required for Coxsackievirus B4–Induced Type 1 Diabetes in Female Nonobese Diabetic Mice
Authors: Benner Sarah E. , Walter Debra L. , Thuma Jean R. , Courreges Maria , James Calvin B. L. , Schwartz Frank L. , McCall Kelly D.
Published: February 2022

Objective

Genetic and environmental influences play a role as triggers of type 1 diabetes mellitus (T1DM). Female nonobese diabetic (NOD) mice are useful for studying T1DM as they spontaneously develop T1DM, which can be accelerated by some viruses. Toll-like receptor 3 (TLR3) is believed to play a critical role in viral-induced T1DM and β-cell destruction, because female Tlr3 knockout (Tlr3
−/−) NOD mice are protected from Coxsackievirus B4 (CVB4)-induced acceleration of T1DM. However, the exact role(s) TLR3 plays in the pathogenesis of CVB4-induced T1DM remain unknown.

Methods

This longitudinal study used immunostaining, laser capture microdissection, and reverse transcription real-time polymerase chain reaction of islets from female uninfected and CVB4-infected Tlr3
+/+ and Tlr3
−/− NOD mice.

Results

Islets isolated from female Tlr3+/+
NOD mice 4 to 8 weeks of age had higher amounts of insulitis, Cxcl10, Il1b, Tnfa, and Tgfb1 expression compared with Tlr3−/−
NOD mice. After CVB4 infection, Tlr3+/+
NOD mice had higher amounts of insulitis and T-cell infiltration at 3 days after infection compared with Tlr3−/−
CVB4-infected NOD mice.

Conclusions

Toll-like receptor 3 is necessary for establishment of a pancreatic islet inflammatory microenvironment by increasing insulitis and cytokine expression that facilitates CVB4-induced T1DM in female NOD mice.
Ptf1a Promoter-Driven Cre Expression During Spermatogenesis Causes Germline Recombination
Authors: Wang Jiale , Wang Oliver , Bi Yan , Wang Ying , Crawford Howard , Ji Baoan
Published: February 2022

Objectives

Two independently developed Ptf1a-Cre mouse lines, Ptf1atm1(cre)Hnak and Ptf1atm1(Cre)Cvw, are widely used in pancreatic research. Recently, Ptf1atm1(cre)Hnak line was reported to transmit unwanted paternal recombination. We aimed to investigate whether this exists in the Ptf1atm1(Cre)Cvw line.

Methods

Ptf1atm1(Cre)Cvw mice were crossed with R26-LSL-LacZ reporter mice. DNA recombination and gene expression were examined by recombination-specific polymerase chain reaction, reverse transcription–polymerase chain reaction, and X-Gal staining.

Results

R26 locus recombination was detected in the pancreas as well as the testes and sperm of the double transgenic mice. Positive ptf1a mRNA expression from testes revealed that there was endogenous Ptf1a promoter activity in this extrapancreatic tissue. Of the 15 progenies that inherited LacZ from the male double transgenic mice, 4 (26.7%) were positive for complete whole-body recombination. The presence of recombination in R26 only mice suggested that the recombination occurred before meiosis.

Conclusions

Paternal germline recombination exists in the Ptf1atm1(Cre)Cvw mouse line. Ptf1a promoter-driven Cre expression during spermatogenesis before meiosis is the cause of germline recombination. Therefore, when male Ptf1a-Cre mice are used in compound mice breeding, it is necessary to genotype not only floxed alleles but also recombined alleles to examine unwanted recombinations.
Chronic Jetlag Alters the Landscape of the Pancreatic Lipidome
Authors: Schwartz Patrick B. , Barrett-Wilt Gregory A. , Ronnekleiv-Kelly Sean M.
Published: February 2022

Objectives

The innate biologic clock plays a significant role in lipid metabolism, including the peripheral clock in the pancreas. However, an evaluation of the downstream lipids in the pancreatic lipidome is lacking. We sought to understand the diurnal variations of lipids within the pancreatic lipidome.

Methods

At 4 weeks of age, C57Bl/6J mice were subjected to either normal lighting conditions or a chronic jetlag (CJ) condition known to mimic chronic shiftwork in humans. At 9 months, mice were serially killed at 4-hour intervals for 24 hours. The pancreas was removed and subjected to untargeted liquid chromatography–mass spectrometry to examine the pancreatic lipidome.

Results

A total of 4.7% of the pancreatic lipidome was rhythmically expressed, which increased to 12.9% after CJ. After CJ, there was a 4.58-hour shift in the timing of peak 24-hour lipid expression. Chronic jetlag also led to the enrichment of diacylglycerols and triglycerides, while promoting a decrease in lysophosphatidylcholines and 44-carbon acyl chain lipids.

