bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016–2023*
Authors: Rodriguez Katherine M. , Vaught Jordan , Salz Lisa , Foley Jennifer , Boulil Zaineb , Van Dongen-Trimmer Heather M. , Whalen Drewann , Oluchukwu Okonkwo , Liu Kuang Chuen , Burton Jennifer , Syngal Prachi , Vargas-Shiraishi Ofelia , Kingsmore Stephen F. , Sanford Kobayashi Erica , Coufal Nicole G. 
Published: April 2024

OBJECTIVES:
Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions.

DESIGN:
Ambidirectional multisite cohort study.

SETTING:
Four tertiary children’s hospitals.

PATIENTS:
Children 0–18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo–4.6 yr). Median time for return of preliminary results was 3 days (IQR 2–4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8–105]) and congenital heart disease (OR 4.2 [95% CI, 1.3–16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5–62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76–0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02).

CONCLUSIONS:
In this 2016–2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51–67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.
Effects of Chronic Pain Diagnoses on the Antidepressant Efficacy of Transcranial Magnetic Stimulation
Authors: Afshar Houtan Totonchi , Fishbein Joel N. , Martinez Erica J. , Chu Gage M. , Shenasa Mohammad A. , Ramanathan Dhakshin , Herbert Matthew S. 
Published: April 2024

ABSTRACT

Objective
Major depressive disorder (MDD) and chronic pain are highly comorbid and bidirectionally related. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex is effective in treating MDD, but additional research is needed to determine if chronic pain interferes with rTMS for MDD.

Methods
Participants were 124 veterans (M
age = 49.14, SD = 13.83) scheduled for 30 sessions of rTMS across 6 weeks. Depression severity was monitored weekly using the Patient Health Questionnaire-9 (PHQ-9). Having any pain diagnosis, low back pain, or headache/migraine were assessed by chart review. We fit latent basis models to estimate total change by pain diagnosis in depression scores and quadratic latent growth models to examine differences in growth rates. Then, we computed χ
2 tests of group differences in response (PHQ-9 reduction ≥50%) and remission rates (final PHQ-9 < 5).

Results
A total of 92 participants (74%) had a documented pain diagnosis, 58 (47%) had low back pain, and 32 (26%) had headache/migraine. In growth models, depression scores initially decreased (linear slope estimate = −2.04, SE = 0.26, p < .0001), but the rate of decrease slowed over time (quadratic slope estimate = 0.18, SE = 0.04, p < .001). Overall change was not different as a function of any pain diagnosis (p = .42), low back pain (p = .11), or headache/migraine (p = .28). However, we found that low back pain was a negative predictor of response (p = .032).

Conclusions
These data support rTMS as a viable treatment option for comorbid populations. Although patients with comorbid chronic pain conditions are likely to receive benefit from rTMS for depression, adjunctive pain treatment may be indicated.
Unconscious Activation of Negative Emotional Memories Increases Pain Unpleasantness
Authors: Frisch Stephan , Walter Steffen , Rebhann Vanessa , Gruss Sascha , Geisel Daniela , Bär Karl-Jürgen , Gündel Harald , Lane Richard D. , Smith Ryan 
Published: April 2024

ABSTRACT

Objective
The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall).

Methods
Seventy-two healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral and 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial.

Results
Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative versus neutral images (5.52 [SD = 2.06] versus 5.23 [SD = 2.10]; p = .02). This pattern was also present when comparing cues to remembered negative versus neutral images (5.62 [SD = 1.94] versus 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative versus neutral images when remembered (5.48 [SD = 1.79] versus 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] versus 5.16 [SD = 1.93]; p = .30).

