bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of patients receiving vertebral body tethering for adolescent idiopathic scoliosis in the public and private hospital setting
Authors: Ng Samuel , Changmeng Zhang , Cheung Jason , Shea Graham Ka Hon 
Published: November 2024

Abstract
Purpose
Vertebral body tethering (VBT) is a new growth-modulating surgery for adolescent idiopathic scoliosis (AIS) requiring a distinct skillset and intraoperative setup. We compared perioperative details and outcomes of VBTs performed in a public pediatric orthopedic hospital and a general private hospital setting.

Methods
We identified all patients receiving VBT for AIS from 1/2020 to 12/2023 with ≥ 6 months post-operative follow-up, with surgeries performed by the same senior surgeons. Clinical, radiological, and surgical details were retrieved.

Results
24 VBTs were performed in the private setting and 16 in the public setting. Average age at operation was 11.9 ± 1.1 at a Sanders staging of 3.8 ± 1.2 when the major curve Cobb angle was 50.5 ± 8.0°. Tethered curves were most often thoracic in location (23/40) followed by thoracolumbar/lumbar curves (10/40) and double curve tethers (7/40). Overall correction ratio of 68.0 ± 19.0% was achieved. Time from booking to operation (82.2 ± 39.2 vs 63.1 ± 34.4 days, p = 0.112) and operation time (310 ± 86.4 min vs. 289 ± 87.4 min, p = 0.054) were longer in the public and private setting respectively but failed to reach statistical significance. Time to chest drain removal (1.5 ± 0.8 vs. 3.5 ± 1.7 days, p < 0.001) and length of stay (4.3 ± 0.9 vs. 6.6 ± 1.8 days, p < 0.001) were significantly shorter in the private setting, whilst complication rates remained similar (7/24 vs. 3/16, p = 0.456).

Conclusion
Expertise, resource availability, and costs differ in the public and private healthcare setting. With regards to VBT, the conditions for referral and surgical outcomes remained similar. Earlier drain removal and discharge for patients managed in the private setting was not associated with an increase in complication rate.
Pedunculoside alleviates cognitive deficits and neuronal cell apoptosis by activating the AMPK signaling cascade
Authors: Li Liwei , Sun Jinfeng , Chen Fan , Xiong Li , She Lingyu , Hao Tang , Zeng Yuqing , Li Luyao , Wang Wei , Zhao Xia , Liang Guang 
Published: November 2024

Abstract
Background
Mitochondrial dysfunction emerges as an early pathological hallmark of Alzheimer's disease (AD). The reduction in mitochondrial membrane potential and the elevation of reactive oxygen species (ROS) production are pivotal in the initiation of neuronal cell apoptosis. Pedunculoside(Ped), a novel triterpene saponin derived from the dried barks of Ilex rotunda Thunb, exhibits a potent anti-inflammatory effect. In the course of drug screening, we discovered that Ped offers significant protection against apoptosis induced by Aβ1-42. Nevertheless, the role and mechanism of Ped in AD are yet to be elucidated.

Methods
Oxidative stress was evaluated by measuring mitochondrial membrane potential and intracellular ROS production. The expression of proteins associated with apoptosis was determined using western blot analysis and flow cytometry. In vivo, the pathological characteristics of AD were investigated through Western blot and tissue immunofluorescence techniques. Cognitive function was assessed using the Morris Water Maze and Novel Object Recognition tests.

Results
We demonstrated that Ped decreased apoptosis in PC12 cells, reduced the generation of intracellular ROS, and restored mitochondrial membrane potential. Mechanistically, we found that the protective effect of Ped against Aβ-induced neurotoxicity was associated with activation of the AMPK/GSK-3β/Nrf2 signaling pathway. In vivo, Ped alleviated memory deficits and inhibited neuronal apoptosis, inflammation, and oxidative stress in the hippocampus of 3 × Tg AD mice, along with the activation of the AMPK signaling pathway.

Conclusion
The findings indicate that Ped exerts its neuroprotective effects against oxidative stress and apoptosis through the AMPK signaling cascade. The results demonstrate that Ped is a potential candidate for the treatment of AD.

