bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updates on the diagnostic evaluation, genotype–phenotype correlation, and treatments of genetic epilepsies
Authors: Zimmern Vincent , Korff Christian 
Published: September 2022

Purpose of review
This article reviews the latest publications in genetic epilepsies, with an eye on publications that have had a translational impact. This review is both timely and relevant as translational discoveries in genetic epilepsies are becoming so frequent that it is difficult for the general pediatrician and even the general child neurologist to keep up.

Recent findings
We divide these publications from 2021 and 2022 into three categories: diagnostic testing, genotype–phenotype correlation, and therapies. We also summarize ongoing and upcoming clinical trials.

Summary
Two meta-analyses and systematic reviews suggest that exome and genome sequencing offer higher diagnostic yield than gene panels. Genotype–phenotype correlation studies continue to increase our knowledge of the clinical evolution of genetic epilepsy syndromes, particularly with regards to sudden death, auditory dysfunction, neonatal presentation, and magnetoencephalographic manifestations. Pyridoxine supplementation may be helpful in seizure management for various genetic epilepsies. There has been interest in using the neurosteroid ganaxolone for various genetic epilepsy syndromes, with clear efficacy in certain trials. Triheptanoin for epilepsy secondary to glucose transporter 1 (GLUT1) deficiency syndrome is not clearly effective but further studies will be needed.
Histological patterns, subtypes and aspects of prostate cancer: different aspects, different outcomes
Authors: Wasinger Gabriel , Oszwald André , Shariat Shahrokh F. , Compérat Eva 
Published: September 2022

Purpose of review
The most common prostatic cancers (PCa) are acinary adenocarcinomas. Histological subtypes have been variably defined. The purpose of this review is to discuss unusual histological patterns and subtypes of acinar adenocarcinoma, as well as other types of PCa and their prognostic and therapeutic relevance.

Recent findings
The new term ‘subtype’ for morphologically defined tumor entities replaced the term ‘variant’ in the new 2022 classification of the WHO to allow for clear terminological distinction from genetic variants. The 2022 WHO classification mentions prostatic intraepithelial neoplasia (PIN)-like carcinoma, signet-cell-like adenocarcinoma, sarcomatoid carcinoma and pleomorphic-giant-cell adenocarcinoma of the prostate as true subtypes of acinary PCa. Other forms of acinary PCa are termed unusual histological patterns and include atrophic, foamy-cell, microcystic, pseudohyperplastic and mucinous patterns. Nonacinar forms of prostate cancer include other glandular PCa, the ductal adenocarcinoma and the treatment-associated neuroendocrine carcinoma, and nonglandular PCa, the adenosquamous carcinoma, the squamous cell carcinoma and the adenoid cystic (basal cell) carcinoma of the prostate.

Summary
True subtypes of acinary PCa and other forms of glandular and nonglandular PCa show relevant differences in prognosis and treatment approach compared with classic acinary PCa. The relevance of unusual histological patterns mainly lies in their deceptive benign appearance and the need for pathologists to know about these entities for accurate and timely diagnosis.
Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN
Authors: Yerushalmy-Feler Anat , Pujol-Muncunill Gemma , Martin-de-Carpi Javier , Kolho Kaija-Leena , Levine Arie , Olbjørn Christine , Granot Maya , Bramuzzo Matteo , Rolandsdotter Helena , Mouratidou Natalia , Hradsky Ondrej , Scarallo Luca , Matar Manar , Rimon Ramit Magen , Rinawi Firas , Shalem Tzippi , Najajra Hisham , de Meij Tim , Aloi Marina , Rodríguez-Belvís Marta Velasco , Alvisi Patrizia , Schneider Anna-Maria , van Rheenen Patrick , Navas-López Víctor Manuel , Kiparissi Fevronia , Barrio Josefa , Turner Dan , Cohen Shlomi 
Published: September 2022

Objectives:Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD.Methods:This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up.Results:Sixty-nine children were included (median age 15.8 years, interquartile range 13.8–16.9) with median disease duration of 4.3 years (2.9–6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation (P= 0.001). The median C-reactive protein level decreased from 14 (3–28.03) to 5 (1.1–20.5) mg/L (P= 0.012), and the fecal calprotectin level from 1100 (500–2300) to 515 (250–1469) µg/g (P= 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported.Conclusions:Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.
The Five-4-Life Quality Improvement Program
Authors: Bala-Kerr Ruth , Sullivan Brittany , Martin Shelley 
Published: September 2022

Background:
Poor leadership and teamwork in cardiopulmonary resuscitation (CPR) are associated with poor patient outcomes.