Conclusions
Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to nonrecallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions.
Squamous Cell Carcinoma Arising From Epidermal Cyst
Authors: Kim Ji-Young , Min Sally , Park Joseph Kyu-hyung , Kim Sang Wha 
Published: April 2024

Abstract
Epidermal cysts are among the most common benign subcutaneous tumors. However, malignant transformation of benign epidermal cysts into squamous carcinomas has been reported. Owing to its low incidence rate, the clinical and pathological features of this condition are not well understood. This study aimed to analyze the clinical and pathological characteristics of the malignant transformation of epidermal cysts, which could suggest an appropriate treatment strategy. We conducted a retrospective study of 9 patients diagnosed with squamous cell carcinoma arising from epidermal cysts. All patients underwent surgical excision, and clinical information regarding patient demographics, tumor characteristics, treatment, and outcomes was analyzed. The average age at diagnosis was 57.3 years, with an average latency period of 15.4 years. Five patients had undergone prior cyst excision or drainage, with an average of 2.3 episodes of recurrence. Surgical excision was the primary treatment in all cases, and 2 patients with margin involvement at the final pathology underwent re-excision with additional resection margins. No recurrence was observed during the follow-up period. Four patients had immune dysregulation due to an underlying chronic kidney disease or cancer. Our study emphasizes the need for increased awareness of squamous cell carcinoma arising from epidermal cysts in patients with a history of cyst existence or recurrence, especially those with immune deficiencies. We expect these findings to contribute to early suspicion of malignant transformation and guide adequate clinical decision-making.
Optimal Treatment Order With Fibula-Free Flap Reconstruction, Oncologic Treatment, and Dental Implants: A Systematic Review and Meta-Analysis
Authors: Sriram Shreya , Njoroge Moreen W. , Lopez Christopher D. , Zhu Lily , Heron Matthew J. , Zhu Katherine J. , Yusuf Cynthia T. , Yang Robin 
Published: April 2024

Head and neck cancer (HNC) patients benefit from craniofacial reconstruction, but no clear guidance exists for rehabilitation timing. This meta-analysis aims to clarify the impact of oncologic treatment order on implant survival. An algorithm to guide placement sequence is also proposed in this paper. PubMed, Embase, and Web of Science were searched for studies on HNC patients with ablative and fibula-free flap (FFF) reconstruction surgeries and radiotherapy (RTX). Primary outcomes included treatment sequence, implant survival rates, and RTX dose. Of 661 studies, 20 studies (617 implants, 199 patients) were included. Pooled survival rates for implants receiving >60 Gy RTX were significantly lower than implants receiving < 60 Gy (82.8% versus 90.1%, P=0.035). Placement >1 year after RTX completion improved implant survival rates (96.8% versus 82.5%, P=0.001). Implants receiving pre-placement RTX had increased survival with RTX postablation versus before (91.2% versus 74.8%, P<0.001). One hundred seventy-seven implants were placed only in FFF with higher survival than implants placed in FFF or native bone (90.4% versus 83.5%, P=0.035). Radiotherapy is detrimental to implant survival rates when administered too soon, in high doses, and before tumor resection. A novel evidence-based clinical decision-making algorithm was presented for utilization when determining the optimal treatment order for HNC patients. The overall survival of dental prostheses is acceptable, reaffirming their role as a key component in rehabilitating HNC patients. Considerations must be made regarding RTX dosage, timing, and implant location to optimize survival rates and patient outcomes for improved functionality, aesthetics, and comfort.
Optimizing the Management Strategies of Delayed Post-Pancreaticoduodenectomy Hemorrhage
Authors: Ma Tao , Qian Tao , Huang Kaiquan , Li Huiliang , Lin Wei-Chiao , Lao Mengyi , Gao Shunliang , Bai Xueli , Liang Tingbo 
Published: April 2024

Objective:
To optimize the management strategies of delayed post-pancreaticoduodenectomy hemorrhage (PPH) by evaluating data from a high-volume pancreatic center.

Summary Background Data:
Delayed PPH is a potentially lethal complication. The management of delayed PPH remains controversial.

Methods:
Patients who underwent pancreaticoduodenectomy between July 2018 and June 2023 were identified from an institutional database. The clinical scenarios, management, and outcomes of patients with delayed PPH (>5 d postoperatively) were analyzed.