Graphical Abstract
Engineering Saccharomyces cerevisiae for the production of natural osmolyte glucosyl glycerol from sucrose and glycerol through Ccw12-based surface display of sucrose phosphorylase
Authors: Martinić Cezar Tea , Marđetko Nenad , Trontel Antonija , Paić Antonia , Slavica Anita , Teparić Renata , Žunar Bojan 
Published: November 2024

Abstract
Background
Yeast Saccharomyces cerevisiae is widely recognised as a versatile chassis for constructing microbial cell factories. However, producing chemicals from toxic, highly concentrated, or cell-impermeable substrates, or chemicals dependent on enzymatic reactions incompatible with the yeast’s intracellular environment, remains challenging. One such chemical is 2-O-(α-D-glucopyranosyl)-sn-glycerol (glucosyl glycerol, αGG), a natural osmolyte used in the cosmetics and healthcare industries. This compound can be synthesised in a one-enzyme reaction from sucrose and glycerol by Leuconostoc mesenteroides sucrose phosphorylase (SucP), an enzyme which, in a low-water, glycerol-rich, phosphate-free environment, transfers the glucosyl moiety from sucrose to glycerol.

Results
In this study, we engineered a yeast microbial cell factory for αGG production. For this purpose, we first focused on the abundant yeast GPI-anchored cell wall protein Ccw12 and used our insights to develop a miniature Ccw12-tag, which adds only 1.1 kDa to the enzyme of interest while enabling its covalent attachment to the cell wall. Next, we Ccw12-tagged SucP and expressed it in an invertase-negative strain of yeast S. cerevisiae from the PHO5 promoter, i.e., promoter strongly induced under phosphate-free conditions. Such SucP isoform, covalently C-terminally anchored to the outer cell surface, produced extracellularly 37.3 g l− 1 (146 mM) of αGG in five days, while the underlying chassis metabolised reaction by-products, thereby simplifying downstream processing.

Conclusions
The here-described S. cerevisiae strain, displaying C-terminally anchored sucrose phosphorylase on its cell surface, is the first eukaryotic microbial cell factory capable of a one-step αGG production from the readily available substrates sucrose and glycerol.
Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities
Authors: Takemon Yuka , Pleasance Erin D. , Gagliardi Alessia , Hughes Christopher S. , Csizmok Veronika , Wee Kathleen , Trinh Diane L. , Huff Ryan D. , Mungall Andrew J. , Moore Richard A. , Chuah Eric , Mungall Karen L. , Lewis Eleanor , Nelson Jessica , Lim Howard J. , Renouf Daniel J. , Jones Steven JM. , Laskin Janessa , Marra Marco A. 
Published: November 2024

Abstract
Background
Loss-of-function (LOF) alterations in tumour suppressor genes cannot be directly targeted. Approaches characterising gene function and vulnerabilities conferred by such mutations are required.

Methods
Here, we computationally map genetic networks of KMT2D, a tumour suppressor gene frequently mutated in several cancer types. Using KMT2D loss-of-function (KMT2DLOF) mutations as a model, we illustrate the utility of in silico genetic networks in uncovering novel functional associations and vulnerabilities in cancer cells with LOF alterations affecting tumour suppressor genes.

Results
We revealed genetic interactors with functions in histone modification, metabolism, and immune response and synthetic lethal (SL) candidates, including some encoding existing therapeutic targets. Notably, we predicted WRN as a novel SL interactor and, using recently available WRN inhibitor (HRO761 and VVD-133214) treatment response data, we observed that KMT2D mutational status significantly distinguishes treatment-sensitive MSI cell lines from treatment-insensitive MSI cell lines.

Conclusions
Our study thus illustrates how tumour suppressor gene LOF alterations can be exploited to reveal potentially targetable cancer cell vulnerabilities.
Food, nutrition and sustainability education in Australian primary schools: a cross-sectional analysis of teacher perspectives and practices
Authors: Kempler Jessica V , Margerison Claire , Nanayakkara Janandani , Booth Alison 
Published: November 2024

Abstract
Background
Healthy eating patterns from sustainable food systems are crucial for population and planetary health. Primary schools are opportune settings for teaching children about food, nutrition and sustainability (FNS) though little is known about the delivery of FNS education in this sector. This study aimed to analyse current approaches to FNS education in Australian primary schools.

