bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world Effectiveness and Safety of Risankizumab in Patients with Moderate to Severe Multirefractory Crohn’s Disease: A Belgian Multicentric Cohort Study
Authors: Alsoud Dahham , Sabino João , Franchimont Denis , Cremer Anneline , Busschaert Julie , D’Heygere François , Bossuyt Peter , Vijverman Anne , Vermeire Séverine , Ferrante Marc 
Published: January 2024

Abstract

Background
As real-world data on risankizumab in patients with moderate to severe Crohn’s disease (CD) are scarce, we evaluated its effectiveness and safety in multirefractory Belgian patients.

Methods
Data from consecutive adult CD patients who started risankizumab before April 2023 were retrospectively collected at 6 Belgian centers. Clinical remission and response were defined using the 2-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score with ≥50%. Both effectiveness end points were evaluated at week 24 and/or 52, while surgery-free survival and safety were assessed throughout follow-up.

Results
A total of 69 patients (56.5% female, median age 37.2 years, 85.5% exposed to ≥4 different advanced therapies and 98.6% to ustekinumab, 14 with an ostomy) were included. At week 24, 61.8% (34 of 55) and 18.2% (10 of 55) of patients without an ostomy achieved steroid-free clinical response and remission, respectively. At week 52, these numbers were 58.2% (32 of 55) and 27.3% (15 of 55), respectively. Endoscopic data were available in 32 patients, of whom 50.0% (16 of 32) reached endoscopic response within the first 52 weeks. Results in patients with an ostomy were similar (steroid-free clinical response and remission, 42.9% and 14.3%, respectively). During a median follow-up of 68.3 weeks, 18.8% (13 of 69) of patients discontinued risankizumab, and 20.3% (14 of 69) of patients underwent CD-related intestinal resections. The estimated surgery-free survival at week 52 was 75.2%. No new safety issues were observed.

Conclusions
In this real-world cohort of multirefractory CD patients, risankizumab was effective in inducing both clinical remission and endoscopic response. Risankizumab was well tolerated with no safety issues.
Impact of age on pneumococcal colonization of the nasopharynx and oral cavity: an ecological perspective
Authors: Miellet Willem R , Mariman Rob , van Veldhuizen Janieke , Badoux Paul , Wijmenga-Monsuur Alienke J , Litt David , Bosch Thijs , Miller Elizabeth , Fry Norman K , van Houten Marianne A , Rots Nynke Y , Sanders Elisabeth A M , Trzciński Krzysztof 
Published: January 2024

Abstract
Pneumococcal carriage studies have suggested that pneumococcal colonization in adults is largely limited to the oral cavity and oropharynx. In this study, we used total abundance-based β-diversity (dissimilarity) and β-diversity components to characterize age-related differences in pneumococcal serotype composition of respiratory samples. quantitative PCR (qPCR) was applied to detect pneumococcal serotypes in nasopharyngeal samples collected from 946 toddlers and 602 adults, saliva samples collected from a subset of 653 toddlers, and saliva and oropharyngeal samples collected from a subset of 318 adults. Bacterial culture rates from nasopharyngeal samples were used to characterize age-related differences in rates of colonizing bacteria.
Dissimilarity in pneumococcal serotype composition was low among saliva and nasopharyngeal samples from children. In contrast, respiratory samples from adults exhibited high serotype dissimilarity, which predominantly consisted of abundance gradients and was associated with reduced nasopharyngeal colonization. Age-related serotype dissimilarity was high among nasopharyngeal samples and relatively low for saliva samples.
Reduced nasopharyngeal colonization by pneumococcal serotypes coincided with significantly reduced Moraxella catarrhalis and Haemophilus influenzae and increased Staphylococcus aureus nasopharyngeal colonization rates among adults.
Findings from this study suggest that within-host environmental conditions, utilized in the upper airways by pneumococcus and other bacteria, undergo age-related changes. It may result in a host-driven ecological succession of bacterial species colonizing the nasopharynx and lead to competitive exclusion of pneumococcus from the nasopharynx but not from the oral habitat. This explains the poor performance of nasopharyngeal samples for pneumococcal carriage among adults and indicates that in adults saliva more accurately represents the epidemiology of pneumococcal carriage than nasopharyngeal samples.
Contradictions and tensions in the way the USMCA regulates energy
Authors: Garcia Sanchez Guillermo J 
Published: January 2024

