bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of luciferase-expressing Neospora caninum and drug screening
Authors: Wang Fei , Xue Yangfei , Pei Yanqun , Yin Meng , Sun Zhepeng , Zhou Zihui , Liu Jing , Liu Qun 
Published: March 2024

Abstract
Background
Neospora caninum is an apicomplexan parasite that is particularly responsible for abortions in cattle and neuromuscular disease in dogs. Due to the limited effectiveness of currently available drugs, there is an urgent need for new therapeutic approaches to control neosporosis. Luciferase-based assays are potentially powerful tools in the search for antiprotozoal compounds, permitting the development of faster and more automated assays. The aim of this study was to construct a luciferase-expressing N. caninum and evaluate anti-N. caninum drugs.

Methods
Luciferase-expressing N. caninum (Nc1-Luc) was constructed using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). After testing the luciferase expression and phenotype of the Nc1-Luc strains, the drug sensitivity of Nc1-Luc strains was determined by treating them with known positive or negative drugs and calculating the half-maximal inhibitory concentration (IC50). The selective pan-rapidly accelerated fibrosarcoma (pan-RAF) inhibitor TAK-632 was then evaluated for anti-N. caninum effects using Nc1-Luc by luciferase activity reduction assay and other in vitro and in vivo studies.

Results
The phenotypes and drug sensitivity of Nc1-Luc strains were consistent with those of the parental strains Nc1, and Nc1-Luc strains can be used to determine the IC50 for anti-N. caninum drugs. Using the Nc1-Luc strains, TAK-632 showed promising activity against N. caninum, with an IC50 of 0.6131 μM and a selectivity index (SI) of 62.53. In vitro studies demonstrated that TAK-632 inhibited the invasion, proliferation, and division of N. caninum tachyzoites. In vivo studies showed that TAK-632 attenuated the virulence of N. caninum in mice and significantly reduced the parasite burden in the brain.

Conclusions
In conclusion, a luciferase-expressing N. caninum strain was successfully constructed, which provides an effective tool for drug screening and related research on N. caninum. In addition, TAK-632 was found to inhibit the growth of N. caninum, which could be considered as a candidate lead compound for new therapeutics for neosporosis.

Graphical Abstract
Late cardiotoxicity related to HER2-targeted cancer therapy
Authors: Senechal Isabelle , Andres Maria Sol , Tong Jieli , Perone Ylenia , Ramalingam Sivatharshini , Nazir Muhummad Sohaib , Rosen Stuart D , Turner Nicholas , Ring Alistair , Lyon Alexander R 
Published: March 2024

AbstractLong-term anti-HER2 therapy in metastatic HER2 + cancers is increasing, but data about the incidence and risk factors for developing late Cancer therapy-related cardiac dysfunction (CTRCD) are missing. We conducted a single-centre, retrospective analysis of a cohort of late anti-HER2 related cardiac dysfunction referred to our Cardio-Oncology service. We include seventeen patients with metastatic disease who developed CTRCD after at least five years of continuous anti-HER2 therapy. Events occurred after a median time of 6.5 years (IQR 5.3-9.0) on anti-HER2 therapy. The lowest (median) LVEF and GLS were 49% (IQR 45–55) and − 15.4% (IQR − 14.9 - -16.3) respectively. All our patients continued or restarted, after a brief interruption, their anti-HER2 therapy. Most (16/17) were started on heart failure medical therapy and normalized their left ventricular ejection fraction at a follow-up. Our study has demonstrated that CTRCD can occur after many years of stability on anti-HER2 therapy and reinforces the importance of continuing cardiovascular surveillance in this population.
The spectrum of TP53 mutations in Rwandan patients with gastric cancer
Authors: Nzitakera Augustin , Surwumwe Jean Bosco , Ndoricyimpaye Ella Larissa , Uwamungu Schifra , Uwamariya Delphine , Manirakiza Felix , Ndayisaba Marie Claire , Ntakirutimana Gervais , Seminega Benoit , Dusabejambo Vincent , Rutaganda Eric , Kamali Placide , Ngabonziza François , Ishikawa Rei , Rugwizangoga Belson , Iwashita Yuji , Yamada Hidetaka , Yoshimura Kimio , Sugimura Haruhiko , Shinmura Kazuya 
Published: March 2024

Abstract
Background
Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer.