Methods
A cross-sectional online survey with closed- and open-ended questions collected data about (i) teacher perceptions and attributes regarding FNS education; (ii) FNS teaching practices; and (iii) factors influencing FNS education. Statistical analyses were conducted using STATA including descriptive statistics and chi-square analyses to test for associations between categorical variables. Qualitative content and thematic analyses of open-ended questions were conducted using NVivo 14.

Results
Participants were 413 Australian primary school teachers. Teachers considered FNS education as equally important to most curriculum subjects, though frequency of FNS education was low. Less than a third of teachers were trained in FNS education, had access to funding for FNS-related activities or were from schools with policies about including FNS education in the curriculum. There was a significant association between frequency of FNS education and teacher training, access to funding and presence of FNS curriculum policies (all p < 0.001). Teachers who were trained to teach nutrition, food skills or food sustainability (all p < 0.05) were more likely to teach this as both stand-alone and cross-curricular subjects. Teachers described personal factors (workload, stress, scope of practice) that influenced their FNS teaching practices, as well as factors related to students’ families (family responsibility for FNS education, family food practices, family engagement in FNS activities), the curriculum (overcrowding, prioritisation, access to resources) and the broader school environment (time, facilities, funding, training).

Conclusions
Strengthening the position of FNS education in the primary school sector is an important next step for public health research, policy and practice. Researchers and policy makers should explore future opportunities for training, funding and policy approaches that prioritise FNS within the primary school curriculum and in everyday teaching practice.
Dietary inclusion of fibrous corn silages reduces gastric mucosa damage in fattening heavy pigs
Authors: Spanghero M. , Braidot M. , Orioles M. , Sarnataro C. , Pividori I. , Romanzin A. 
Published: November 2024

Abstract
Background
Several surveys conducted at slaughter sites have highlighted that gastric lesions are a widespread issue in fattening pigs, mainly due to feeding regimes. Diets with small particle sizes and low fibre contents guarantee high digestibility and performance but generate more rapid stomach emptying with a negative effect on gastric mucosa integrity. Providing fattening pigs with fibrous materials (e.g., straw provided in racks) or coarse fibrous ingredients (e.g., coarse silages) reduced the presence of gastric ulcers. The present research compares a traditional corn-soy-based diet with an experimental diet where bran and a portion of corn meal was substituted with whole ear and whole plant corn silages at the maximum dosages permitted by new Protected Designation of Origin for Italian dry-cured ham (20 and 10% of DM, respectively). This study aimed to examine the impact of the inclusion of corn silages in the diet on the productive performance of heavy Italian pigs and their ability to mitigate gastric mucosa damage.

Results
The growth performances were satisfactory (750–800 g/d) given the advanced interval of growth of animals (from 120 to 180 kg). However, the inclusion of corn silages tended to reduce the growth rate by 5–6% due to the reduction of organic matter digestibility, without compromising the slaughter traits or the back-fat fatty acid profile. The experimental diet substantially affected both stomach development and mucosal integrity. The first consequence was an increase in stomach weight of approximately 6% (P < 0.01) but the most notable advantage of coarse feeding was a reduction in stomach damage severity, with a low number of cases with higher scores in animals fed coarse materials (P < 0.01).

Conclusions
The dietary inclusion of corn silages (30% of diet DM) decrease effectivelly the severity of stomach damage in finishing heavy pigs. Based on the feeding trial performances, the perspective of feeding heavy pigs corn silage should consider specific agronomic and harvesting techniques to improve digestibility and not reduce the growth rate.
Clinical and pathological characteristics in 214 Danish weaners euthanized because of umbilical outpouchings
Authors: Hansen Marie-Louise , Larsen Inge , Jensen Tina Birk , Kristensen Charlotte Sonne , Pedersen Ken Steen 
Published: November 2024

Abstract
Background
Umbilical outpouchings (UO) are common in Danish weaners. In slaughter pigs UOs consist of various pathological diagnoses; however, no studies have assessed the pathology in weaners from randomly selected herds, nor the agreement between clinical examination findings and post-mortem results. The primary objective was to estimate the prevalence of UO-related clinical findings in weaners before euthanasia and the pathologic macroscopic findings after euthanasia. A secondary objective was to assess the agreement between the size of the UO, the presence of ulcers, and the diagnosis before and after euthanasia. Pigs were selected for euthanasia and included in the study because the individual farmer believed the pigs were already unfit for transport, would not make it to slaughter, or would become unsellable.

