bluuebunny/crossref_metadata_2025_split huggingface dataset:
TFIIS is required for reproductive development and thermal adaptation in barley
Authors: Ahmad Imtiaz , Kis András , Verma Radhika , Szádeczky-Kardoss István , Szaker Henrik Mihály , Pettkó-Szandtner Aladár , Silhavy Dániel , Havelda Zoltán , Csorba Tibor 
Published: October 2024

Abstract
Key message
Barley reproductive fitness and efficient heat stress adaptation requires the activity of TFIIS, the elongation cofactor of RNAPII.

Abstract
Regulation of transcriptional machinery and its adaptive role under different stress conditions are studied extensively in the dicot model plant Arabidopsis, but our knowledge on monocot species remains elusive. TFIIS is an RNA polymerase II-associated transcription elongation cofactor. Previously, it was shown that TFIIS ensures efficient transcription elongation that is necessary for heat stress survival in A. thaliana. However, the function of TFIIS has not been analysed in monocots. In the present work, we have generated and studied independent tfIIs-crispr-mutant barley lines. We show that TFIIS is needed for reproductive development and heat stress survival in barley. The molecular basis of HS-sensitivity of tfIIs mutants is the retarded expression of heat stress protein transcripts, which leads to late accumulation of HSP chaperones, enhanced proteotoxicity and ultimately to lethality. We also show that TFIIS is transcriptionally regulated in response to heat, supporting a conserved adaptive function of these control elements for plant thermal adaptation. In sum, our results are a step forward for the better understanding of transcriptional machinery regulation in monocot crops.
Computed tomography referral guidelines adherence in Europe: insights from a seven-country audit
Authors: Singer Clara , Saban Mor , Luxenburg Osnat , Yellin Lucia Bergovoy , Hierath Monika , Sosna Jacob , Karoussou-Schreiner Alexandra , Brkljačić Boris 
Published: October 2024

Abstract

Background
Ensuring appropriate computed tomography (CT) utilization optimizes patient care while minimizing radiation exposure. Decision support tools show promise for standardizing appropriateness.

Objectives
In the current study, we aimed to assess CT appropriateness rates using the European Society of Radiology (ESR) iGuide criteria across seven European countries. Additional objectives were to identify factors associated with appropriateness variability and examine recommended alternative exams.

Methods
As part of the European Commission-funded EU-JUST-CT project, 6734 anonymized CT referrals were audited across 125 centers in Belgium, Denmark, Estonia, Finland, Greece, Hungary, and Slovenia. In each country, two blinded radiologists independently scored each exam’s appropriateness using the ESR iGuide and noted any recommended alternatives based on presented indications. Arbitration was used in case auditors disagreed. Associations between appropriateness rate and institution type, patient’s age and sex, inpatient/outpatient patient status, anatomical area, and referring physician’s specialty were statistically examined within each country.

Results
The average appropriateness rate was 75%, ranging from 58% in Greece to 86% in Denmark. Higher rates were associated with public hospitals, inpatient settings, and referrals from specialists. Variability in appropriateness existed by country and anatomical area, patient age, and gender. Common alternative exam recommendations included magnetic resonance imaging, X-ray, and ultrasound.

Conclusion
This multi-country evaluation found that even when using a standardized imaging guideline, significant variations in CT appropriateness persist, ranging from 58% to 86% across the participating countries. The study provided valuable insights into real-world utilization patterns and identified opportunities to optimize practices and reduce clinical and demographic disparities in CT use.

Key Points

Question

Largest multinational study (7 EU countries, 6734 CT referrals) assessed real-world CT appropriateness using ESR iGuide, enabling cross-system comparisons.

Findings

Significant variability in appropriateness rates across institution type, patient status, age, gender, exam area, and physician specialty, highlighted the opportunities to optimize practices based on local factors.

