bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis
Authors: Reygaerts Thomas , Laohamonthonkul Pawat , Hrovat-Schaale Katja , Moghaddas Fiona , Baker Paul J , Gray Paul E , Masters Seth L 
Published: July 2023

Abstract

Objective
The p.E148Q variant in pyrin is present in different populations at a frequency of up to 29%, and has been associated with diseases, including vasculitis and FMF. The pathogenicity of p.E148Q in FMF is unclear, even when observed in cis or in trans to a single, typically recessive, pathogenic mutation. We performed functional validation to determine whether p.E148Q increases the ability of pyrin to form an active inflammasome complex in cell lines.

Methods
We interrogated the Australian Autoinflammatory Disease RegistrY (AADRY) to find candidate inheritance patterns for the p.E148Q variant in pyrin. Different pyrin variant combinations were tested in HEK293T cells stably expressing the adaptor protein apoptosis-associated speck-like (ASC), which were analysed by flow cytometry to visualize inflammasome formation, with and without stimulation by Clostridioides difficile toxin B (TcdB). Inflammasome-dependent cytokine secretion was also quantified by ELISA of supernatants from THP-1 cells transduced with lentiviral expression vectors.

Results
In AADRY, we observed the p.E148Q allele in individuals with autoinflammatory diseases alone or in conjunction with other pyrin variants. Two FMF families harboured the allele p.E148Q-M694I in cis with dominant heritability. In vitro, p.E148Q pyrin could spontaneously potentiate inflammasome formation, with increased IL-1β and IL-18 secretion. p.E148Q in cis to classical FMF mutations provided significant potentiation of inflammasome formation.

Conclusion
The p.E148Q variant in pyrin potentiates inflammasome activation in vitro. In cis, this effect is additive to known pathogenic FMF mutations. In some families, this increased effect could explain why FMF segregates as an apparently dominant disease.
Taxonomy and molecular phylogenetic position of new species and new records of Coelosphaeridae (Demospongiae: Poecilosclerida) from the Mexican Pacific
Authors: Cruz-Barraza José Antonio , Carballo José Luis , Aguilar-Camacho José María 
Published: July 2023

Abstract
Poecilosclerida is the largest and the most diverse order in the class Demospongiae and one of the least studied in the tropical Pacific Ocean. In this study, two new species and two new faunistic records of Coelosphaeridae are described from the Mexican Pacific Ocean. Celtodoryx chichiltik sp. nov. and Lissodendoryx (Anomodoryx) incrustans sp. nov. also constitute the first records of the monotypic genus Celtodoryx and the subgenus Anomodoryx from the Eastern Pacific Region. In addition, the re-description of Lissodendoryx (Waldoschmittia) hawaiiana and Lissodendoryx (Lissodendoryx) albemarlensis with new regional records are included. The cytochrome c oxidase subunit I (COI) mtDNA and 28S rDNA (C1–D2 domains) were sequenced, and molecular phylogenetic analyses of the two loci revealed that Coelosphaeridae is not monophyletic. In the 28S tree topology, neither Lissodendoryx nor Celtodoryx are monophyletic, and sequences of the two genera are members of two distinct clades containing sequences of other Poecilosclerida species. 28S sequences of L. (W.) hawaiiana show high similarities between specimens from the Mexican Pacific and a specimen from Hawaii (type locality), suggesting a wide distribution range of this sponge species in the Pacific Ocean. COI topology shows that the majority of Lissodendoryx (including our sequences) were grouped within the same molecular clade.
Surgical Treatment of Congenital Muscular Torticollis: Significant Improvement in Health-related Quality of Life Among a 2-year Follow-up Cohort of Children, Adolescents, and Young Adults
Authors: Høiness Per Reidar , Medbøe Anja 
Published: July 2023

Objective:
Surgical treatment of congenital muscular torticollis (CMT) has been proven clinically effective in cases that fail to normalize after conservative treatment, but reports on self-reported outcome and quality of life have been scarce. This study aimed to assess health-related quality of life (HRQoL) in children, adolescents, and young adults undergoing surgical treatment for CMT, comparing HRQoL with clinical outcomes.

