bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma
Authors: Zhang Nan , Yang Xu , Piao Mingjian , Xun Ziyu , Wang Yunchao , Ning Cong , Zhang Xinmu , Zhang Longhao , Wang Yanyu , Wang Shanshan , Chao Jiashuo , Lu Zhenhui , Yang Xiaobo , Wang Hanping , Zhao Haitao
Published: February 2024

Systemic therapies using programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, the prognostic factors, and their underlying mechanisms is crucial. In this review, we summarized the latest advancements in this field. Within the tumor microenvironment, PD-L1 expression is commonly utilized to predict response. Moreover, the characteristics of tumor-infiltrating lymphocytes are associated with the effectiveness of immunotherapy. Preclinical studies have identified stimulatory dendritic cells, conventional dendritic cells, and macrophages as potential biomarkers. The emergence of single-cell sequencing and spatial transcriptomics has provided invaluable insights into tumor heterogeneity through the lens of single-cell profiling and spatial distribution. With the widespread adoption of next-generation sequencing, certain genomic characteristics, including tumor mutational burden, copy number alterations, specific genes (TP53, CTNNB1, and GZMB), and signaling pathways (WNT/β-catenin) have been found to correlate with prognosis. Furthermore, clinical features such as tumor size, number, and metastasis status have demonstrated prognostic value. Notably, common indicators such as the Child-Pugh score and Eastern Cooperative Oncology Group score, which are used in patients with liver diseases, have shown potential. Similarly, commonly employed laboratory parameters such as baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes in alpha-fetoprotein (AFP) and abnormal prothrombin, CRAFITY score (composed of C-reactive protein and AFP), and immune adverse events have been identified as predictive biomarkers. Novel imaging techniques such as EOB-MRI and PET/CT employing innovative tracers also have potential. Moreover, liquid biopsy has gained widespread use in biomarker studies owing to its non-invasive, convenient, and highly reproducible nature, as well as its dynamic monitoring capabilities. Research on the gut microbiome, including its composition, dynamic changes, and metabolomic analysis, has gained considerable attention. Efficient biomarker discovery relies on continuous updating of treatment strategies. Next, we summarized recent advancements in clinical research on HCC immunotherapy and provided an overview of ongoing clinical trials for contributing to the understanding and improvement of HCC immunotherapy.
The role of thyroid function in borderline personality disorder and schizophrenia: a Mendelian Randomisation study
Authors: Babajide Oladapo , Kjaergaard Alisa D. , Deng Weichen , Kuś Aleksander , Sterenborg Rosalie B. T. M. , Åsvold Bjørn Olav , Burgess Stephen , Teumer Alexander , Medici Marco ,   German Borderline Genomics Consortium, Ellervik Christina , Nick Bass , Deloukas Panos , Marouli Eirini
Published: February 2024

Background

Genome-wide association studies have reported a genetic overlap between borderline personality disorder (BPD) and schizophrenia (SCZ). Epidemiologically, the direction and causality of the association between thyroid function and risk of BPD and SCZ are unclear. We aim to test whether genetically predicted variations in TSH and FT4 levels or hypothyroidism are associated with the risk of BPD and SCZ.

Methods

We employed Mendelian Randomisation (MR) analyses using genetic instruments associated with TSH and FT4 levels as well as hypothyroidism to examine the effects of genetically predicted thyroid function on BPD and SCZ risk. Bidirectional MR analyses were employed to investigate a potential reverse causal association.

Results

Genetically predicted higher FT4 was not associated with the risk of BPD (OR: 1.18; P = 0.60, IVW) or the risk of SCZ (OR: 0.93; P = 0.19, IVW). Genetically predicted higher TSH was not associated with the risk of BPD (OR: 1.11; P = 0.51, IVW) or SCZ (OR: 0.98, P = 0.55, IVW). Genetically predicted hypothyroidism was not associated with BPD or SCZ. We found no evidence for a reverse causal effect between BPD or SCZ on thyroid function.