Problem:
Frontline nursing staff frequently identify patients in cardiac arrest but may not have the initial leadership and teamwork skills to organize their initial rescue response.

Approach:
The Five-4-Life Quality Improvement (QI) program was pilot tested in a pediatric unit within a 510-bed acute care hospital in 2 phases: first, an educational program focused on leadership, team dynamics, and CPR skills, followed by sustaining interventions in the unit. Video recordings of 12 mock codes (4 pre-, 4 post-, 4 follow-up) were analyzed by trained observers.

Outcomes:
Descriptive statistical tests indicated a significant improvement in leadership, teamwork, and task management scores pre- and post-program, and sustained after the program.

Conclusion:
Implementing the Five-4-Life QI program is feasible in improving leadership, teamwork, and task management of first responding frontline nurses.
Is leg-driven treadmill-based exoskeleton robot training beneficial to post-stroke patients: A systematic review and meta-analysis
Authors: Zhu Ying-Hui , Ruan Ming , Yun Rui-Sheng , Zhong Ying-Xi , Zhang Yu-Xin , Wang Yong-Jun , Sun Yue-Li , Cui Jia-Wen 
Published: September 2022

Abstract

Objective
To systematically review the effects of leg-driven treadmill-based exoskeleton robot training on balance and walking ability in post-stroke patients.

Design
The PubMed, Cochrane Library, Embase, Web of Science, Medline, CNKI, VIP, and Wanfang databases were searched from inception to August 2021. The literature quality was evaluated using Cochrane Handbook. Primary outcomes include the functional ambulation category scale (FAC) and Berg Balance Scale (BBS), and secondary outcomes include the 10-m time walking test (10TWT), 6-m walking test (6MWT), and gait assessment cadence were analyzed.

Results
Seventeen randomized controlled trials were included in the systematic review, 15 studies in meta-analysis. Primary outcomes showed no significant difference in the FAC score; subgroup with the exoskeleton robot + conventional therapy of the BBS score was significantly increased; secondary outcomes showed no significance in 6MWT or 10TWT. The cadence score increased for the subgroup with an onset of >6 months in the treatment group. The control group performed better than the subgroup with an onset of <6 months.

Conclusion
Leg-driven treadmill-based exoskeleton robot training can improve balance function in poststroke patients and is beneficial for patients with an onset of >6 months. However, there is no evidence to support the efficacy of walking ability.
De Novo Extramedullary Plasmacytoma of Thyroid Cartilage
Authors: Gupta Manoj , Pasricha Sunil , Ahmed Rayaz , Khoda Jeevitesh , Choudhury Partha Sarathi 
Published: September 2022

Abstract
Myeloma involving the laryngeal cartilage is rare, whereas extramedullary plasmacytoma involving only the thyroid cartilage is even rarer. No case of de novo extramedullary plasmacytoma involving thyroid cartilage has been published so far. Hence, it was a diagnostic challenge for clinicians, radiologists, and pathologists. Here, we presented a case of a 61-year-old man who had fixed right laryngeal swelling. After 18F-FDG PET/CT, biopsy, and myeloma workup, it was found to be plasmacytoma involving the right thyroid cartilage lamina. This case highlighted the rarity of this presentation and the importance of keeping in mind this differential to lead toward diagnosis.
Mesenteric Mesonephric Adenocarcinoma on 68Ga-FAPI PET/CT
Authors: Liu Huipan , Chen Yue 
Published: September 2022

AbstractMesenteric mesonephric adenocarcinoma is an uncommon mesenteric neoplasm, which was arising from the mesonephric remnant of the female reproductive tract. Herein, we report the68Ga-FAPI PET/CT findings in a 66-year-old woman with mesenteric mesonephric adenocarcinoma.
Feasible Removal of Facial Hemangiomas Under Local Anesthesia in Young Children
Authors: Hazkour Nissim , Palacios Jose , Othman Sammy , Smith Jacob D. , Goote Paige , Bastidas Nicholas 
Published: September 2022

Background:
Facial Hemangiomas are often recommended to be removed exclusively in the operating room under general anesthesia, especially for children under the age of 4. Assumed parental and patient anxiety and possible blood loss pushes surgeons away from attempting excision under local anesthesia.