Results
In total 214 weaners euthanized due to UOs were examined both clinically and post-mortem. Clinically 65.4% of the UOs were large (≥ 11 cm) and 52.3% were unreducible. In the autopsy 78.5% of the UOs were large, and 54.2% had ulcers on their UO. The most prevalent pathological diagnoses were hernia (36.4%), hernia combined with cysts/abscesses (30.8%), cysts (11.7%), and abscesses (11.2%). Adhesions were found in 32.7%, haemorrhage in 22.7%, incarcerated intestines in 8.9%, and connective tissue related to the UO in 51.9% of the pigs post-mortem. The agreement between the size of the UO in the clinical examination and post-mortem was good, as was the sensitivity and specificity for detecting ulcers in the clinical examination compared to post-mortem.

Conclusion
Hernias were the most common pathological diagnosis in weaners euthanized due to UOs, and many pigs had complications related to their UO such as ulcers, adhesions, haemorrhage, or incarcerated intestines—all conditions that could impact the pig’s welfare. The presence of connective tissue in the UO in more than half of the pigs indicated that many of the UOs had been present for an extended period. Clinical identification of the umbilical ring is difficult, but the clinical examination is useful for determining the size of the UO and the presence or absence of an ulcer, both critical factors when assessing a pig’s welfare and fitness for transport. Clinical examination, however, has limited value in determining the aetiology of UOs.
Contemporary diagnosis and treatment of valvular heart disease in Korea: a nationwide hospital-based registry study
Authors: Kim Hyung Yoon , Lee Hee Jeong , Kim In-Cheol , Son Jung-Woo , Park Jun-Bean , Lee Sahmin , Kim Eun Kyoung , Park Seong-Mi , Chung Woo-Baek , Cho Jung Sun , Park Jin-Sun , Seo Jeong-Sook , Lee Sun Hwa , Sun Byung Joo , Shim Chi Young , Kim Hyungseop , Kim Kye Hun , Kang Duk-Hyun , Ha Jong-Won ,   on behalf of the Korean Valve Survey Registry Investigators, Chung Wook-Jin , Park Chan Seok , Ahn Hyo-Suk , Cho Eun Joo , Ryu Dong Ryeol , Yang Dong Heon , Park Jeong Rang , Kim Woo-Shik , Sohn Il Suk , Na Jin Oh , Ho Hwang Sun , Ji-Yong Choi , Park Tae-Ho , Park Yong Hyun , Choi Jung Hyun , Kim Hack-Lyoung , Seo Hye Sun , Choi Eui-Young , Son Jang-Won , Kim Shin-Jae , Rhee Sang Jae , Cho In-Jeong , Byun Young Sup , Shin Sung-Hee , Yoon Se-Jung , Beom Jong Wook , Lee Ju-Hee , Bae Dae-Hwan , Kim Sung-Ai , Park Dae Gyun , Kang Min-Kyung , Hong Kyung-Soon , Heo Ran 
Published: November 2024

Abstract
Background
This study was designed to determine the current status of diagnosis and treatment of valvular heart disease (VHD) in Korea.

Methods
A nationwide registry study was conducted in 45 hospitals in Korea involving adult patients with at least moderate VHD as determined by echocardiography carried out between September and October of 2019. Of a total of 4,094 patients with at least moderate VHD, 1,482 had severe VHD (age, 71.3 ± 13.5 years; 49.1% male). Echocardiographic data used for the diagnosis of each case of VHD were analyzed. Experts from each center determined the diagnosis and treatment strategy for VHD based on current guidelines and institutional policy. The clinical outcome was in-hospital mortality.

Results
Each valve underwent surgical or transcatheter intervention in 19.3% cases of severe mitral stenosis, 31.4% cases of severe primary mitral regurgitation (MR), 7.5% cases of severe secondary MR, 43.7% cases of severe aortic stenosis, 27.5% cases of severe aortic regurgitation, and 7.2% cases of severe tricuspid regurgitation. The overall in-hospital mortality rate for patients with severe VHD was 5.4%, and for secondary severe MR and severe tricuspid regurgitation, the rates were 9.0% and 7.5%, respectively, indicating a poor prognosis. In-hospital mortality occurred in 73 of the 1,244 patients (5.9%) who received conservative treatment and in 18 of the 455 patients (4.0%) who received a surgical or transcatheter intervention, which was significantly lower in the intervention group (P = 0.037).