Conclusions

We report evidence for a null association between genetically predicted FT4, TSH or hypothyroidism with BPD or SCZ risk. There was no evidence for reverse causality.
Gellan residues on paper: quantification and implication for paper conservation
Authors: Henniges Ute , Brückle Irene , Khaliliyan Hajar , Böhmdorfer Stefan
Published: February 2024

Gels prepared from the polysaccharide gellan are used for aqueous poulticing treatments in paper conservation when the application of water must be restricted. Optimal use of the rigid, yet shapeable gel requires direct contact with the paper surface, which carries the risk of gel residues on the treated surface. We used acid methanolysis as a destructive analytical method to detect rhamnose as a component of gellan, which was undetectable with ATR-FTIR spectroscopy. We show that there is a significant probability of leaving gellan residues on the paper. Conservators should be aware of this potential side effect when considering the use of gellan poultices in direct contact with paper objects.
The potential of international large-scale assessments for meta-analyses in education
Authors: Scherer Ronny , Siddiq Fazilat , Nilsen Trude
Published: February 2024

Meta-analyses and international large-scale assessments (ILSA) are key sources for informing educational policy, research, and practice. While many critical research questions could be addressed by drawing evidence from both of these sources, meta-analysts seldom integrate ILSAs, and current integration practices lack methodological guidance. The aim of this methodological review is therefore to synthesize and illustrate the principles and practices of including ILSA data in meta-analyses. Specifically, we (a) review four ILSA data inclusion approaches (analytic steps, potential, challenges); (b) examine whether and how existing meta-analyses included ILSA data; and (c) provide a hands-on illustrative example of how to implement the four approaches. Seeing the need for meta-analyses on educational inequalities, we situated the review and illustration in the context of gender differences and socioeconomic gaps in student achievement. Ultimately, we outline the steps meta-analysts could take to utilize the potential and address the challenges of ILSA data for meta-analyses in education.
Delayed traumatic aortic valve perforation after blunt chest trauma
Authors: Noda Kazuki , Takahashi Yosuke , Morisaki Akimasa , Sakon Yoshito , Nishiya Kenta , Inno Goki , Nishimoto Yukihiro , Sumii Yosuke , Nagao Munehide , Shibata Toshihiko
Published: February 2024

Background

Aortic valve perforation is a rare complication of blunt chest trauma. We report a case of delayed aortic insufficiency presenting several months after trauma.

Case presentation

A 17-year-old male presented to the emergency department with traumatic brain injuries and blunt chest trauma, but no evidence of cardiac injuries. Three months later, he developed acute heart failure due to severe aortic valve regurgitation with left ventricular dysfunction. A sizable tear in the right coronary cusp caused aortic insufficiency. He was treated successfully by surgical replacement with an aortic bioprosthesis.

Conclusion

We reported a successful surgical case of valve replacement for delayed aortic valve perforation. Delayed valve perforation should be kept in mind after blunt chest trauma.
Assessment of novel electrophysiology simulator—a survey study
Authors: Koźlik Maciej , Kosiuk Jędrzej , Cogiel Michał , Kost Jan , Hemmerling Daria , Staniszewski Michał , Szczęsna Agnieszka , Wojakowski Wojciech , Jadczyk Tomasz
Published: February 2024

Background

Invasive electrophysiology (EP) training requires intellectual skills related to the interpretation of intracardiac electrograms. The classic approach to the education of young electrophysiologists focused solely on theoretical knowledge and overseen procedures in patients as no real-life-like simulation of EP studies was available.

Objective

The purpose of this study was to assess a novel tool for EP training based on fully interactive, online simulator providing real clinical experience to the users.

Methods

EP simulator users access a system with simulated electrocardiogram, mimicking signals recorded by a catheter. Assessment of EP simulator by 40 electrophysiologists from 16 countries was collected via online questionnaire.