Methods:
A review was conducted to assess the outcomes of children who underwent excision of facial hemangiomas under local anesthesia alone by 1 plastic surgeon with a minimum of 3 months follow-up. Complications and hemangioma recurrence were recorded. A survey was given 3 to 6 months after treatment to assess parental satisfaction, anxiety, and thought process about anesthesia.

Results:
Eighteen children (9 males and 9 females) underwent in-office excision between 2020 and 2021. The mean age of this cohort was 12 months ( ranging 2–52 m). The average facial hemangioma size was 2.088 cm (ranging 1.0–3.2 cm). Ten patients experienced complete resolution (56%) at 12-month follow-up. There were no hospitalizations or cases of significant (>10 mL) blood loss, infection, dehiscence, hematoma, or scar hypertrophy. The average level of parental anxiety before the procedure was 3.3/10, and 1.6/10 after the procedure. Total 13/14 parents gave 4/4 ratings for satisfaction with the quality of care, team responsiveness, pain management, and management of expectations.

Conclusions:
Facial hemangioma removal under local anesthesia alone is a safe and feasible alternative treatment method for patients younger than 4 years of age.
Assessing the Nasal Midline in Rhinoplasty: How Good Are We?
Authors: DeSerres Joshua J. , Fishman Zachary , Whyne Cari M. , Kiss Alex , Fialkov Jeff A. 
Published: September 2022

Background:
The challenge of assessing nasal alignment and asymmetry can contribute to high revision rates in rhinoplasty. Comparing to a validated computer algorithm for nasal alignment, the accuracy with which plastic surgeons can assess deviation of the nasal midline from the facial midline was measured.

Methods:
Using 20 faces from the Binghamton University 3-dimensional face database, deviation was evaluated from facial midline of the middorsal line for the upper, middle, and lower thirds of the nose. Surgeons were asked to assess extent of deviation from facial midline for each third of the nose using a linear analog scale. Spearman correlations were performed comparing the surgeons’ results to the algorithm measurements. Eleven residents and 9 consultant surgeons were tested.

Results:
Surgeons’ assessment of deviation correlated poorly with the algorithm in the upper third (r=0.32, P<0.0001) and moderately in the middle third (r=0.49, P<0.0001) and lower third (r=0.41, P<0.0001) of the nose. No difference in accuracy was found between trainee and consultant surgeons (P=0.51), and greater experience (>10 y performing nasal surgery) did not significantly affect performance (P=0.15). The effect of fatigue on the accuracy of assessment was found to be significant (P=0.0009).

Conclusions:
Surgeons have difficulty in visually assessing the 3-dimensional nasal midline irrespective of experience, and surgeon fatigue was found to be adversely affect the accuracy of assessments.
The Most Cost-Efficient And Effective Set Of Covid-19 Policies To Reduce Monthly Covid-19 Case Increase Rates
Authors: Chen Charline 
Published: September 2022