Abstract
The international regulation of energy is complex, involving various legal frameworks such as economic agreements, environmental conventions, and dispute resolution mechanisms. These instruments often overlap and may not align, creating challenges for addressing energy-related issues. The United States–Mexico–Canada Agreement (USMCA) exemplifies these complexities. It addresses entitlements to natural resources, protection of energy-related transactions, cross-border energy policies, and environmental externalities. However, the USMCA does not fully resolve conflicts among differing policy goals within the energy sector. This article examines how the USMCA navigates issues related to resource entitlements, energy transactions, policy clashes, and environmental concerns. It argues that the absence of a unified energy policy leaves disputes to be balanced by resolution bodies, such as arbitration panels. The article scrutinizes each aspect of the USMCA’s approach and discusses potential mechanisms for resolving policy conflicts. The USMCA’s treatment of energy-related matters underscores the intricate interplay between international economic law and the energy sector, with implications for regional competitiveness and sustainability.
An encoding of abstract dialectical frameworks into higher-order logic
Authors: Martina Antoine , Steen Alexander 
Published: January 2024

Abstract
An approach for encoding abstract dialectical frameworks and their semantics into classical higher-order logic is presented. Important properties and semantic relationships are formally encoded and proven using the proof assistant Isabelle/HOL. This approach allows for the computer-assisted analysis of abstract dialectical frameworks using automated and interactive reasoning tools within a uniform logic environment. Exemplary applications include the formal analysis and verification of meta-theoretical properties, and the generation of interpretations and extensions under specific semantic constraints.
Punctuated evolution of bill morphology in the largest family of songbirds (Thraupidae)
Authors: Vinciguerra Nicholas T , McCullough Jenna M , Burns Kevin J 
Published: January 2024

Abstract
We assessed correlations between speciation rate and bill morphology in an ecologically diverse and continental-scale songbird radiation, the tanagers (Thraupidae). Our analyses showed that bill size, shape, and their evolutionary rates are not correlated with speciation rate. However, we did find evidence that each axis of variation in bill morphology diversifies at speciation events interspersed with periods of gradual evolution, consistent with a punctuated equilibrium model of character change. To determine correlations, we incorporated a time-calibrated molecular phylogeny and high-resolution three-dimensional surface scans of bill structure from museum study skins. Overall, our findings suggest that bill size and shape diversify in association with the speciation process, but not through any effect on the rate of speciation. Previous studies have shown other traits, such as song, ecological niche, and plumage do influence speciation and, ultimately, species richness in tanagers.
A mechanistic biomarker investigation of fialuridine hepatotoxicity using the chimeric TK-NOG Hu-liver mouse model and in vitro micropatterned hepatocyte cocultures
Authors: Aslamkhan Amy G , Michna Laura , Podtelezhnikov Alexei , Vlasakova Katerina , Suemizu Hiroshi , Ohnishi Yasuyuki , Liu Liping , Lane Pamela , Xu Qiuwei , Kuhls Matthew C , Wang Zhibin , Pacchione Stephen , Erdos Zoltan , Tracy Rodger William , Koeplinger Kenneth , Muniappa Nagaraja , Valentine John , Galijatovic-Idrizbegovic Alema , Glaab Warren E , Sistare Frank D , Lebron Jose 
Published: January 2024