Results

The realism of ECG signals was described as excellent or very good by 90% of responders, of intracardial signals by 82.5%. Realism of signal interactions and user experience was judged as excellent or very good by 75% and 70% accordingly. One hundred percent of users agree definitely or mostly that EP Simulator helps to translate theoretical into practical knowledge. Of responders, 97.5% would include it in EP training programs as it is extremely or very useful for training purposes in the opinion of 87.5%. Of responders, 72.5% think that training on EP simulator can potentially reduce the rate of complications. In 87.5%, the overall experience was completely or mostly satisfying and would be recommended by 100% of responders.

Conclusion

EP simulator is a feasible tool for training of young electrophysiologist, and it may be potentially included in the cardiologist curriculum. We should particularly emphasize the positive respondents’ assessment of EP simulator overall realism.
Heterorhabditis alii n. sp. (Nematoda: Heterorhabditidae), a novel entomopathogenic nematode from Egypt used against the fall armyworm, Spodoptera frugiperda (Smith 1797) (Lepidoptera: Noctuidae)
Authors: Shamseldean M. S. M. , Abo-Shady N. M. , El-Awady Mohamed. A. M. , Heikal M. N.
Published: February 2024

Background

Isolation of novel species of entomopathogenic nematodes (EPNs) with biocontrol potential against important insect pests is very important for the sustainable management of economic pests damaging food crops and providing protection to the agricultural environment. This study was aimed to new indigenous EPN isolates from Egyptian agricultural soils and studies its biocontrol potential for further use in the biological control programs. Five out of 15 soil samples obtained from a farm located at the Cairo–Alexandria desert highway was positive for the presence of EPN, using the greater wax moth baiting method.

Results

Sequencing of the internal transcribed spacer (ITS) region of 4 of the nematode isolates suggested that they belong to the species Heterorhabditis indica. However, one isolate does not show a high similarity to any of the H. indica previously recorded in the database of the Gen Bank and hence was identified as a new Heterorhabditis species and was deposited at the National Center for Biotechnology Information (NCBI) and registered under accession no. (OP555450) under the name of Heterorhabditis alii. This new species was also registered in the ZooBank under the registration link of: LSID urn: lsid: zoobank.org: act: 306F9D57-CC30-4B8E-8B19-4F0E42B08F34. No males were found in this species. Morphological characterization using the light microscope (LM) and scanning electron microscope (SEM) confirmed the identification of this nematode as a new species of the genus Heterorhabditis. Moreover, virulence of this new species against the fall armyworm (FAW), Spodoptera frugiperda (Smith 1797) (Lepidoptera: Noctuidae) was tested in comparison with the foreign EPN species, Heterorhabditis bacteriophora (HP88) and the local Heterorhabditis indica (Mango 2 isolate) and proved to be more effective against this devastative insect pest than the two compared species.

Conclusions

The present study found out a new species of the EPN genus, Heterorhabditis in Egypt. Our results were confirmed by both morphological and molecular analyses. The efficacy of this new species against the FAW proved to be a potent and safe biocontrol agent that can be used in biological control programs against this invasive insect pest of corn in Egypt and other global countries.
Value of MUNE versus compound muscle action potential in assessing motor unit loss in patients with carpal tunnel syndrome
Authors: Abdul-Muneem Safa Dheaa Al-Den , Kaddoori Hussein Ghani
Published: February 2024

Background

The most prevalent nerve entrapment disorder, known as carpal tunnel syndrome (CTS), is brought on by wrist-based median nerve compression. Focal demyelination progresses to axonal dysfunction as the condition worsens. In order to detect motor unit (MU) loos, this study compares two motor unit number estimation (MUNE) techniques with compound muscle action potential (CMAP) amplitude. The CMAP amplitude and MUNE of the median nerve in 137 hands of 70 neurophysiologically approved CTS patients, aged 40.27 ± 10.06 years were examined. Another 90 hands from 56 healthy volunteers who are age- and gender-matched serve the control group.

Results

In contrast to 192.5 and 248.5 in controls, the median nerve values of incremental and adapted multipoint stimulation (aMPS) MUNE in CTS patients were, respectively, 111 and 133 (p < 0.0001). Patients with severe CTS compared to those with mild CTS using both methods had significantly lower MUNE. MUNE values are the same regardless of gender or hand dominance. In comparison to MUNE methods (cutoff values of 106.5 and 203, respectively), CMAP amplitude had a sensitivity and specificity of more than 60% in detecting MU loss (cutoff value of 6.85 mV). The CTS grading had no effect on the CMAP amplitude. MUNE values had positive with CMAP amplitude and negative with CTS grading and Phalen test positivity.