Conclusions
This study provides important information about the current status of VHD diagnosis and treatment through a nationwide registry in Korea and helps to define future changes.
Genomic Alterations in DNA Mismatch Repair Genes Across Different Cancer Types
Authors: Holla Vijaykumar R. , Kahle Michael P. , Kim Sun-Hee , Ronaghy Arash , Yang Richard K. , Patel Keyur P. , Routbort Mark J. , Overman Michael J. , Dumbrava Ecaterina E. , Mills Shaw Kenna R. , Karp Daniel D. , Meric-Bernstam Funda 
Published: November 2024

PURPOSE
PD-1 inhibition is effective in patients with mismatch repair deficient (dMMR) solid tumors in a tumor-agnostic fashion. However, dMMR testing by immunohistochemistry (IHC) is not routinely performed across tumor types. By contrast, next-generation sequencing (NGS) for somatic genomic alterations is frequently performed across tumor types. We hypothesized that NGS would identify patients with alterations in mismatch repair (MMR) genes and that these patients would have higher rates of MMR protein loss by IHC. This would support the utility of IHC reflex testing after NGS and potential matching to approved therapeutic options.

METHODS
From January 2016 to December 2021, 15,701 patients with solid tumors received NGS covering the MMR genes, and 4,994 patients had both IHC and NGS. Sequencing results were analyzed for mutations in MMR genes, tumor type distribution, and concordance with IHC results when available.

RESULTS

Six hundred and ninety-eight (4.4%) of 15,701 patients had mutations in one of the MMR genes. Mutations were found across tumor types. Three hundred and seventeen (6.3%) of 4,994 patients displayed IHC loss for at least one MMR protein. 33.8% patients (110/325) patients with MMR mutations had dMMR, compared with just 4.4% (207/4,669) patients without mutations (
P
< .001); dMMR rate varied by mutation type.

CONCLUSION
Mutations in MMR genes are found in multiple tumor types where IHC testing is not routine. Reflex IHC testing of patients carrying MMR gene mutations, especially those known or inferred to be inactivating, may identify more patients with dMMR and matched treatment options. However, dedicated IHC screening is needed to capture majority of the patients.
Safety and Efficacy of Osimertinib in Patients With Non–Small-Cell Lung Cancer and Uncommon Tumoral Epidermal Growth Factor Receptor Mutations: A Systematic Review and Single-Arm Meta-Analysis
Authors: Priantti Jonathan N. , Fujiwara Yu , Aquino de Moraes Francisco Cezar , Michelon Isabella , Castro Caio , Leighl Natasha B. , Cavalcante Ludimila , Addeo Alfredo , Bar Jair , Horita Nobuyuki , Cortellini Alessio , Nassar Amin H. , Vilbert Maysa , Naqash Abdul Rafeh 
Published: November 2024

PURPOSE

The activity of osimertinib is not fully characterized in non–small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (
EGFR
) mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic
EGFR
mutations.

METHODS

PubMed, Embase, and the Cochrane Library were searched for eligible studies reporting the efficacy and safety of osimertinib in NSCLC with uncommon
EGFR
mutations defined as any mutations other than exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Then, we performed a meta-analysis to pool survival outcomes and antitumoral activity, including intracranial (ic) response and adverse events.

RESULTS
Fifteen studies comprising 594 patients were included. The most frequently observed uncommon solitary mutations were G719X in 25% (81/327) of patients and L861Q in 21% (69/327). The most common compound mutations were G719X with T790M in 12% (23/192) of patients and G719X with S768I in 11% (22/192). Pooled analysis showed an objective response rate (ORR) of 51.30% (95% CI, 45.80 to 56.81), a disease control rate (DCR) of 90.11% (95% CI, 86.27 to 92.96), a median progression-free survival of 9.71 months (95% CI, 7.96 to 11.86), and a median overall survival of 16.79 months (95% CI, 9.93 to 28.39). icORR was 45.96% (95% CI, 30.18 to 62.17), and icDCR was 95.76% (95% CI, 69.84 to 100). Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33).

CONCLUSION

Osimertinib demonstrated robust response in NSCLC harboring uncommon
EGFR
mutations, without unanticipated safety concerns.