Conclusions

The pancreatic lipidome exhibits diurnal rhythmicity across a broad number of lipid classes. Chronic jetlag led to alterations in lipid composition that mirrored other metabolically active organs. Several of the reported changes may link altered sleep-wake cycles with known circadian disruption-induced pancreatic diseases.
Differentiation Between Solid Pseudopapillary Neoplasm of the Pancreas and Nonfunctional Pancreatic Neuroendocrine Neoplasm Using Endoscopic Ultrasound
Authors: Kataoka Kunio , Ishikawa Takuya , Ohno Eizaburo , Mizutani Yasuyuki , Iida Tadashi , Furukawa Kazuhiro , Nakamura Masanao , Honda Takashi , Ishigami Masatoshi , Kawashima Hiroki , Hirooka Yoshiki , Fujishiro Mitsuhiro
Published: February 2022

Objectives

We investigated the utility of endoscopic ultrasound (EUS) for differentiating between solid pseudopapillary neoplasm of the pancreas (SPN) and pancreatic neuroendocrine neoplasm (PanNEN).

Methods

A retrospective analysis was performed on 29 and 77 consecutive patients with pathologically proven SPN and nonfunctional PanNEN. In patients who underwent contrast-enhanced harmonic EUS (CH-EUS), lesions were classified into 3 vascular patterns (hypoechoic/isoechoic/hyperechoic), and the presence of “the alveolus nest sign,” which we previously reported as a characteristic feature of SPN on CH-EUS, was also assessed.

Results

Conventional EUS findings showed that calcification echoes were significantly more frequent in SPN lesions than in PanNEN lesions (19/29 [66%] vs 21/77 [27%], P = 0.001) as was internal isoechogenicity or hyperechogenicity (10/29 [34%] vs 11/77 [14%], P = 0.029). Contrast-enhanced harmonic EUS findings showed that SPN lesions more frequently had the isoechoic or hypoechoic vascular pattern, and significantly more frequently had the alveolus nest sign (18/25 [72%] vs 4/60 [7%], P < 0.001). In a multivariate analysis, the presence of the alveolus nest sign contributed the most to the SPN diagnosis (odds ratio, 70; 95% confidence interval, 6.2–786).

Conclusions

Endoscopic ultrasound, particularly the presence of the alveolus nest sign on CH-EUS, is useful for differentiating SPN from PanNEN.
Provider Differences in Monitoring and Management of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis
Authors: Srivoleti Padmavathi , Dolan Russell D. , Yang Allison L. , Jin David X. , Banks Peter A. , McNabb-Baltar Julia
Published: February 2022

Objectives

Chronic pancreatitis (CP) is a common cause of exocrine pancreatic insufficiency (EPI). Regular monitoring and treatment are recommended to decrease morbidity. This study evaluates whether provider type impacts EPI monitoring and management in CP.

Methods

Fecal elastase 1 (FE-1) testing and pancreatic enzyme replacement therapy (PERT) utilization were retrospectively compared between primary care providers (PCPs), gastroenterologists and pancreas specialists using pairwise comparisons. Multivariate analysis was conducted to study the association between adequate PERT and age, sex, race, insurance status, provider type, and etiology.

Results

Among 256 patients, FE-1 was measured in 115 (44.9%) and of 143 (55.9%) patients who received PERT, 100 (69.9%) received adequate dosage. Fecal elastase 1 testing was performed in 7/57 (12.3%) by PCP, 11/38 (28.9%) by gastroenterologists, and 97/161 (60.2%) by pancreas specialists (P < 0.0001). Adequate PERT was prescribed in 7/24 (29.2%) patients by PCPs, 11/20 (55.0%) by gastroenterologists, and 82/99 (82.8%) by pancreas specialists (P < 0.0001). On multivariate analysis, pancreas specialists were significantly more likely to prescribe adequate PERT compared with PCP (odds ratio, 11.3; 95% confidence interval, 3.3–38.2; P < 0.001).

Conclusions

Many patients with CP receive inadequate surveillance and EPI treatment. Pancreas specialists are more likely to surveil and treat EPI adequately.
The Caring for Our Own Program
Authors: Larsson Laura , Johnson Catherine M.
Published: February 2022

Background:

Research has identified workforce diversification as influential in improving health outcomes. The Caring for Our Own Program (CO-OP) set out to achieve classroom and workforce parity for rural Native American nurses and communities.

Purpose:

In this study, we report quantitative results of the first 20 years of the CO-OP and explore the extent to which the CO-OP model influenced degree completion for Native American students.