Results
Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon–intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed.

Conclusions
Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.
A structured, journal-led peer-review mentoring program enhances peer review training
Authors: Lyons-Warren Ariel Maia , Aamodt Whitley W. , Pieper Kathleen M. , Strowd Roy E. 
Published: March 2024

Abstract
Background
Peer review is essential to the advancement of knowledge. However, training on how to conduct peer review is limited, unorganized, and not well studied. Thus, we sought to determine if a structured mentored peer-review program improved peer review training as measured by multiple quantitative and qualitative assessments.

Methods
This pre-post intervention study enrolled 55 mentees across 5 cohorts from 2020 to 2023. Each cohort completed pre-program evaluations, participated in 2 mentored reviews, and completed post-program evaluations over 6 months. Mentors and mentees completed pre-program demographic and review experience questionnaires. Outcome measures included (1) total and sub-scores on the modified Review Quality Index (mRQI) applied to the same pre-selected research manuscript reviewed by mentees both pre and post intervention, (2) mentee self-perceived comfort with and understanding of the review process using a custom questionnaire, and (3) mentor satisfaction surveys. Pre- and post-program measures were compared using the Wilcoxon signed-rank test.

Results
Post-program total modified RQI score (median (IQR) = 31 (26.3–35.8)) was higher than pre-program total score (26.6 (19.7–29.7)) for the 42 mentees who completed both pre- and post-program reviews. Mentees reported improved perception of review (median (IQR) pre = 4 (3–4), post = 5 (4–5)) and editorial processes (pre = 3 (2–4), post = 4 (4–5)) as well as self-perceived confidence in completing an independent review of both scientific (median (IQR) pre = 2 (2–3), post = 4 (4–4)) and non-scientific (pre = 3 (2–4), post = 4 (4–5)) manuscripts following program participation. p < 0.0001 for all scores noted. Mentors reported high scores for enjoyment (median (range) 5/5 (3–5)) and interest in repeat participation (5/5 (2–5)).

Conclusions
A 6-month structured mentored-review program including 2 mentored reviews improves peer review training as measured by the modified RQI as well as participant self-perceived understanding of publication science with high mentor satisfaction.
Safe system for sustainable development
Authors: Lah Oliver 
Published: March 2024

AbstractThis paper presents a novel governance concept for sustainable development, introducing the 'Safe System Approach' as a transformative model that shifts focus from individual behavioural change to systemic transformation. This approach challenges traditional governance models that emphasize individual responsibility in achieving sustainable development and decarbonization. Instead, it advocates for creating an enabling environment that inherently guides individuals and communities towards sustainable actions. The Safe System Approach is centred on delivering low-carbon services across essential sectors, including electricity, mobility, industry, buildings, human settlements, and agriculture, thereby embedding sustainability as a default choice in societal systems. Drawing parallels with successful models in road safety, the paper explores the potential of this approach in urban development and climate action. It emphasizes the need for a broad coalition and integrated approaches in managing shared resources, highlighting the significance of systemic adjustments over individual behavioral change. By proposing a structure where sustainability is facilitated by the system's design, the paper builds on key concepts from seminal works by scholars like Garrett Hardin, Mancur Olson, Elinor Ostrom, and Ahrend Lijphart. It discusses the challenges and opportunities in creating safe operating spaces for sustainable development, emphasizing the need for multi-actor, multilevel governance systems that can manage shared resources sustainably and are resilient to political volatility. The paper aims to offer a robust, efficient, and inclusive pathway to sustainable development, contributing to the global discourse on environmental and social resilience.
Assessment of brain-derived neurotrophic factor levels in serum of children with autism spectrum disorders
Authors: Elhamid Salwa Amin Abd , Alkherkhisy Mohammad Mostafa , Kasem Rania Elsayed 
Published: March 2024

Abstract
Background
The autism spectrum disorder (ASD) has no identified biomarker for early detection or for its severity. As for the brain-derived neurotrophic factor (BDNF), it is a crucial neurotropic factor that regulates the plasticity and maturing of neuronal synapses. Accordingly, it might influence how children with autism develop.

Method
To evaluate the BDNF serum levels in autistic children and their relationship with the illness severity as well as with the common drugs received by autistic patients, 60 patients with autism along with another 60 normally developing children were involved in the study. Using the Childhood Autism Rating Scale (CARS), the severity of autism was then evaluated. The ELISA method was used to measure the BDNF level.