Results:
Out of the 2013 patients who underwent elective pancreaticoduodenectomy, 130 (6.5%) with delayed PPH were identified. The overall mortality was 15.4%. The success rates of endoscopy, angiographic intervention, and relaparotomy in treating delayed PPH were 54.5%, 56.5%, and 68.8%, respectively. For PPH from the hepatic arteries or their branches, complete blockade of the common or proper hepatic artery (C/PHA) was performed in 17 patients, either by coil embolization (n=7) or surgical ligation (n=10). Coil embolization of the C/PHA resulted in significant infarction of the left liver in 2 patients. No postoperative liver infarction occurred in patients who underwent ligation of the C/PHA during relaparotomy. Ten patients underwent suture repair of the C/PHA 13 times during relaparotomy. Arterial ligation achieved a significantly higher success rate of hemostasis than suture repair of the C/PHA during relaparotomy (100% vs. 30.8%, P<0.001).

Conclusions:
Angiography should be attempted first in managing hemodynamically stable delayed PPH. Arterial ligation was preferred for bleeding from the hepatic arteries during relaparotomy with minor consequences for the liver.
Pretransplant Malnutrition, Particularly With Muscle Depletion Is Associated With Adverse Outcomes After Kidney Transplantation
Authors: Lorden Heather , Engelken Jessa , Sprang Katrina , Rolfson Megan , Mandelbrot Didier , Parajuli Sandesh 
Published: April 2024

Background.
Kidney transplant centers lack consistent diagnostic malnutrition tools. The Academy of Nutrition and Dietetics and American Society of Parenteral Nutrition Adult Malnutrition Criteria (AMC) is the widely accepted and utilized tool by Registered Dietitian Nutritionists (RDNs) to diagnose malnutrition.

Methods.
In this single-center, retrospective observational study, we evaluated the outcomes of prekidney transplant malnutrition based on Academy of Nutrition and Dietetics and American Society of Parenteral Nutrition AMC, as well as the individual components of the AMC, on posttransplant outcomes including length of stay, delayed graft function (DGF), early readmission, cardiovascular events, acute rejection, death-censored graft failure, and death. Bivariable and multivariable logistic regression models were used to assess the association of malnutrition or its components with outcomes of interest.

Results.
A total of 367 recipients were included, of whom 36 (10%) were malnourished (23 moderately and 13 severely) at pretransplant evaluation. In adjusted models, pretransplant malnutrition was significantly associated with increased risk for early readmission (adjusted odds ratio 2.86; 95% confidence interval: 1.14-7.21; P = 0.03) and with DGF (adjusted odds ratio 8.33; 95% confidence interval: 1.07-64.6; P = 0.04). Muscle depletion was also associated with an increased risk for readmission and with DGF. Fat depletion and reduced functionality in the adjusted model were only associated with increased risk for readmission.

Conclusions.
Malnutrition could be an important consideration for selecting kidney transplant recipients because it was associated with poor clinical outcomes. A multidisciplinary approach with the involvement of RDNs to outline a nutrition intervention plan may help mitigate some of the poor outcomes.
Streptococcus pyogenespharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections
Authors: Osowicki Joshua , Frost Hannah R , Azzopardi Kristy I , Whitcombe Alana L , McGregor Reuben , Carlton Lauren H. , Baker Ciara , Fabri Loraine , Pandey Manisha , Good Michael F , Carapetis Jonathan R. , Walker Mark J , Smeesters Pierre R , Licciardi Paul V , Moreland Nicole J , Hill Danika L , Steer Andrew C 
Published: April 2024