Methods:
We conducted a level 2 prospective observational study on a surgically treated CMT cohort at a single tertiary center. The surgeries focused on releasing all tightness, and the medial head was routinely elongated to preserve cosmetic function. Patients underwent rigorous pre/postoperative assessments and follow-up. A strict postoperative protocol entailing stretching, physiotherapy, and positional exercises was adhered to for a minimum of 6 months. The Cheng and Tang torticollis scoring system and PedsQLTM 4.0 generic core scales were used to evaluate clinical outcome and HRQoL, respectively.

Results:
The study included 31 patients, averaging 11.4 years. Significant improvements in range of motion, deformities, and overall subjective satisfaction were observed 2 years postoperatively. The Cheng and Tang score improved overall significantly from fair (9.9 points) to excellent (17.9 points) after 2 years (P<0.001). The oldest patients showed less improvement than the youngest ones, especially regarding craniofacial asymmetry (P=0.004). Patient PedsQL scores significantly improved 2 years post-surgery (P=0.040), with no discernable age differences.

Conclusion:
Our findings demonstrated significant improvements in both HRQoL and clinical outcomes after surgical treatment of CMT. The PedsQL score seemed sensitive to the clinical changes.
Efficacy of Varying Surgical Approaches on Achieving Optimal Alignment in Adult Spinal Deformity Surgery
Authors: Passias Peter G. , Ahmad Waleed , Williamson Tyler K. , Lebovic Jordan , Kebaish Khaled , Lafage Renaud , Lafage Virginie , Line Breton , Schoenfeld Andrew J. , Diebo Bassel G. , Klineberg Eric O. , Kim Han Jo , Ames Christopher P. , Daniels Alan H. , Smith Justin S. , Shaffrey Christopher I. , Burton Douglas C. , Hart Robert A. , Bess Shay , Schwab Frank J. , Gupta Munish C. ,   International Spine Study Group
Published: July 2023

Background:
The Roussouly, SRS-Schwab, and Global Alignment and Proportion (GAP) classifications define alignment by spinal shape and deformity severity. The efficacy of different surgical approaches and techniques to successfully achieve these goals is not well understood.

Purpose:
Identify the impact of surgical approach and/or technique on meeting complex realignment goals in adult spinal deformity (ASD) corrective surgery.

Study Design/Setting:
Retrospective study.

Materials and Methods:
Included patients with ASD fused to pelvis with 2-year data. Patients were categorized by: (1) Roussouly: matching current and theoretical spinal shapes, (2) improving in SRS-Schwab modifiers (0, +, ++), and (3) improving GAP proportionality by 2 years. Analysis of covariance and multivariable logistic regression analyses controlling for age, levels fused, baseline deformity, and 3-column osteotomy usage compared the effect of different surgical approaches, interbody, and osteotomy use on meeting realignment goals.

Results:
A total of 693 patients with ASD were included. By surgical approach, 65.7% were posterior-only and 34.3% underwent anterior-posterior approach with 76% receiving an osteotomy (21.8% 3-column osteotomy). By 2 years, 34% matched Roussouly, 58% improved in GAP, 45% in SRS-Schwab pelvic tilt (PT), 62% sagittal vertical axis, and 70% pelvic incidence-lumbar lordosis. Combined approaches were most effective for improvement in PT [odds ratio (OR): 1.7 (1.1–2.5)] and GAP [OR: 2.2 (1.5–3.2)]. Specifically, anterior lumbar interbody fusion (ALIF) below L3 demonstrated higher rates of improvement versus TLIFs in Roussouly [OR: 1.7 (1.1–2.5)] and GAP [OR: 1.9 (1.3–2.7)]. Patients undergoing pedicle subtraction osteotomy at L3 or L4 were more likely to improve in PT [OR: 2.0 (1.0–5.2)] and pelvic incidence-lumbar lordosis [OR: 3.8 (1.4–9.8)]. Clinically, patients undergoing the combined approach demonstrated higher rates of meeting SCB in Oswestry Disability Index by 2 years while minimizing rates of proximal junctional failure, most often with an ALIF at L5-S1 [Oswestry Disability Index-SCB: OR: 1.4 (1.1–2.0); proximal junctional failure: OR: 0.4 (0.2–0.8)].