Abstract
Fialuridine (FIAU) is a nucleoside-based drug that caused liver failure and deaths in a human clinical trial that were not predicted by nonclinical safety studies. A recent report concluded that a TK-NOG humanized liver (hu-liver) mouse model detected human-specific FIAU liver toxicity, and broader use of that model could improve drug safety testing. We further evaluated this model at similar dose levels to assess FIAU sensitivity and potential mechanistic biomarkers. Although we were unable to reproduce the marked acute liver toxicity with two separate studies (including one with a “sensitized” donor), we identified molecular biomarkers reflecting the early stages of FIAU mitochondrial toxicity, which were not seen with its stereoisomer (FIRU). Dose dependent FIAU-induced changes in hu-liver mice included more pronounced reductions in mitochondrial to nuclear DNA (mtDNA/nucDNA) ratios in human hepatocytes compared to mouse hepatocytes and kidneys of the same animals. FIAU treatment also triggered a p53 transcriptional response and opposing changes in transcripts of nuclear- and mitochondrial-encoded mitochondrial proteins. The time dependent accumulation of FIAU into mtDNA is consistent with the ≥9-week latency of liver toxicity observed for FIAU in the clinic. Similar changes were observed in an in vitro micro-patterned hepatocyte coculture system. In addition, FIAU-dependent mtDNA/nucDNA ratio and transcriptional alterations, especially reductions in mitochondrially encoded transcripts, were seen in livers of non-engrafted TK-NOG and CD-1 mice dosed for a shorter period.
Conclusion: These mechanistic biomarker findings can be leveraged in an in vitro model and in a more routine preclinical model (CD-1 mice) to identify nucleosides with such a FIAU-like mitochondrial toxicity mechanistic liability potential. Further optimization of the TK-NOG hu-liver mouse model is necessary before broader adoption for drug safety testing.
Novel Calcium Phosphate Promotes Interbody Bony Fusion in a Porcine Anterior Cervical Discectomy and Fusion Model
Authors: Östman Maria , Försth Peter , Hedenqvist Patricia , Engqvist Håkan , Marcelino Leticia , Ytrehus Bjørnar , Hulsart-Billström Gry , Pujari-Palmer Michael , Öhman-Mägi Caroline , Höglund Odd , Forterre Franck 
Published: January 2024

Study Design.
Experimental porcine anterior cervical discectomy and fusion (ACDF) model: a proof-of-concept study.

Objective.
The effect of monetite synthetic bone graft (SBG) containing calcium pyrophosphate and β-tricalcium phosphate on cervical spinal fusion in a noninstrumented two-level large animal model.

Summary of Background Data.
ACDF is the gold standard surgical technique for the treatment of degenerative cervical spinal diseases. However, pseudarthrosis associated with increased patient morbidity occurs in ∼2.6% of the surgeries. SBG may enhance bony fusion and subsequently decrease the risk of pseudarthrosis. Recent studies on monetite-based SBGs for use in large cranial defects in humans have shown promising bone healing results, necessitating further investigation of their use in cervical spinal fusion.

Materials and Methods.
Four adult female Danish Göttingen minipigs received partial cervical anterior discectomy and intervertebral defects at an upper and lower level. One defect was filled with SBG, and the other was left empty. Bony fusion was evaluated using computed tomography (CT) at three-month intervals for 12 months. Fifteen months postsurgery, the animals were euthanized for further ex vivo qualitative histopathologic and micro-CT evaluations. Fusion rates were compared using the Fisher exact test at each time point.

Results.
Increased interbody bony fusion rates were observed at SBG levels (4/4) compared with control levels (0/4) evaluated by CT at 6 and 9 months postsurgery (P=0.029). Fusion was observed at all SBG levels 12 months postsurgery and at only one control level. Histopathologic evaluation confirmed high-quality interbody bony fusion at all SBG levels and fusion by spondylosis at one control level.

Conclusion.
This proof-of-concept study provides preliminary evidence of a novel, calcium pyrophosphate-containing, and β-tricalcium phosphate-containing monetite SBG that promotes bony fusion compared with a negative control in a clinically relevant porcine model of ACDF.
Effects of Minimally Invasive Lateral Lumbar Interbody Fusion with Accessory Rod Technique on Rod Fracture in Adult Spinal Deformity Surgery
Authors: Lee Ki Young , Lee Jung-Hee , Kang Kyung-Chung , Jung Cheol Hyun 
Published: January 2024

Study Design.
A retrospective study.

Objectives.
To analyze factors associated with rod fracture (RF) in adult spinal deformity (ASD), and to assess whether the accessory rod (AR) technique can reduce RF occurrence in deformity correction in the setting of minimally invasive lateral lumbar interbody fusion (LLIF).

Summary of Background Data.
Instrumentation failure is the most common reason for revision surgery in ASD. Several RF reduction methods have been introduced. However, there are insufficient studies on postoperative RF after deformity correction using minimally invasive LLIF.