AbstractKnowledge gaps regarding human immunity toStreptococcus pyogeneshave impeded vaccine development. To address these gaps and evaluate vaccine candidates, we established a human challenge model ofS. pyogenespharyngitis. Here, we analysed antibody responses in serum and saliva against 19 antigens to identify characteristics distinguishing 19 participants who developed pharyngitis and 6 who did not. Pharyngitis elicited serum IgG responses to key vaccine antigens and a muted mucosal IgA response, whereas the 6 participants without pharyngitis had more pronounced IgA responses and minimal IgG responses. Serum IgG responses to pharyngitis in adult participants resembled those observed in children and were inversely correlated with the magnitude of pre-existing responses. While a straightforward correlate of protection was not evident, baseline antibody signatures distinguished clinical and immunological outcomes following experimental challenge. This highlights the influence of a complex humoral imprint from previous exposure, relevant for interpreting immunogenicity in forthcoming vaccine trials.
An adapted typology of tree-related microhabitats including tropical forests
Authors: Nußer Ronja , Bianco Giovanni , Kraus Daniel , Larrieu Laurent , Feldhaar Heike , Schleuning Matthias , Müller Jörg 
Published: April 2024

AbstractTree-related microhabitats (TreMs) describe the microhabitats that a tree can provide for a multitude of other taxonomic groups and have been proposed as an important indicator for forest biodiversity (Asbeck et al., 2021). So far, the focus of TreM studies has been on temperate forests, although many trees in the tropics harbour exceptionally high numbers of TreMs. In this study, TreMs in the lowland tropical forests of the Choco (Ecuador) and in the mountain tropical forests of Mount Kilimanjaro (Tanzania) were surveyed. Our results extend the existing typology of TreMs of Larrieu et al. (2018) to include tropical forests and enabled a comparison of the relative recordings and diversity of TreMs between tropical and temperate forests. A new TreM form, Root formations, and three new TreM groups, concavities build by fruits or leaves, dendrotelms, and root formations, were established. In total, 15 new TreM types in five different TreM groups were specified. The relative recordings of most TreMs were similar between tropical and temperate forests. However,ivy and lianas,andfernswere more common in the lowland rainforest than in temperate forests, andbark microsoil,limb breakage,andfoliose and fruticose lichensin tropical montane forest than in lowland rainforest. Mountain tropical forests hosted the highest diversity for common and dominant TreM types, and lowland tropical forest the highest diversity for rare TreMs. Our extended typology of tree-related microhabitats can support studies of forest-dwelling biodiversity in tropical forests. Specifically, given the ongoing threat to tropical forests, TreMs can serve as an additional tool allowing rapid assessments of biodiversity in these hyperdiverse ecosystems.
Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline
Authors: Cheng Keren , Seita Yasunari , Whelan Eoin C. , Yokomizo Ryo , Hwang Young Sun , Rotolo Antonia , Krantz Ian D. , Kaur Maninder , Ginsberg Jill P. , Lal Priti , Luo Xunda , Pierorazio Phillip M. , Linn Rebecca L. , Ryeom Sandra , Sasaki Kotaro 
Published: April 2024

SummaryAberrant male germline development can lead to the formation of seminoma, a testicular germ cell tumor. Seminomas are biologically similar to primordial germ cells (PGCs) and many bear an isochromosome 12p [i(12p)] with two additional copies of the short arm of chromosome 12. By mapping seminoma transcriptomes and open chromatin landscape onto a normal human male germline trajectory, we find that seminoma resembles premigratory/migratory primordial germ cells, but exhibit enhanced germline and pluripotency programs, and upregulation of genes involved in apoptosis, angiogenesis, and MAPK/ERK pathways. Using pluripotent stem cell-derived PGCs from Pallister Killian syndrome patients mosaic for i(12p) to model seminoma, we identify gene dosage effects that may contribute to transformation. As murine seminoma models do not exist, our analyses provide critical insights into genetic, cellular and signaling programs driving seminoma transformation, and the newly developed in vitro platform permits evaluation of additional signals required for seminoma tumorigenesis.
FInCH: FIJI plugin for automated and scalable whole-image analysis of protein expression and cell morphology
Authors: Lee Cody A. , Moreno Carmen Sánchez , Badyaev Alexander V. 
Published: April 2024