Approach:

The CO-OP employs a 4-pillar program model where sense of place, financial security, academic readiness, and social connection empower students as they progress. One hundred twenty-one Native American students have earned nursing degrees since inception. In addition, more than 10% of CO-OP undergraduates have returned to become nurse practitioners.

Conclusions:

The CO-OP model replicated elsewhere may also succeed by adapting key concepts in that context to achieve health equity.
High-Risk Human Papillomavirus Messenger RNA Testing Using Urine, Cervicovaginal Self-Collected and Provider-Collected Cervical Samples Among Women in Mombasa, Kenya
Authors: Grabert Brigid K. , Islam Jessica Y. , Mutua Michael , Kabare Emmanuel , Manguro Griffins , Waweru Wairimu , Mandaliya Kishor , Shafi Juma , McClelland R. Scott , Smith Jennifer S.
Published: February 2022

We compared human papillomavirus messenger RNA testing using urine, self-, and provider-collected samples for the detection of high-grade cervical cytology and assessed acceptability of urine self-collection among females who engage in sex work in Kenya. Participants found urine sampling comfortable, but high-risk human papillomavirus messenger RNA detection in urine samples was less likely to detect high-grade lesions than self- and provider-collected cervical samples.
Misleading Morphologic and Phenotypic Features (Transdifferentiation) in Solitary Fibrous Tumor of the Head and Neck
Authors: Baněčková Martina , Michal Michael , Hájkova Veronika , Haller Florian , Mosaieby Elaheh , Salajka Pavel , Arolt Christoph , Nachtsheim Lisa , Michal Michal , Agaimy Abbas , Skálová Alena
Published: February 2022

Solitary fibrous tumor (SFT) is a rare fibroblastic neoplasm with potentially malignant behavior that may develop in any anatomic site and may involve the head and neck (H&N) region as well. Although typical SFT has a relatively characteristic morphology, its morphologic spectrum is extraordinarily broad and also includes rare cases with dedifferentiation or transdifferentiation which result in aberrant morphologic and/or immunohistochemical features. However, since virtually all cases are molecularly characterized by NAB2::STAT6 gene fusions, molecular genetic methods or STAT6 immunohistochemistry can be effectively used in confirming the diagnosis. Herein, we report 3 diagnostically challenging H&N SFT cases with an unusual morphology and/or phenotypes closely mimicking other well-known H&N entities. The tumors originated in the oral minor salivary glands, the base of the tongue, and sinonasal tract and closely resembled hyalinizing clear cell carcinoma of the salivary gland, adenocarcinoma not otherwise specified and biphenotypic sinonasal sarcoma, respectively. All cases were positive for cytokeratins, variably expressed S100 protein, showed diffuse nuclear STAT6 positivity, and harbored NAB2::STAT6 gene fusions.
Polyembolokoilamania in Child Sexual Abuse
Authors: Donaruma-Kwoh Marcella M. , Weary Casey E. , Cruz Andrea T.
Published: February 2022

Objective

To characterize the physical examination findings in children and adolescents who disclosed insertion of an object into their bodies as part of their sexual abuse history and to identify how this population compares to similar cases described in the published literature.

Methods

This is a 15-year retrospective review of children younger than 18 years seen at a large urban children's assessment center. In addition, we reviewed and summarized the last two decades of literature characterizing pediatric anogenital foreign bodies to better understand previously described findings in similar populations.

Results

Sixty-eight children whose abuse histories included anal or genital insertion of a foreign body still presented with normal examination findings in the vast majority (89.7%) of cases, despite the diversity of items described. The literature on anogenital foreign bodies was sparse, offered a variety of approaches to the overall evaluation of such cases, and demonstrated inconsistent consideration of child sexual abuse in response to the diagnosis.

Conclusions

This article further supports the literature reflecting the overall rarity of abnormal anogenital findings in the clinical assessment for sexual abuse.
Vascularized Bone Flap Options for Complex Thoracic Spinal Reconstruction
Authors: Asaad Malke , Houdek Matthew T. , Huang Tony C. T. , Rose Peter S. , Moran Steven L.
Published: February 2022

Background:

Osseous reconstruction following total spondylectomy/vertebrectomy in the thoracic spine is indicated to restore spinal stability. To assist with bony reconstruction, vascularized bone flaps including free vascularized fibula flaps and pedicled rib flaps can be used. However, there are limited data comparing various techniques. The authors aimed to evaluate the outcomes of free vascularized fibula flaps and pedicled rib flaps used for thoracic spinal reconstruction.