Clinical relevance

International collaboration on imaging guidelines and decision support can maximize CT benefits while optimizing radiation exposure; ongoing research is crucial for refining evidence-based guidelines globally.
ESR Essentials: role of PET/CT in neuroendocrine tumors—practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging
Authors: Ebner Ricarda , Sheikh Gabriel T. , Brendel Matthias , Ricke Jens , Cyran Clemens C. 
Published: October 2024

Abstract
Neuroendocrine neoplasms (NEN) originate from the secretory cells of the neuroendocrine system, with the majority arising in the gastrointestinal tract and pancreas. Given the heterogeneity in the biological behavior and morphological differentiation of these tumors, advanced imaging techniques are crucial for supporting the suspected diagnosis, accurate staging, and monitoring therapy. As most well-differentiated NEN demonstrate overexpression of somatostatin receptors (SSR) on the cell surface, SSR-directed PET/CT is considered the reference standard for imaging of this particular entity. SSR-PET/CT should be the imaging method of choice in every NEN G1 or G2 and considered for re-staging after both potentially curative and non-curative surgeries. The extent of SSR expression is also crucial for determining a patient’s eligibility for peptide receptor radionuclide therapy (PRRT). PRRT utilizes [177Lu]Lu-DOTA-TATE to target the SSR receptor and can significantly prolong progression-free survival in patients with advanced, progressive neuroendocrine tumor of the gastroenteropancreatic system (GEP-NET). PET/CT is a central component of the multidisciplinary management of NEN. Variable follow-up intervals are recommended, considering that tumors with higher proliferation rates or advanced metastatic disease require more frequent assessments. The combination with other imaging modalities, like MRI, complements SSR-PET/CT, further enhancing overall diagnostic accuracy.

Key Points

Somatostatin receptor-PET/CT (SSR-PET/CT) is the guideline-recommended reference standard for imaging well-differentiated neuroendocrine tumors (NET).

SSR-PET/CT should be the diagnostic imaging of choice for staging and post-therapy re-staging of grade 1 or 2 NET (G1 or G2).

Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.
Differential fatty acids utilization across life stages in a Vespa species
Authors: Bouchebti Sofia , Levin Eran 
Published: October 2024

Abstract
Dietary fatty acids (FAs) are essential macronutrients affecting animal fitness, growth, and development. While the degree of saturation of FAs usually determines the level of absorption and allocation within the body, the utilization of dietary FAs across the life stages of individuals remains unknown. We used three different 13 C labeled FAs, with a different saturation level (linoleic acid (18:2), oleic acid (18:1), and palmitic acid (16:0)), to investigate the absorption and allocation of dietary FAs across the life stages of the Oriental hornet. Our results show that only larvae utilized all tested FAs as metabolic fuel, with palmitic acid being oxidized at the highest rate. Oleic and palmitic acids were predominantly incorporated into larval tissues, while oleic acid dominated pupal tissues. In contrast, linoleic and oleic acids were predominantly incorporated into adult tissues. These findings highlight a life stage-dependent shift in certain FAs utilization, with palmitic acid mostly utilized in early stages and linoleic acid in adulthood, while oleic acid remained consistently utilized across all life stages. This study emphasizes the importance of considering FA saturation and life stage dynamics in understanding FA utilization patterns.
Effect of postpartum pessary use on pelvic floor function: a prospective multicenter study
Authors: Beer Franziska , Kuppinger Madeleine , Schwab Frank , Hübner Markus , Kiefner Brenda , Nacke Anna , Kelkenberg Ute , Schütze Sabine , Lindner Anna , Hellmeyer Lars , Janni Wolfgang , Metz Melanie , Deniz Miriam 
Published: October 2024

Abstract
Purpose
This study evaluates the restitution of pelvic floor function in postpartum women using the Restifem® pessary in a preventive and therapeutic approach.

Methods
In this multicentre study all postpartum women independently of their parity, mode of delivery and existing pelvic floor symptoms were offered to use the Restifem® pessary from 6 weeks postpartum for 3 to 6 months. They completed the validated German pelvic floor questionnaire (GPFQpp) via online survey at 6 weeks, 6 months and 12 months postpartum and were divided, by their own choice, into users and non-users of the pessary.