Conclusions

When identifying motor nerve involvement in CTS patients, the MUNE technique is more accurate than a standard motor nerve conduction study (NCS). It was emphasized that MUNE evaluation in determining MU loss in the early stages of CTS may be helpful in diagnosis and treatment. There was no correlation between handedness and the number of MUs as determined by MUNE techniques. Both methods almost equally identify MU loss and have the same sensitivity and specificity.
Reframing sustainability initiatives in higher education
Authors: Husic Diane White
Published: February 2024

Amidst the ever-changing and increasingly complex challenges facing the planet and humanity, there is a growing need to educate the next generation of environmental stewards and leaders who are global citizens with sustainability mindsets. Universities have come a long way in developing sustainability programs – both in the curriculum and in terms of campus operations. Many research universities are highly focused on cutting-edge science and technology to address global challenges, and funders are looking for that innovation and entrepreneurialism. These are noteworthy efforts, but do they give students what they need or want? Has the commercialization and corporatization of college campuses led to a shift away from the notion that higher education is a public good that benefits society, not just individuals? Beyond the technical expertise, 21st century challenges demand that the workforce be diverse and capable of recognizing and tackling ethical, cultural, and equity issues for a sustainable and just future. An ethics-driven and interdisciplinarity curriculum framed around the Sustainable Development Goals (SDG), civic engagement, and experiential learning that allows students to put their knowledge into action is needed to prepare individuals for such a workforce. This paper provides both a critique of areas in which higher education is falling short of its responsibilities and some translatable models and opportunities for improvements in reframing sustainability initiatives on campus, including in the curriculum.

Policy and Practice Recommendations

• Campus leaders and faculty should take note of surveys of younger generations, especially Gen Z and Gen alpha, as they provide valuable insights into what youth are focused on and what knowledge and set of skills they desire to become innovative problem solvers and builders of more resilient communities.

• To prepare the next generation of environmental stewards and leaders, high impact practices that move knowledge to action are needed.

• Sustainability topics should be incorporated across the curriculum on campuses, not just in certain majors.

• Higher education needs to re-embrace the notion of service to the public good and work collaboratively across institutions and sectors to address complex societal challenges.
Teacher candidates’ views of future SSI instruction: a multiple case study
Authors: Kinskey Melanie , Newton Mark
Published: February 2024

The instructional approach of incorporating socioscientific issues (SSI) into science teaching has been found to improve critical thinking and problem-solving skills among K-12 students. Preparation for how to facilitate SSI in the classroom, however, is limited, resulting in very few classrooms across the United States providing opportunities for K-12 students to grapple with these real-world problems. In this manuscript we compare the integration of socioscientific issues (SSI) within two different undergraduate course contexts: a science methods course that is part of an elementary educator preparation program and a science content course designed for secondary future educators. Through this comparison we aim to provide science education researchers and science teacher educators with empirical support related to how the delivery of SSI influences elementary to secondary teacher candidates’ views of SSI as they relate to student engagement, teacher effectiveness, and curricula. Leveraging a mixed methods case study approach, data from each course context were collected through Likert-type surveys and open-ended responses. Findings suggest exposure to SSI pedagogies in science methods and content courses influence teacher candidates’ views in different ways and we must consider field and course-based work occurring simultaneously while teacher candidates are learning about SSI-based instruction. Implications for this are discussed.
An atypical presentation of ulcerative colitis: case report
Authors: Saoji Avanti , Kavishwar Madhura , Unki Praveen , Rathi Surbhi
Published: February 2024

Background

Bloody diarrhea in children often indicates a severe gastrointestinal illness. Although infections are the most likely cause, inflammatory bowel disease (IBD) is a close mimic. IBD generally presents with chronic and persistent symptoms requiring long-term treatment. Hence, acute or atypical presentations may mislead the physician leading to delays in diagnosis. We report the case of an atypical presentation of ulcerative colitis.