Conclusions:
Among patients undergoing ASD realignment, optimal lumbar shape and proportion can be achieved more often with a combined approach. Although TLIFs, incorporating a 3-column osteotomy, at L3 and L4 can restore lordosis and normalize pelvic compensation, ALIFs at L5-S1 were most likely to achieve complex realignment goals with an added clinical benefit and mitigation of junctional failure.
Single-institution Series of Hirayama Disease in North America
Authors: Lynch Benjamin T. , Slingerland Anna L. , Robson Caroline D. , Ghosh Partha S. , Hedequist Daniel J. , Proctor Mark R. , Fehnel Katie P. 
Published: July 2023

Study Design:A retrospective chart review.Objective:The aims of this study were to review pathophysiology, workup, and treatment for Hirayama disease (HD); and to assess outcomes from a single institution.Summary of Background Data:HD is a rare, painless, cervical myelopathy with distal upper extremity weakness, muscle wasting, and spinal cord atrophy. Disease progression—a consequence of repeat flexion injury—occurs up to 5 years from the initial diagnosis.Methods:Single-institution review of pediatric HD patients from 2010 to 2020.Results:Patients (n=10 male, n=2 female) presented in the second decade (14–20 y) with painless progressive distal upper extremity weakness and atrophy without sensory loss. Electromyography (n=12) demonstrated denervation in C7–T1 myotomes and flexion/extension magnetic resonance imaging showed focal cord atrophy and anterior displacement of the posterior dura with epidural enhancement in flexion. Treatment included observation and external orthoses (n=9) and anterior cervical discectomy with fusion (n=3). One of the 9 patients managed conservatively experienced further deterioration; no patient who underwent anterior cervical discectomy with fusion progressed.Conclusions:Patients with HD require a multidisciplinary approach to diagnosis and treatment to preserve function. Treatment is preventive and aims to minimize flexion injury by inhibiting motion across involved joints. First-line management is avoidance of neck flexion and use of rigid orthosis; in cases of failed conservative management and/or rapid clinical deterioration, surgical fixation can be offered.
Human Beauty according to Artificial Intelligence
Authors: Kenig Nitzan , Monton Echeverria Javier , Muntaner Vives Aina 
Published: July 2023

Summary:
This work explores the upcoming era of artificial intelligence (AI), its potential impact on societal norms and aesthetics, and the biases inherent in AI systems. With the ability to generate realistic human-like art and language, AI entities like DALL·E or Midjourney have significant cultural and economic implications, particularly in creative sectors. However, our study highlights potential biases in AI, demonstrated through a text-to-image model called Craiyon, which was found to generate oversized and sexually suggestive images of breasts when prompted with certain phrases. These results underline the influence of societal norms on AI and the risk of perpetuating harmful stereotypes or unrealistic beauty standards. We emphasize the need for vigilance in monitoring AI’s learning processes and potential biases, particularly as AI starts playing a crucial role in shaping societal perceptions of beauty and self. More inclusive and diverse AI models are needed to better represent the complexity of human beauty and to avoid biases.
Thiopurines Maintenance Therapy in Children With Ulcerative Colitis: A Multicenter Retrospective Study
Authors: Abu Hanna Firas , Atia Ohad , Yerushalmy Feler Anat , Shouval Dror , Weiss Batia , Mresat Hadeel , Magen-Rimon Ramit , Zifman Eyal , Turner Dan , Rinawi Firas 
Published: July 2023

Background and Aims:
Thiopurines are an established treatment for pediatric ulcerative colitis (UC). However, data regarding safety and efficacy are lacking. We aimed to determine short and long-term outcome following thiopurines use in children with UC.

Methods:
We conducted a retrospective review of children (2–18 years) with UC treated with thiopurines between January 2008 and January 2019 at 7 medical centers in Israel. The primary outcome was corticosteroid (CS)-free clinical remission at week 52 following thiopurines initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy).

Results:
A total of 133 children were included [median age at diagnosis of 12.4 (interquartile range 11.0–15.8) years, 30 (23%) left-sided colitis, 113 (85%) with moderate or severe disease at diagnosis]. At diagnosis 58 patients (44%) were treated with 5-aminosalicylates and 72 (54%) with CS. Sixty patients (45%) received thiopurines as 1st line maintenance therapy. Seventy-four patients (56%) had CS-free clinical remission at week 52 without rescue therapy. Predictors of clinical remission were not identified. In a sub-analysis among patients with steroid-responsive moderate to severe UC, 59 (55%) patients achieved this outcome. The likelihood of remaining free of rescue therapy among thiopurines-treated patients was 83%, 62%, 45%, and 37% at 1, 2, 3, and 4 years, respectively.