Materials and Methods.
This study included 239 patients (average age 71.4 y and a minimum 2-year follow-up) with ASD who underwent long-segment fusion from T10 to sacrum with sacropelvic fixation. Patients were classified into the non-RF group and the RF group. After logistic regression analysis of the risk factors for RF, subgroup analyses were performed: pedicle subtraction osteotomy (PSO) with two-rod (P2 group) versus PSO with two-rod and AR (P4 group), and LLIF with two-rod (L2 group) versus LLIF with two-rod and AR (L4 group).

Results.
RF occurred in 50 patients (21%) at an average of 25 months. RF occurred more frequently in patients who underwent PSO than in those who underwent LLIF (P=0.002), and the use of the AR technique was significantly higher in the non-RF group (P<0.05).
Following logistic regression analysis, preoperative PI-LL mismatch, PSO, and the AR technique were associated with RF. In subgroup analyses, RF incidence was 65% (24/37 cases) of the P2 group, 8% (4/51 cases) of the P4 group, and 21% (22/105 cases) of the L2 group. In the L4 group, there was no RF.

Conclusion.
Minimally invasive multilevel LLIF with the AR technique is capable of as much LL correction as conventional PSO and appears to be an effective method for reducing RF.
Perioperative pain management for appendicectomy
Authors: Freys Jacob C. , Bigalke Stephan M. , Mertes Moritz , Lobo Dileep N. , Pogatzki-Zahn Esther M. , Freys Stephan M. ,   The PROSPECT Working Group of the European Society of Regional Anaesthesia and Pain Therapy (ESRA)‡
Published: January 2024

BACKGROUND
Despite being a commonly performed surgical procedure, pain management for appendicectomy is often neglected because of insufficient evidence on the most effective treatment options.

OBJECTIVE
To provide evidence-based recommendations by assessing the available literature for optimal pain management after appendicectomy.

DESIGN AND DATA SOURCES
This systematic review-based guideline was conducted according to the PROSPECT methodology. Relevant randomised controlled trials, systematic reviews and meta-analyses in the English language from January 1999 to October 2022 were retrieved from MEDLINE, Embase and Cochrane Databases using PRISMA search protocols.

ELIGIBILITY CRITERIA
We included studies on adults and children. If articles reported combined data from different surgeries, they had to include specific information about appendicectomies. Studies needed to measure pain intensity using a visual analogue scale (VAS) or a numerical rating scale (NRS). Studies that did not report the precise appendicectomy technique were excluded.

RESULTS
Out of 1388 studies, 94 met the inclusion criteria. Based on evidence and consensus, the PROSPECT members agreed that basic analgesics [paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs)] should be administered perioperatively for open and laparoscopic appendicectomies. A laparoscopic approach is preferred because of lower pain scores. Additional recommendations for laparoscopic appendicectomies include a three-port laparoscopic approach and the instillation of intraperitoneal local anaesthetic. For open appendicectomy, a preoperative unilateral transverse abdominis plane (TAP) block is recommended. If not possible, preincisional infiltration with local anaesthetics is an alternative. Opioids should only be used as rescue analgesia. Limited evidence exists for TAP block in laparoscopic appendicectomy, analgesic adjuvants for TAP block, continuous wound infiltration after open appendicectomy and preoperative ketamine and dexamethasone. Recommendations apply to children and adults.

CONCLUSION
This review identified an optimal analgesic regimen for open and laparoscopic appendicectomy. Further randomised controlled trials should evaluate the use of regional analgesia and wound infiltrations with adequate baseline analgesia, especially during the recommended conventional three-port approach.

REGISTRATION
The protocol for this study was registered with the PROSPERO database (Registration No. CRD42023387994).
Differential Mortality Among Heart Failure Patients Across Different COVID-19 Surges in New York City
Authors: Mathai Sheetal Vasundara , Apple Samuel J. , Xu Xiaobao , Pang Li , Flatow Elie , Friedman Ari , Rios Saul , Benites Moya Cesar Joel , Alhuarrat Majd Al Deen , Parker Matthew , Sokol Seth I. , Faillace Robert T. 
Published: January 2024