AbstractThe coronavirus is one of the most unprecedented pandemics in recent decades. Countries have been struggling to identify the appropriate policies to prevent COVID-19 spread efficiently. As coronavirus case and death numbers fluctuated among countries in the past two years, questions of which policies are most cost-efficient and effective in preventing coronavirus spread have yet to be answered. There are no worldwide agreed guidelines to follow, to the author’s best knowledge. Countries are prone to making policy and implementation errors that could cost lives and cause tremendous economic loss. Although much research on COVID-19 has been done and many focused on policy effectiveness, few focused on the cost-efficiency and effectiveness of COVID-19 policies. This research identifies the most Cost-Efficient and Effective Set of COVID-19 Policies to Reduce Monthly COVID-19 Case Increase Rates through a quantitative, big-data-driven, and machine-learning enabled approach. The research collected and analyzed 13 COVID-19 policies and associated daily COVID-19 case numbers across 180 countries from January 2020 to June 2021, developed Policy Cost Model, defined Policy Efficiency and Effectiveness Index, and developed a Fully-Automated Best Policy Group Finder Python Program to find the most cost efficient and effective policy group. This research found that 1) Before Vaccinations are available, the most cost-efficient and effective policy group includes Facial Covering, Testing Policy, and Contact Tracing. Its cost-efficiency is a 1% monthly case decrease rate per billion of dollars spent. Its effectiveness is a 37% monthly case decrease rate. It is 1474 times more cost-efficient, 11 times more effective, and costs around $5336.83 Billion less than implementing all 12 common COVID-19 policies as the U.S. and many other countries did before vaccinations were available; 2) After Vaccinations are available, the most cost-efficient and effective policy group includes Facial Coverings, Contact Tracing, and Vaccinations. Its cost-efficiency is a 2.7% monthly case decrease rate per billion of dollars spent. Its effectiveness is a 52% monthly case decrease rate. It is 3835 times more cost-efficient, 21.5 times more effective, and costs around $5350 Billion less than implementing all 13 common COVID-19 policies as the U.S. and many other countries did. The research results will help countries, especially underdeveloped ones with very limited budgets, to identify and implement the most cost-efficient and effective policies so they can spend much less but reduce monthly cases much more.
Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants
Authors: Jetsonen Elias , Didio Giuliano , Winkel Frederike , Pou Maria Llach , Boj Chloe , Kuczynski-Noyau Laura , Võikar Vootele , Guirado Ramon , Taira Tomi , Lauri Sari E. , Castren Eero , Umemori Juzoh 
Published: September 2022

SummaryCritical period-like plasticity (iPlasticity) can be reinstated in the adult brain by several interventions, including drugs and optogenetic modifications. We have demonstrated that a combination of iPlasticity with optimal training improves behaviors related to neuropsychiatric disorders. In this context, the activation of TrkB, a receptor for BDNF, in Parvalbumin positive (PV+) interneurons has a pivotal role in cortical network changes. However, it is unknown if the activation of TrkB in PV+ interneurons is important for other plasticity-related behaviors, especially for learning and memory. Here, using mice with heterozygous conditional TrkB deletion in PV+ interneurons (PV-TrkB hCKO) in Intellicage and fear erasure paradigms, we show that chronic treatment with fluoxetine, a widely prescribed antidepressant drug that is known to promote the activation of TrkB, enhances behavioral flexibility in spatial and fear memory, largely depending on the expression of the TrkB receptor in PV+ interneurons. In addition, hippocampal long-term potentiation (LTP) was enhanced by chronic treatment with fluoxetine in wild-type mice, but not in PV-TrkB hCKO mice. Transcriptomic analysis of PV+ interneurons after fluoxetine treatment indicated intrinsic changes in synaptic formation and downregulation of enzymes involved in perineuronal net (PNN) formation. Consistently, immunohistochemistry has shown that the fluoxetine treatment alters PV expression and reduces PNNs in PV+ interneurons, and here we show that TrkB expression in PV+ interneurons is required for these effects. Together, our results provide molecular and network mechanisms for the induction of critical period-like plasticity in adulthood.
The thermoception task: a thermal-imaging based procedure for measuring awareness of changes in peripheral body temperature
Authors: Vabba Alisha , Panasiti Maria Serena , Scattolin Marina , Spitaleri Marco , Porciello Giuseppina , Aglioti Salvatore Maria 
Published: September 2022