Conclusion:
More than half of children with UC starting thiopurines without previous or concomitant biologic therapy have CS-free clinical remission at 52 weeks later without the need for rescue therapy. Thiopurines are effective in pediatric UC and could be considered prior to biologics.
Prolonged Survival Using Outpatient Palliative Chemotherapy in Two Children With Refractory Acute Myelogenous Leukemia
Authors: MacDonell-Yilmaz Rebecca E. , Sampino Emily Vistica , Moynihan Laura , Chang Wen-i , Sprinz Philippa G. 
Published: July 2023

Background:
Therapy options for relapsed/refractory acute myelogenous leukemia (AML) are limited. Palliative chemotherapy options have been explored in adult patients, but little evidence exists in children.

Objectives:
Describe the clinical course of 2 pediatric patients with refractory AML who transitioned to outpatient palliative chemotherapy with good disease control and quality of life on these regimens.

Patients and Methods:
Patient 1 was a 2-year-old girl who received a total of 4 cycles of standard chemotherapy with multiple complications and 15% to 20% blasts on marrow subsequent evaluation. An outpatient regimen of decitabine and vorinostat was consequently chosen for her. Patient 2 was a 16-year-old boy with residual disease after induction 1 with arm A with cytarabine, daunorubicin, and etoposide. His induction 2 course was complicated by multiorgan failure secondary to multiple infections including Klebsiella pneumonia and radiographically identified pulmonary fungal disease. On recovery, the marrow showed no disease but after the toxicities of initial therapy, the patient pursued a palliative regimen with azacitidine and lenalidomide.

Results:
Patient 1 tolerated her regimen for 14 months, requiring weekly blood products and only one hospitalization for a central-line infection. Her blast count then increased precipitously, the disease progressed, and she died comfortably while receiving hospital-based end-of-life care. Patient 2 tolerated 14 months of his regimen. On a surveillance marrow sample, he was found to have 0.02% minimal residual disease. He then elected to pursue marrow transplantation. He maintained remission until his 6-month posttransplant surveillance bone marrow biopsy, which revealed 0.04% minimal residual disease.

Conclusion:
We describe 2 pediatric patients with relapsed/refractory AML who achieved disease control and acceptable quality of life utilizing outpatient palliative chemotherapy for over 12 months. These regimens should be considered in patients who no longer desire cytotoxic chemotherapy or are ineligible for further aggressive approaches.
The Evolving Spectrum of Endometrial Glandular Proliferations With Corded and Hyalinized Features
Authors: Pors Jennifer , Weiel Julianna J. , Ryan Emily , Longacre Teri A. 
Published: July 2023

We present the clinicopathologic and immunohistochemical features of 14 endometrial glandular proliferations with conspicuous corded and hyalinized (CH) features comprised entirely or predominantly of endometrial hyperplasia. Endometrial glandular lesions ranged in severity from endometrial hyperplasia with and without cytologic atypia (5/14 [36%]) to hyperplasia with architectural complexity bordering on well-differentiated endometrioid adenocarcinoma (3/14 [21%]) to frank corded and hyalinized endometrial carcinoma (“CHEC”) (6/14 [43%]). In addition to sex cord–like growth and hyalinized stroma, other common histologic features included prominent spindle cells (11/14 [79%]), keratinizing and/or morular squamous differentiation (10/14 [71%]), and osseous metaplasia (6/14 [43%]). Immunohistochemical characterization revealed aberrant nuclear beta-catenin in all cases (14/14 [100%]); additionally, all cases demonstrated positive estrogen receptors, intact PTEN, PMS2 and MSH6, and wild-type p53 expression. Patients ranged in age from 24 to 58 (mean 38) years. Of 5 patients with hyperplasia with CH features, 2 experienced complete resolution after progestin therapy and none progressed to adenocarcinoma (mean follow-up 15.6 mo, range 2 to 64). By contrast, of 2 patients with hyperplasia bordering on CHEC and with available follow-up, both subsequently developed adenocarcinoma, suggesting that even focal increased architectural complexity may predict an elevated risk of malignancy. We conclude that CH morphology is not limited to endometrioid carcinoma and may occur across a spectrum of neoplastic proliferations, including those without sufficient architectural complexity or cytologic atypia to warrant classification as adenocarcinoma. We propose the term “corded and hyalinized endometrial hyperplasia” to describe this precursor lesion and report favorable outcomes with conservative treatment.
Evaluating the Long-term Impact of Implementing Standardized Postoperative Opioid Prescribing Recommendations Following Pelvic Organ Prolapse Surgery
Authors: Olive Elizabeth J. , Glasgow Amy E. , Habermann Elizabeth B. , Gebhart John B. , Occhino John A. , Trabuco Emanuel C. , Linder Brian J. 
Published: July 2023