Results
Initially 857 women were enrolled. After 6 weeks 137 pessary users and 133 non-users, after 12 months 53 pessary users and 45 non-users submitted a completed questionnaire. Pessary users had significantly higher (worse) scores in all domains of the GPFQpp at 6 weeks postpartum. At 12 months postpartum pessary users still had a significantly higher bladder score, compared to non-users. There was a greater improvement in the bladder score (p = 0.005) and the pelvic organ prolapse score (p < 0.001) from 6 weeks to 12 months postpartum, among pessary users compared to non-users.

Conclusion
Pessary users had a significantly greater improvement in pelvic floor function from 6 weeks to 12 months postpartum, compared to non-users. This effect might be in part due to wearing the pessary but also due to greater scope for recovery, given the higher level of pelvic floor dysfunction in the pessary user group.

Trial registration.
The trial was registered in the German Clinical Trials Register (DRKS00024733) on 19 of April 2021.
S100 and CD34 positive spindle cell tumors of the uterine cervix with EGFR mutation: a hitherto unrecognized neoplasm phenotypically and epigenetically overlapping with “NTRK-rearranged spindle cell neoplasms” of the uterus
Authors: Michal Michael , Kuruc Josef , Hájková Veronika , Michalová Květoslava , Klubíčková Natálie 
Published: October 2024

AbstractNTRK-rearranged spindle cell neoplasm represents an emerging entity included in the latest 5th edition of WHO classification of both soft tissue and female genital tumors. By immunohistochemistry, they are commonly positive for CD34, S100 protein, and CD30 and typically harbor fusions of kinase genes such as NTRK1/2/3, RET, and BRAF. In the gynecological tract, they typically affect the uterine cervix or uterine body. Most of the reported cases had fibrosarcoma-like morphology, occasionally showing perivascular and stromal hyalinization with only a few cases showing a less cellular spindle cell proliferation. Except for one case with RET fusion, all other gynecological cases harbored exclusively NTRK1/2/3 fusions. Besides kinase gene fusions, the analogous tumors in soft tissues may also harbor activating EGFR or BRAF point mutations, but no such case has been described in the uterus. Herein we are reporting two cases from the uterine cervix showing morphology and molecular features previously unreported at this anatomic site. The patients were 46 and 34 years old and clinically presented with unremarkable cervical polyps each measuring 8 mm in diameter. Histologically, both cases had a rounded polypoid outline and were composed of hypocellular proliferation of bland spindle cells lacking mitotic activity and growing in a fibrotic stroma which was punctuated by prominent small vessels with thick hyalinized walls. Immunohistochemically, both showed a diffuse expression of CD34, CD30, and S100 protein, whereas SOX10 was negative. Both cases harbored exon 20 EGFR mutation and did not reveal any fusions or significant copy number changes. The patient in case 1 was treated by hysterectomy with salpingectomy with no other residual tumor detected, and she was alive and well 27 months after the diagnosis. The patient in case 2 had no other known tumors at the time of diagnosis, but no follow-up is available. We believe the reported cases represent a hitherto unrecognized variant of “NTRK-rearranged spindle cell neoplasms” of the uterine cervix with novel EGFR mutations.
FGFR3::TACC3 fusions in head and neck carcinomas: a study of nine cases highlighting phenotypic heterogeneity, frequent HPV association, and a morphologically distinct subset in favor of a putative entity
Authors: Agaimy Abbas , Antonescu Cristina R. , Bell Diana , Breimer Gerben E. , Dermawan Josephine K. , Kester Lennart A. , Laco Jan , Rijken Johannes A. , Whaley Rumeal D. , Stoehr Robert , Cramer Thomas , Bishop Justin A. 
Published: October 2024