Methods:

The authors reviewed 44 vascularized bone flaps [10 anterior pedicled rib flaps, 25 posterior pedicled rib flaps, and nine vascularized fibula flaps] for corpectomy defects spanning T1 to L1 between January of 1999 and June of 2018. Mean age and follow-up were 46 ±17 years and 74 ± 52 months, respectively.

Results:

The union rate was 93 percent, with a similar mean time to union among the three groups: free vascularized fibula flaps, 9 ± 4 months; anterior pedicled rib flaps, 9 ± 6 months; and posterior pedicled rib flaps, 9 ± 5 months (p = 0.95). Surgical-site complications were found in 27 vascularized bone flaps (61 percent), and reoperations and revisions were performed in 14 (32 percent) and 10 (23 percent) vascularized bone flaps, respectively. No differences were identified among anterior pedicled rib flaps, posterior pedicled rib flaps, and vascularized fibula flaps with regard to complication, reoperation, and revision rates.

Conclusions:

Free vascularized fibula flaps and pedicled rib flaps provide durable reconstruction for thoracic spinal defects. Union, time to union, revision, and reoperation rates were similar among anterior and posterior pedicled rib flaps and vascularized fibula flaps. Given the variability in indication and defect types among the flap cohorts, the authors’ results should be interpreted carefully as an insight into the outcomes of different vascularized bone flaps for the unique cases of thoracic spinal reconstruction rather than to compare the different flaps used.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A Comprehensive Approach for Measuring Spatial Deviations of Computer-Assisted Mandibular Reconstruction
Authors: Yang Wei-fa , Yu Peirong , Zhu Wang-yong , Choi Wing Shan , Pu Jingya Jane , Su Yu-xiong
Published: February 2022

Background:

Computer-assisted surgery has become the mainstream in mandibular reconstruction, but the lack of a standard measuring approach for spatial deviations of mandible hinders postoperative verification and the comparison of different subjects. This study aims to set up a comprehensive approach for measuring spatial deviations of computer-assisted mandibular reconstruction.

Methods:

A systematic review was conducted to extract all measurements for computer-assisted mandibular reconstruction. Thereafter, eligible measurements were included in the authors’ comprehensive approach, which categorized the measurements according to different anatomical structures and landmarks.

Results:

A total of 80 studies were included in the authors’ systematic review, and 31 measurements were extracted. The authors established a comprehensive panel of anatomical landmarks to facilitate measurement, including parts, points, lines, planes, and angles. These measurements encompassed spatial deviations of the overall mandible, condyle, gonial angle, bone grafts, midline, surgical plate, osteotomy, and miscellaneous indicators. A calculation spreadsheet was developed to collect landmarks and compute deviations automatically with built-in formulas. Finally, a simplified panel of measurements was recommended for spatial deviations of mandibular reconstruction.

Conclusions:

A comprehensive approach for measuring spatial deviations of computer-assisted mandibular reconstruction was established. Future studies will confirm this approach as an effective and scientific system for postoperative verification of computer-assisted mandibular reconstruction.
Intraoperative Navigation in Plastic Surgery with Augmented Reality: A Preclinical Validation Study
Authors: Rudy Hayeem L. , Schreiber Jillian S. , Wake Nicole , Lesko Robert P. , Gordon Alexandra , Garfein Evan S. , Tepper Oren M.
Published: February 2022

Background:

Augmented reality allows users to visualize and interact with digital images including three-dimensional holograms in the real world. This technology may have value intraoperatively by improving surgical decision-making and precision but relies on the ability to accurately align a hologram to a patient. This study aims to quantify the accuracy with which a hologram of soft tissue can be aligned to a patient and used to guide intervention.

Methods:

A mannequin’s face was marked in a standardized fashion with 14 incision patterns in red and nine reference points in blue. A three-dimensional photograph was then taken, converted into a hologram, and uploaded to HoloLens (Verto Studio LLC, San Diego, Calif.), a wearable augmented reality device. The red markings were then erased, leaving only the blue points. The hologram was then viewed through the HoloLens in augmented reality and aligned onto the mannequin. The user then traced the overlaid red markings present on the hologram. Three-dimensional photographs of the newly marked mannequin were then taken and compared with the baseline three-dimensional photographs of the mannequin for accuracy of the red markings. This process was repeated for 15 trials (n = 15).

Results:

The accuracy of the augmented reality-guided intervention, when considering all trials, was 1.35 ± 0.24 mm. Markings that were positioned laterally on the face were significantly more difficult to reproduce than those centered around the facial midline.

Conclusions:

Holographic markings can be accurately translated onto a mannequin with an average error of less than 1.4 mm. These data support the notion that augmented reality navigation may be practical and reliable for clinical integration in plastic surgery.