Results
It was seen that the BDNF concentrations were higher in autism patients (P < 0.001). There was also a highly strong positive association between the CARS score and the BDNF (P < 0.001). Using the cut-off value of > 2.8 of BDNF helped to distinguish between well-developing and autistic children, with the aspects of “sensitivity” and “specificity” being 88.3% and 80%, respectively. Moreover, children with autism who received omega-3 had statistically lower levels of BDNF than those who did not take any (P = 0.040).

Conclusion
The serum BDNF concentration is higher in autism; this proposes that the BDNF may contribute to the onset or progress of autism. Therefore, it may be used as a noninvasive biomarker for the illness severity because of its greater occurrence in autistic children who have severe social impairment.
PET-CT-based resection guide for treatment of auricular squamous cell carcinoma: an innovative clinical management of soft tissue tumors: a case report
Authors: Mekky Mohamed , Nawwar Muhammad A. , Nabawi Ayman Sameh , Aziz Mahmoud Yehya Abdul , Galal Ahmed , Sleem Heba 
Published: March 2024

Abstract
Purpose
To describe the successful use of a PET-CT-based resection guide for the treatment of auricular squamous cell carcinoma.

Case presentation
A 69-year-old male presented with a painless growing mass in his left ear helix that had been unsuccessfully treated conservatively by another surgeon. An incisional biopsy revealed moderately differentiated squamous cell carcinoma, and the patient was referred to the department for further management. A PET/CT was performed, which showed uptake of FDG in the ear with a SUV max value and T3N0M0 status. The treatment plan was based on a multidisciplinary team discussion and a thorough evaluation of the PET/CT imaging findings. A decision was made to proceed with excision of the mass with a wide safety margin, using a PET/CT-based resection guide for ear resection. Additionally, partial temporal bone resection, selective neck dissection, and superficial parotidectomy were planned. The patient opted for reconstruction with a scalp rotational flap. The patient’s treatment plan was successful, and at follow-up visits, he remained disease-free. This case report highlights the importance of using a PET-CT-based resection guide for the treatment of soft tissue tumors, specifically auricular squamous cell carcinoma. It also demonstrates the importance of a multidisciplinary team approach and thorough evaluation of imaging findings in determining an effective treatment plan for patients.

Conclusions
The use of PET-CT-based resection guide can be an effective tool in the treatment of auricular squamous cell carcinoma. It can provide more precise and accurate information about the extent of the tumor, leading to a more effective treatment plan. Multidisciplinary team approach and thorough evaluation of imaging findings are crucial in determining the best course of treatment for patients.
Shell game with a quantum pea
Authors: Yi Juyeon 
Published: March 2024

Abstract
We examine the role of quantum measurement and coherence, considering the shell game with a quantum particle. The game consists of three sites arranged to form a ring geometry and a particle visiting the sites through a unitary evolution. A player selects one of the sites as a target site and wins if the target site contains the particle at a preassigned time. The player has two options for determining win or loss: local and global measurements, which perform projective measurements on the occupancy of the target site and the particle's position, respectively. The game can be played over multiple rounds, and each round begins with the state reached at the end of the previous round. We calculate the probability of winning at each round and the probability of consecutive losses and find that those probabilities have characteristic asymptotes. We obtain the analytic expressions of the asymptote and scrutinize their essential dependence on the measurement options and coherence in the initial ensemble.
One-for-all: Support-free optimized Fourier random phase for real-time multiple kinoforms generation
Authors: Zhang Cheng , Zhou Hao , Wu Feng , Han Peng , Shi Jisen , Yang Hairong , Hong Cheng , Shen Chuan , Wei Sui 
Published: March 2024