ABSTRACT
Learning from the healthcare system's response to the COVID-19 pandemic is essential to better prepare for potential future crises. We sought to assess mortality rates for patients admitted for acute decompensated heart failure (HF) and to analyze which factors demonstrated a statistically significant correlation with this primary endpoint. We performed a retrospective analysis of patients hospitalized with a primary diagnosis of acute decompensated HF within the New York City Health and Hospitals 11-hospital system across the different COVID surge periods. Mortality information was collected in 4,405 participants (mean [SD] age 70.54 [14.44] years, 1885 [42.87%] female).The highest mortality existed in the first surge (9.02%), then improved to near prepandemic levels (3.65%) in the second (3.91%) and third surges (5.94%, p < 0.0001). In-hospital mortality inversely correlated with receipt of a COVID-19 vaccination, but had no correlation with left ventricular ejection fraction or the number of vaccination doses. Mortality for acute decompensated HF patients improved after the first surge, suggesting that hospitals adequately adapted to provide quality care. As future infectious outbreaks may occur, emergency preparedness must ensure that adequate focus and resources remain for other clinical entities, such as HF, to ensure optimal care is delivered across all areas of illness.
Eliminating Hands-Off Handoffs: Improvement in Perioperative Handoff Communication With a Multidisciplinary Tool Initiative
Authors: Ebertz David P. , Steinhagen Emily , Alvarado Christine E. , Bingmer Katherine , Asher Daniel , Berardinelli Amy , Ammori John 
Published: January 2024

ABSTRACT

Introduction:
Handoffs between the operating room (OR) and post-anesthesia care unit (PACU) require a high volume and quality of information to be transferred. This study aimed to improve perioperative communication with a handoff tool.

Methods:
Perioperative staff at a quaternary care center was surveyed regarding perception of handoff quality, and OR to PACU handoffs were observed for structured criteria. A 25-item tool was implemented, and handoffs were similarly observed. Staff was then again surveyed. A multidisciplinary team led this initiative as a collaboration.

Results:
After implementation, nursing reported improved perception of time spent (2.63–3.68, p = .02) and amount of information discussed (2.85–3.73, p = .05). Anesthesia also reported improved personal communication (3.69–4.43, p = .004), effectiveness of handoffs (3.43–3.82, p = .02), and amount of information discussed (4.26–4.76, p = .05). After implementation, observed patient information discussed during handoffs increased for both surgical and anesthesia team members. The frequency of complete and near-complete handoffs increased (40%–74%, p < .001).

Conclusions:
A structured handoff tool increased the amount of essential information reported during handoffs between the OR and PACU and increased team members' perception of handoffs.
A de novo variant in ZBTB18 gene caused autosomal dominant non-syndromic intellectual disability 22 syndrome: A case report and literature review
Authors: Yang Fan , Ding Yu , Wang Yirou , Zhang Qingwen , Li Hao , Yu Tingting , Chang Guoying , Wang Xiumin 
Published: January 2024

Rationale:
Autosomal dominant non-syndromic intellectual disability 22 is a rare genetic disorder caused by the ZBTB18 gene. This disorder affects various parts of the body, leading to intellectual disability. It is noteworthy that only 31 cases of this disorder have been reported thus far. As the symptom severity may differ, doctors may face challenges in diagnosing it accurately. It is crucial to be familiar with this disorder’s symptoms to receive proper diagnosis and essential medical care.

Patient concerns:
There is a case report of a 6-year-old boy who had an unexplained thyroid abnormality, global developmental delay, and an abnormal signal of white matter in brain MRI. However, he did not have growth retardation, microcephaly, corpus callosum hypoplasia, epilepsy, or dysmorphic facial features. Clinical whole exome sequencing revealed a de novo pathogenic variant in the ZBTB18 gene (c.1207delC, p. Arg403Alafs*60), which is a previously unreported site. This variant causes the premature termination of peptide chain synthesis, leading to incomplete polypeptide chains.

Diagnoses:
Autosomal dominant non-syndromic intellectual and disability 22 syndrome and thyroid dysfunction.

Interventions:
Rehabilitation training.

Outcomes:
The individual is experiencing difficulty with their motor skills, appearing clumsier while running. He struggles with expressing themselves and forming complete sentences, relying mostly on gestures and pointing.

Lessons:
The clinical presentations of mental retardation, autosomal dominant, type 22 (MRD22) are complicated and varied. Although early diagnosis can be made according to typical clinical symptoms, whole exome sequencing is necessary for diagnosing MRD22, as our study indicates.