Case presentation

We present the case of a 6-year-old girl with acute symptoms of bloody diarrhea, fever, abdominal pain, and tenesmus for 5 days. The child came to us after the non-resolution of symptoms after treatment from a local practitioner. The child was found to have signs of chronic malnutrition and clubbing on general examination. After ruling out infective causes, the child was evaluated further by colonoscopy, which revealed lesions suggestive of ulcerative colitis, and hence started on topical and oral treatment for the same.

Conclusion

Awareness about the disease and its atypical presentations like poor growth, anemia, or extraintestinal manifestations is necessary, especially in primary healthcare and resource-poor settings as it can lead to early diagnosis, referral, and treatment initiation.
Gamification in physiotherapy and rehabilitation education: a narrative review
Authors: Dereli Muge , Kahraman Turhan
Published: February 2024

Background

For learning activities that commence and continue with the effect of motivation, novel and entertaining learning methods are developed by considering needs. As a result of the student-centered learning approach gaining importance, gamification has emerged that transfer game components to subjects. Gamification in education health professions improves students’ knowledge levels and clinical skills. Therefore, gamification techniques are integrated into physiotherapy education. This review aims to examine the effects of gamification techniques in physiotherapy and rehabilitation education.

Educational escape rooms reinforce academic achievement by enabling students to use their problem-solving skills in subjects; it provides the evaluation of practical skills by reducing anxiety and stress levels of physiotherapy students in exams. Educational board games motivate physiotherapy students, facilitate recall of information, and increase academic achievement. Online quizzes encourage physiotherapy students to study day to day in their subjects, increasing their achievement and participation in subjects. Gamified websites and gamified physiotherapy case studies motivate students, while virtual reality-based games used in practice subjects facilitate the learning process.
Development of a new design methodology for slab track systems
Authors: Aly Mohamed Hafez , Elnaga Islam Mahmoud Abou , Soliman Ahmed Abdul Hay , Diab Muhammad Ahmad
Published: February 2024

Owing to the rapid increase in the demands of train speed and axle loads, the slab track has been introduced to replace the ballast in the classical ballasted track with reinforced concrete slab or asphalt-bearing layer to improve the track stability, strength, and durability. This paper aims to develop a new methodology for estimating the rail deformations for the most common slab track systems (BÖGL, Shinkansen, and RHEDA 2000. This methodology yielded the first design aid for slab track systems based on design equations and graphs for high-speed systems. Using a regression analysis of more than 300 finite element models which are validated by experimental tests, the relationship between the rail deflection, modulus of elasticity for subgrade and replacement, and the replacement thickness was determined for the most common slab tracks under the American (AREMA) and European (EN) loads. According to EN, it was found that the minimum modulus of elasticity for subgrade to fulfill the rail deflection criterion without a replacement soil ranges from 128 to 143 MPa for the most common slab track systems; meanwhile, for AREMA, it ranges from 59 to 70 MPa. Furthermore, for these slab track systems, one simple design chart was introduced to aid engineers with the design of the slab track replacement layer according to each design code.
Pharmaceutical Industry Payments to Medical Oncologists in the Netherlands: Trends and Patterns Provided by an Open-Access Transparency Data Set
Authors: Schnog J.B. , Samson M.J. , Gersenbluth I. , Duits A.J.
Published: February 2024

PURPOSE

Health care expenditure related to oncologic treatments is skyrocketing although many treatments offer marginal, if any, clinical benefit. Financial conflicts of interest (fCOI) resulting from pharmaceutical industry (pharma) payments to physicians is increasingly recognized as a predictive factor for regulatory board approval and guideline incorporation of low-value treatments. We sought to study the extent to which pharma payments to medical oncologists occur in the Netherlands, the amount of money involved, and whether these occur more frequently and are higher for key opinion leaders (KOLs).