Importance
Improving opioid stewardship is important, given the common use of opioids and resultant adverse events. Evidence-based prescribing recommendations for surgeons may help reduce opioid prescribing after specific procedures.

Objective
The aim of this study was to assess longitudinal prescribing patterns for patients undergoing pelvic organ prolapse surgery in the 2 years before and after implementing evidence-based opioid prescribing recommendations.

Study Design
In December 2017, a 3-tiered opioid prescribing recommendation was created based on prospective data on postoperative opioid use after pelvic organ prolapse surgery. For this follow-up study, prescribing patterns, including quantity of opioids prescribed (in oral morphine equivalents [OMEs]) and refill rates, were retrospectively compared for patients undergoing prolapse surgery before (November 2015–November 2017; n = 238) and after (December 2017–December 2019; n = 361) recommendation implementation. Univariate analysis was performed using the Wilcoxon rank sum and χ
2 tests. Cochran-Armitage trend tests and interrupted time-series analysis tested for significance in the change in OMEs prescribed before versus after recommendation implementation.

Results
After recommendation implementation, the quantity of postoperative opioids prescribed decreased from median 225 mg OME (interquartile range, 225, 300 mg OME) to 71.3 mg OME (interquartile range, 0, 112.5 mg OME; P < 0.0001). Decreases also occurred within each subgroup of prolapse surgery: native tissue vaginal repair (P < 0.0001), robotic sacrocolpopexy (P < 0.0001), open sacrocolpopexy (P < 0.0001), and colpocleisis (P < 0.003). The proportion of patients discharged following prolapse surgery without opioids increased (4.2% vs 36.6%; P < 0.0001), and the rate of opioid refills increased (2.1% vs 6.0%; P = 0.02).

Conclusions
With 2 years of postimplementation follow-up, the use of procedure-specific, tiered opioid prescribing recommendations at our institution was associated with a significant, sustained reduction in opioids prescribed. This study further supports using evidence-based recommendations for opioid prescribing.
The Impact of Vaginal Probiotics on Pessary Use: A Randomized Controlled Trial
Authors: Sappenfield Elisabeth C. , Mellen Colleen , Wilcox Jennifer , O'Hanlon Deirdre Elizabeth , O'Sullivan David M. , Tunitsky-Bitton Elena 
Published: July 2023

Importance
Pessary-related adverse effects are common, and treatment options are limited. Probiotics may improve pessary-related adverse effects by altering the vaginal microenvironment.

Objective
This study aimed to evaluate the effect of a vaginal probiotic suppository on the vaginal microenvironment among pessary users.

Study Design
Women who used pessaries were randomized to vaginal probiotic suppository use versus without use. The intervention was a vaginal probiotic suppository and moisturizing vaginal gel. The vaginal microenvironment was assessed using Gram stain and Nugent's criteria at baseline and 3 months by a microbiologist blinded to group allocation. Symptoms and experience with use of the probiotic were assessed using questionnaires. The primary outcome was change in lactobacilli count on Nugent subscore at 3 months.

Results
A total of 147 postmenopausal women were randomized (86 to the intervention arm and 61 to the control arm), and 124 (87.9%) presented for a 3-month follow-up. There was no difference between the arms in age, race, body mass index, and Charlson Comorbidity Index. A majority of participants had the pessary managed by the health care professional (intervention arm vs control arm, 46 [76.7%] vs 55 [68.8%]; P = 0.30). Composition of the vaginal microenvironment did not differ with or without probiotic treatment at 3 months. Bother from vaginal symptoms, including discharge, itching, and discomfort, did not differ between arms. Adverse effects from the intervention were minor, resolved with discontinuation, and occurred at 39.1%.

Conclusion
Vaginal probiotic suppository use did not affect the composition of the vaginal microenvironment, patient satisfaction, or vaginal symptoms after 3 months of use in pessary users.