Abstract
Existing optimized random phase (ORAP) approach mainly faces the limitations of fixed supports. Different ORAPs need to be generated for different target images with different support sizes, thus lacking flexibility and severely limiting applicability. This paper proposes a support-free optimized Fourier random phase (SF-OFRAP) approach for non-iterative kinoform generation, which greatly improves the speed and flexibility of generating kinoforms, and can achieve comparable performance to the ORAP approach. The proposed SF-OFRAP approach not only breaks the fixed support constraint of a target image, but can generate kinoforms of target images with different shapes, different positions, etc. with arbitrary supports. Our proposed SF-OFRAP approach can achieve real-time generation of kinoforms for multi-view holographic display using only a single generated SF-OFRAP without the need for additional phase compensation. The SF-OFRAP approach is suitable for real-time holographic display. Experiments verified the superiority of the produced SF-OFRAP over the ORAP method in terms of flexibility and adaptability to multiple different objects in different positions and different shapes using only one kind of these. The experimental results verify the effectiveness and excellent flexibility of SF-OFRAP for video holographic display and multi-view holographic display.
The Search for the Causes of Common Hyperandrogenism, 1965 to Circa 2015
Authors: Rosenfield Robert L 
Published: March 2024

Abstract
From 1965 to 2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and the elevation of an index of the plasma free testosterone concentration in most hirsute women. The molecular genetic basis, though not the developmental biologic basis, for adrenarche is now known and 11-oxytestosterones shown to be major bioactive adrenal androgens. The evolution of the lines of research into the pathogenesis of PCOS is historically traced: research milestones are cited in the areas of neuroendocrinology, insulin resistance, hyperinsulinism, type 2 diabetes mellitus, folliculogenesis, androgen secretion, obesity, phenotyping, prenatal androgenization, epigenetics, and complex genetics. Large-scale genome-wide association studies led to the 2014 discovery of an unsuspected steroidogenic regulator DENND1A (differentially expressed in normal and neoplastic development). The splice variant DENND1A.V2 is constitutively overexpressed in PCOS theca cells in long-term culture and accounts for their PCOS-like phenotype. The genetics are complex, however: DENND1A intronic variant copy number is related to phenotype severity, and recent data indicate that rare variants in a DENND1A regulatory network and other genes are related to PCOS. Obesity exacerbates PCOS manifestations via insulin resistance and proinflammatory cytokine excess; excess adipose tissue also forms testosterone. Polycystic ovaries in 40 percent of apparently normal women lie on the PCOS functional spectrum. Much remains to be learned.
Cadherin-dependent adhesion is required for muscle stem cell niche anchorage and maintenance
Authors: Hung Margaret , Lo Hsiao-Fan , Beckmann Aviva G. , Demircioglu Deniz , Damle Gargi , Hasson Dan , Radice Glenn L. , Krauss Robert S. 
Published: March 2024

ABSTRACT
Adhesion between stem cells and their niche provides stable anchorage and signaling cues to sustain properties such as quiescence. Skeletal muscle stem cells (MuSCs) adhere to an adjacent myofiber via cadherin-catenin complexes. Previous studies on N- and M-cadherin in MuSCs revealed that although N-cadherin is required for quiescence, they are collectively dispensable for MuSC niche localization and regenerative activity. Although additional cadherins are expressed at low levels, these findings raise the possibility that cadherins are unnecessary for MuSC anchorage to the niche. To address this question, we conditionally removed from MuSCs β- and γ-catenin, and, separately, αE- and αT-catenin, factors that are essential for cadherin-dependent adhesion. Catenin-deficient MuSCs break quiescence similarly to N-/M-cadherin-deficient MuSCs, but exit the niche and are depleted. Combined in vivo, ex vivo and single cell RNA-sequencing approaches reveal that MuSC attrition occurs via precocious differentiation, re-entry to the niche and fusion to myofibers. These findings indicate that cadherin-catenin-dependent adhesion is required for anchorage of MuSCs to their niche and for preservation of the stem cell compartment. Furthermore, separable cadherin-regulated functions govern niche localization, quiescence and MuSC maintenance.
Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial
Authors: Goetze Thorsten O. , Reichart Alexander , Bankstahl Ulli S. , Pauligk Claudia , Loose Maria , Kraus Thomas W. , Elshafei Moustafa , Bechstein Wolf O. , Trojan Jörg , Behrend Matthias , Homann Nils , Venerito Marino , Bohle Wolfram , Varvenne Michael , Bolling Claus , Behringer Dirk M. , Kratz-Albers Karsten , Siegler Gabriele M. , Hozaeel Wael , Al-Batran Salah-Eddin 
Published: March 2024

Abstract
Background
Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer.

Patients and Methods
This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS).

Results
Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms.

Conclusions
Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.