AbstractThe FGFR3::TACC3 fusion has been reported in subsets of diverse cancers including urothelial and squamous cell carcinomas (SCC). However, the morphology of FGFR3::TACC3-positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine FGFR3::TACC3 fusion–positive head and neck carcinomas affecting six males and three females aged 38 to 89 years (median, 59). The tumors originated in the sinonasal tract (n = 4), parotid gland (n = 2), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9–21 months; median, 11), four patients developed local recurrence and/or distant metastases, two died of disease at 11 and 12 months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or DEK::AFF2 carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame FGFR3::TACC3 fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring FGFR3::TACC3 fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.
Psychometric properties of the preschool strengths and difficulties questionnaire (SDQ) in UK 1-to-2-year-olds
Authors: Byrne Elizabeth M. , Eneberi Annette , Barker Beth , Grimas Ellen , Iles Jane , Pote Helen , Ramchandani Paul G. , O’Farrelly Christine M. 
Published: October 2024

AbstractEarly identification of emotional and behavioural difficulties in very young children is crucial for intervention and prevention. The Strengths and Difficulties Questionnaire (SDQ) is a widely used measure of child and adolescent mental health that is brief, cost-effective, and easy to administer. The aims of this study were to establish the validity and reliability of the preschool SDQ in UK 1-2-year-olds. This study investigated the psychometric properties of the Preschool SDQ in a large UK sample (N = 2040; female = 46.86%; male = 50.83%, sex not recorded = 2.30%) of infants and toddlers (1-2-year-olds). Analyses were performed at item-level (internal consistency, internal structure, measurement invariance) and scale-level (test–retest reliability, convergent validity). Similar to previous research, confirmatory factor analysis supported a slightly modified five-factor model, including the addition of a positive construal method factor, resulting in satisfactory data fit and a moderately good fitting model. Internal consistency (Cronbach’s alpha) for the SDQ total difficulties score was satisfactory, and higher for externalising over internalising problems. Moderate to strong correlations indicated good test–retest reliability, and moderate correlations indicated convergent validity between the SDQ and Child Behavior Checklist (CBCL), but associations were weaker than those found in studies with older children. Conclusions: The SDQ demonstrated satisfactory psychometric properties, suggesting that it may be a useful tool for the detection of early mental health difficulties, particularly externalising symptoms, even in very young toddlers. Further research is needed to validate the SDQ in younger populations and to establish cut-off scores for clinical interpretation. The implications of these findings are discussed.

What is known:• Clinically significant emotional and behavioural problems can and do emerge in early toddlerhood.• Parenting interventions can reduce mental health problems.• Valid, reliable, brief, and affordable tools are needed to identify very young children who may benefit from such support.What is new:• The Strengths and Difficulties Questionnaire was found to have acceptable factor structure and psychometric properties for use with young children aged 1-2 years old in the UK.• The externalising subscale in particular shows promise as an early screening tool.
Palpable signs of skull fractures on physical examination and depressed skull fractures or traumatic brain injuries on CT in children
Authors: Bressan Silvia , Tancredi Daniel , Casper Charles T. , Da Dalt Liviana , Kuppermann Nathan 
Published: October 2024

AbstractTo assess the actual presence of underlying depressed skull fractures and traumatic brain injuries (TBI) on computed tomography (CT) in children with and without palpable skull fractures on physical examination following minor head trauma. This was a secondary analysis of a prospective, observational multicenter study enrolling 42,412 children < 18 years old with Glasgow Coma Scale scores ≥ 14 following blunt head trauma. A palpable skull fracture was defined per the treating clinician documentation on the case report form. Skull fractures and TBIs were determined on CT scan by site radiologists. Palpable skull fractures were reported in 368/10,698 (3.4%) children < 2 years old, and in 676/31,613 (2.1%) of older children. Depressed skull fractures on CT were observed in 56/273 (20.5%) of younger children with palpable skull fractures and in 34/3047 (1.1%) of those without (rate difference 19.4%; 95%CI 14.6–24.2%), and in 30/486 (6.2%) vs 63/11,130 (0.6%) of older children (rate difference 5.6%; 95%CI 3.5–7.8%). TBIs on CT were found in 73/273 (26.7%) and 189/3047 (6.2%) of younger children with and without palpable skull fractures (rate difference 20.5%; 95%CI 15.2–25.9), and in 61/486 (12.6%) vs 424/11,130 (3.8%) of older children (rate difference 8.7%; 95%CI 6.1–12.0).Conclusions: Although depressed skull fractures and TBIs on CT are more common in children with palpable fractures than those without, most of these children do not have underlying depressed fractures. The discriminatory ability of the scalp examination could be enhanced by direct bedside visualization of the skull, such as through ultrasound.