AbstractAlthough thermal body signals provide crucial information about the state of an organism, and changes in body temperature may be a sign of affective states (e.g., stress, pain, sexual arousal), research on thermal awareness is limited. Here we developed a task measuring awareness of changes in peripheral body temperature (thermal interoception) and compared it to the classical heartbeat counting task (cardiac interoception). With an infrared lightbulb we delivered stimuli of different temperature intensities to the right hand of 31 healthy participants. Thermal interoceptive accuracy, i.e., the difference between participants’ real and perceived change in hand temperature, showed good inter-individual variability. We found that thermal interoception did not correlate with (and was generally higher than) cardiac interoception, suggesting that different interceptive channels provide separate contributions to awareness of bodily states. Moreover, the results hint at the great salience of thermal signals and the need for thermoregulation in day-to-day life. Finally, thermal interoceptive accuracy was associated with self-reported awareness of body temperature changes, and with the ability to regulate distress by focusing on body sensations. Our task has the potential to significantly increase current knowledge about the role of interoception in cognition and behavior, particularly in social and emotional contexts.
The Sw-5b NLR immune receptor induces earlier transcriptional changes in response to thrips-mediated inoculation of Tomato spotted wilt orthotospovirus compared to mechanical inoculation
Authors: Ordaz Norma A. , Nagalakshmi Ugrappa , Boiteux Leonardo S. , Atamian Hagop S. , Ullman Diane E. , Dinesh-Kumar Savithramma P. 
Published: September 2022

ABSTRACTThe nucleotide-binding leucine-rich repeat (NLR) class of immune receptor, Sw-5b confers resistance to Tomato spotted wilt orthotospovirus (TSWV). Although Sw-5b is known to activate immunity upon recognition of the NSm of TSWV, we know very little about the downstream events that lead to resistance. Here, we investigated the early transcriptomic changes that occur in response to both mechanical and thrips-mediated inoculation of TSWV using near-isogenic resistant and susceptible tomato lines. Interestingly, the Sw-5b induces earlier transcriptional changes in response to thrips-mediated inoculation compared to mechanical inoculation of TSWV. A subset of the differentially expressed genes (DEGs) observed at 12 and 24 hours post thrips-mediated inoculation of TSWV was only present at 72 hours post mechanical inoculation. Although some DEGs were shared between thrips and mechanical inoculation at 72 hours postinfection, many DEGs were specific to either thrips-mediated or mechanical inoculation of TSWV. In response to thrips-mediated inoculation, an NLR immune receptor, cysteine-rich receptor-like kinase, G-type lectin S-receptor-like kinases, and transcription factors such as the ethylene response factor 1 and the calmodulin-binding protein 60 were induced. Whereas, in response to mechanical inoculation, fatty acid desaturase 2-9, cell death genes, DCL2b, RIPK/PBL14-like, and transcription factors such as ERF017 and WRKY75 were differentially expressed. Our findings reveal novel insights into Sw-5b responses specific to the method of TSWV inoculation. Given that TSWV is transmitted in nature primarily by the thrips, the DEGs we have identified provide a foundation for understanding the mechanistic roles of these genes in the Sw-5b-mediated resistance.
Environmental profiles of urban living relate to regional brain volumes and symptom groups of mental illness through distinct genetic pathways
Authors: Xu Jiayuan , Liu Nana , Polemiti Elli , Mondragon Liliana Garcia , Tang Jie , Liu Xiaoxuan , Lett Tristram , Yu Le , Noethen Markus , Yu Chunshui , Marquand Andre , Schumann Gunter 
Published: September 2022

AbstractThe majority of people worldwide live in cities, yet how urban living affects brain and mental illness is scarcely understood. Urban lives are exposed to a a wide array of environmental factors that may combine and interact to influence mental health. While individual factors of the urban environment have been investigated in isolation, to date no attempt has been made to model how the complex, real life exposure to living in the city relates to brain and mental illness, and how it is moderated by genetic factors. Using data of over 150,000 participants of the UK Biobank, we carried out sparse canonical correlation analyses (sCCA) to investigate the relation of urban living environment with symptoms of mental illness. We found three mental health symptom groups, consisting of affective, anxiety and emotional instability symptoms, respectively. These groups were correlated with distinct profiles of urban environments defined by risk factors related to social deprivation, air pollution and urban density, and protective factors involving green spaces and generous land use. The relations between environment and symptoms of mental illness were mediated by the volume of brain regions involved in reward processing, emotional processing and executive control, and moderated by genes regulating stress response, neurotransmission, neural development and differentiation, as well as epigenetic modifications. Together, these findings indicate distinct biological pathways by which different environmental profiles of urban living may influence mental illness. Our results also provide a quantitative measure of the contribution of each environmental factor to brain volume and symptom group. They will aid in targeting and prioritizing important decisions for planning and public health interventions.