METHODS

In our cross-sectional retrospective database study, we used several Dutch open-access databases and extracted data registered between 2019 and 2021.

RESULTS

A cumulative amount of €899,863 was paid to 48.8% of the 408 registered medical oncologists. Over time, there was a marked decline in both the proportion of medical oncologists receiving payments (from 40.4% in 2019 to 19.1% in 2021) and the mean annual value of payments (from €2,962 in 2019 to €2,188 in 2021) with the latter mainly resulting from a decline in hospitality-related transactions. KOLs were more likely to receive industry payments and received a higher median payment value.

DISCUSSION

Our findings should contribute to the increasing awareness in the Netherlands of the potential effects of fCOI.
Challenges and Solutions to Support Oncology Professionals Serving Underserved Populations With Cancer in the United States: Results From the ASCO Serving the Underserved Task Force
Authors: Patel Manali I. , Hinyard Leslie , Merrill Janette K. , Smith Kimberly T. , Lei Jennifer , Carrizosa Daniel , Kamaraju Sailaja , Hlubocky Fay J. , Kalwar Tricia , Fashoyin-Aje Lola , Gomez Scarlett L. , Jeames Sanford , Florez Narjust , Kircher Sheetal M. , Tap William D.
Published: February 2024

PURPOSE

Little data exist regarding approaches to support oncology professionals who deliver cancer care for underserved populations. In response, ASCO developed the Serving the Underserved Task Force to learn from and support oncology professionals serving underserved populations.

METHODS

The Task Force developed a 28-question survey to assess oncology professionals' experiences and strategies to support their work caring for underserved populations. The survey was deployed via an online link to 600 oncology professionals and assessed respondent and patient demographic characteristics, clinic-based processes to coordinate health-related social services, and strategies for professional society support and engagement. We used chi-square tests to evaluate whether there were associations between percent full-time equivalent (FTE) effort serving underserved populations (<50% FTE v ≥50% FTE) with responses.

RESULTS

Of 462 respondents who completed the survey (77% response rate), 79 (17.1%) were Asian; 30 (6.5%) Black; 43 (9.3%) Hispanic or Latino/Latina; and 277 (60%) White. The majority (n = 366, 79.2%) had a medical doctor degree (MD). A total of 174 (37.7%) had <25% FTE, 151 (32.7%) had 25%-50% FTE, and 121 (26.2%) had ≥50% FTE effort serving underserved populations. Most best guessed patients' sociodemographic characteristics (n = 388; 84%), while 42 (9.2%) used data collected by the clinic. Social workers coordinated most health-related social services. However, in clinical settings with high proportions of underserved patients, there was greater reliance on nonclinical personnel, such as navigators (odds ratio [OR], 2.15 [95% CI, 1.07 to 4.33]) or no individual (OR, 2.55 [95% CI, 1.14 to 5.72]) for addressing mental health needs and greater reliance on physicians or advance practice practitioners (OR, 2.54 [95% CI, 1.11 to 5.81]) or no individual (OR, 1.91 [95% CI, 1.09 to 3.35]) for addressing childcare or eldercare needs compared with social workers. Prioritization of solutions, which did not differ by FTE effort serving underserved populations, included a return-on-investment model to support personnel, integrated health-related social needs screening, and collaboration with the professional society on advocacy and policy.

CONCLUSION

The findings highlight crucial strategies that professional societies can implement to support oncology clinicians serving underserved populations with cancer.
Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer
Authors: Saylor Philip J. , Otani Keisuke , Balza Rene , Ukleja Jacob , Pleskow Haley , Fisher Rebecca , Kusaka Erika , Otani Yukako S. , Badusi Priscilla Oluwakemi , Smith Matthew R. , Meneely Erika , Olivier Kara , Lowe Alarice C. , Toner Mehmet , Maheswaran Shyamala , Haber Daniel A. , Yeap Beow Y. , Lee Richard J. , Miyamoto David T.
Published: February 2024

PURPOSE

Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity.

PATIENTS AND METHODS

Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer–specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction.

RESULTS

The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS ( P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase.