What is Known:

• “Palpable skull fractures” are a high-risk predictor in the PECARN traumatic brain injury (TBI) rule for children younger than 2 years.

• The reliability of physical exam findings suggestive of underlying skull fractures is unclear.

What is New:

• In children younger than 2 years of age, approximately one in five of those with “palpable skull fractures” will actually have a depressed skull fracture on CT, while 60% will have any skull fracture.

• The discriminatory ability of the scalp examination could be enhanced by direct bedside visualization of the skull, such as through ultrasound.
Splanchnic and cerebral oxygenation during cyclic phototherapy in preterm infants with hyperbilirubinemia
Authors: Dani Carlo , Remaschi Giulia , Rossi Federica , Fusco Monica , Poggi Chiara , Corsini Iuri , Pratesi Simone 
Published: October 2024

Abstract
Cyclic phototherapy (cPT) can achieve a reduction in total serum bilirubin comparable to that achieved with standard continuous PT in preterm infants. Our aim was to assess the effect of cPT on splanchnic (rSO2S) and cerebral (rSO2C) oxygenation measured by near-infrared spectroscopy (NIRS). We prospectively studied 16 infants with a gestational age of 25–34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebro-splanchnic oxygenation ratio (CSOR) were recorded before, during, and after cPT discontinuation. We found that rSO2S, FOES, and CSOR did not change during the study period. The overall duration of single or multiple courses of PT was 6.5 (6.0–13.5) h, but by cycling PT, the actual exposure was 3.0 (1.5–4.9) h. Twelve patients (75%) required 15 min/h cPT, and four (25%) required prolonging cPT to 30 min/h. None of the patients developed enteral feeding intolerance.
Conclusions: cPT treatment of hyperbilirubinemia in preterm infants does not affect splanchnic oxygenation or intestinal oxygen blood extraction, likely due to the short exposure to PT light, and it could contribute to decreasing the risk of feeding intolerance.

What is Known:• The assumption that phototherapy (PT) is innocuous with no serious adverse effects has been questioned.• Cyclic phototherapy (cPT) can achieve a reduction in total serum bilirubin comparable to that achieved with standard continuous PT in preterm infants.

What is New:• Splanchnic and cerebral oxygenation measured by near-infrared spectroscopy did not change during KMC.• cPT can contribute to decrease the risk of feeding intolerance likely due to the short exposure to PT light.
The role of institutional ethics committees in Austria
Authors: Schober Sophie , Klee Sascha , Trautinger Franz 
Published: October 2024

SummaryResearch involving human subjects or identifiable human material and data must be assessed by an ethics committee. The Karl Landsteiner University of Health Sciences has established a Commission on Ethics and Scientific Integrity to evaluate medical research conducted by its faculty and students and at its affiliated hospitals.All projects submitted to the Commission on Ethics and Scientific Integrity between 2018 and 2023 were analyzed regarding their major characteristics, the duration of the evaluation process, and votes issued.A total of 520 applications were electronically submitted during the observation period. Most of the studies were retrospective data analyses in the field of oncology, psychology and surgery. Most studies included less than 100 volunteers. Of the applications 50% received a final vote within 5 months, during which several revision rounds took place. Overall, about 77% of votes issued during the observation period were positive and 2% were rejections. In 11% files were closed due to withdrawal. In 11% final votes were pending at the end of the observation period due to requests for revisions.Our results emphasize the importance of institutional ethics committees using the example of the Commission on Ethics and Scientific Integrity at the Karl Landsteiner University. Such committees fill a gap in evaluating research not covered by Austrian legal regulations. Continuous development of standards, operating procedures, and national and international collaborations are required to assess and minimize risks to trial subjects and to provide a safe and productive environment for research in human medicine and related fields.