AbstractStudy of morphogenesis and its regulation requires analytical tools that enable simultaneous assessment of processes operating at cellular level, such as synthesis of transcription factors (TF), with their effects at the tissue scale. Most current studies conduct histological, cellular and immunochemical (IHC) analyses in separate steps, introducing inevitable biases in finding and alignment of areas of interest at vastly distinct scales of organization, as well as image distortion associated with image repositioning or file modifications. These problems are particularly severe for longitudinal analyses of growing structures that change size and shape. Here we introduce a python-based application for automated and complete whole-slide measurement of expression of multiple TFs and associated cellular morphology. The plugin collects data at customizable scale from the cell-level to the entire structure, records each data point with positional information, accounts for ontogenetic transformation of structures and variation in slide positioning with scalable grid, and includes a customizable file manager that outputs collected data in association with full details of image classification (e.g., ontogenetic stage, population, IHC assay). We demonstrate the utility and accuracy of this application by automated measurement of morphology and associated expression of eight TFs for more than six million cells recorded with full positional information in beak tissues across 12 developmental stages and 25 study populations of a wild passerine bird. Our script is freely available as an open-source Fiji plugin and can be applied to IHC slides from any imaging platforms and transcriptional factors.Graphical abstractSpecifications table
The effects of parasitism on sex allocation of a hermaphroditic acorn barnacle
Authors: Tamechika Masami M. , Yamada Hiroyuki , Ijiri Shigeho , Yusa Yoichi 
Published: April 2024

AbstractSex allocation theory predicts the adaptive allocation of resources to male versus female reproduction in simultaneous hermaphrodites in response to individual characteristics or environmental factors. Because parasites uptake resources from their hosts, their presence could affect the sex allocation of the hosts. We investigated the effects of infestation status and infestation intensity by the rhizocephalan barnacleBoschmaella japonicaon reproduction, including sex allocation, of the host intertidal barnacleChthamalus challengeri. Feeding activity was also examined as a factor related to resource intake. Both male and female reproductive investment decreased with increasing parasite infestation, and the sex allocation of large infested hosts was more male-biased than that of large uninfested hosts. Moreover, in contrast to the model prediction that male investment does not change under resource limitation, male investment decreased in infested hosts whose resources were taken by parasites. This reduction in male investment could be explained by changes in mating group size, since infested hosts have shorter penises and consequently are able to access fewer mating partners.
Scale-free dynamics of cerebrospinal fluid regions is associated with Alzheimer’s disease-related pathology
Authors: Guo Qiwei , Hua Lin , Zhao Zhiying , Yuan Zhen 
Published: April 2024

AbstractCerebrospinal Fluid (CSF) clearance is one of the central mechanisms for removal of amyloid-β (Aβ) and tau proteins from the central nervous system that are closely linked to Alzheimer’s Disease (AD) pathology. Conventional functional imaging studies in AD have primarily focused on activities in the brain while ignoring macroscopic cerebrospinal fluid (CSF) activities. In the current study, we utilized a public dataset from the Alzheimer’s Disease Neuroimaging Initiative. Our analysis spanned both brain and cerebrospinal fluid (CSF) areas. We compared the scale-free dynamics in fMRI signals across three groups: cognitively normal individuals (CN), people with Alzheimer’s Disease (AD), and those with mild cognitive impairments (MCI). Scale-free dynamics are patterns of brain activity that remain consistent across different time scales. Our comparison focused on the Hurst exponent (H), a measure derived from detrended fluctuation analysis (DFA), to characterize these dynamics. This comparison revealed clusters in the fourth ventricle and subarachnoid space (medioventral channel along the spinal axis). In these CSF-filled structures, H was significantly higher in AD group comparing to CN. Moreover, H in these two clusters correlated with AD pathological biomarkers including CSF Aβ and tau in the AD group. These findings suggested scale-free properties of macroscopic CSF flow as a potential imaging biomarker for AD. This biomarker can be readily acquired from common resting-state fMRI scans and therefore may be valuable for AD diagnosis.