CONCLUSION

Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.
Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation—Where Are We Now?
Authors: Patil Hemlata , Vemula Sateesh Kumar , Narala Sagar , Lakkala Preethi , Munnangi Siva Ram , Narala Nagarjuna , Jara Miguel O. , Williams Robert O. , Terefe Hibreniguss , Repka Michael A.
Published: February 2024

Hot-melt extrusion (HME) is a globally recognized, robust, effective technology that enhances the bioavailability of poorly soluble active pharmaceutical ingredients and offers an efficient continuous manufacturing process. The twin-screw extruder (TSE) offers an extremely resourceful customizable mixer that is used for continuous compounding and granulation by using different combinations of conveying elements, kneading elements (forward and reverse configuration), and distributive mixing elements. TSE is thus efficiently utilized for dry, wet, or melt granulation not only to manufacture dosage forms such as tablets, capsules, or granule-filled sachets, but also for designing novel formulations such as dry powder inhalers, drying units for granules, nanoextrusion, 3D printing, complexation, and amorphous solid dispersions. Over the past decades, combined academic and pharmaceutical industry collaborations have driven novel innovations for HME technology, which has resulted in a substantial increase in published articles and patents. This article summarizes the challenges and models for executing HME scale-up. Additionally, it covers the benefits of continuous manufacturing, process analytical technology (PAT) considerations, and regulatory requirements. In summary, this well-designed review builds upon our earlier publication, probing deeper into the potential of twin-screw extruders (TSE) for various new applications.

Graphical Abstract
Effect of a critical magnetic field on the control of scalar neutral boson pair production in the context of Lorentz-symmetry violation
Authors: Jirón Andrés G. , Obispo Angel E. , Espinoza Loayza J. D. , Quispe Juan Carlos , Castro L. B.
Published: February 2024

This study investigates the production of neutral scalar boson pairs in static electromagnetic fields resulting from Lorentz-symmetry violation (LSV), with a focus on the parity-even sector of the CPT-even photon sector in the Standard Model Extension (SME). Utilizing a cross-configuration involving inhomogeneous static electric fields and homogeneous static magnetic fields, the analysis of the probability of bosons pair production identifies three different regimes determined by a critical magnetic field. Below the critical value, creation is exponentially suppressed; at the critical value, the number density of created bosons remains constant, and above the critical field, there is exponential amplification. This behavior prompts an additional investigation using von Neumann entanglement entropy to analyze fluctuations in the bosonic vacuum.
Quasi-exactly solvable potentials in Wigner-Dunkl quantum mechanics
Authors: Quesne C.
Published: February 2024

It is shown that the Dunkl harmonic oscillator on the line can be generalized to a quasi-exactly solvable one, which is an anharmonic oscillator with

known eigenstates for any

. It is also proved that the Hamiltonian of the latter can also be rewritten in a simpler way in terms of an extended Dunkl derivative. Furthermore, the Dunkl isotropic oscillator and Dunkl Coulomb potentials in the plane are generalized to quasi-exactly solvable ones. In the former case, potentials with

known eigenstates are obtained, whereas, in the latter, sets of

potentials associated with a given energy are derived.
Sirt3 Regulates Proliferation and Progesterone Production in Leydig Cells via Suppression of Reactive Oxygen Species
Authors: Matoba Hisanori , Fujii Chifumi , Maruyama Kazuaki , Kawakubo Masatomo , Momose Masanobu , Sano Kenji , Imamura Hitomi , Kurihara Hiroki , Nakayama Jun
Published: February 2024

Sirt3 is a mitochondrial protein deacetylase functioning in energy metabolism, regulation of intracellular reactive oxygen species (ROS) levels, and aging. Although Sirt3 loss has negative effects on fertility of oocytes during in vitro fertilization and on progesterone production in granulosa cells, Sirt3's function in Leydig cells remains unclear. Therefore, we investigated Sirt3 activity in Leydig cells, focusing on androgen production. To do so, we performed immunohistochemistry to confirm Sirt3 localization in gonads and observed strong Sirt3 immunostaining in Leydig cells of human testes and of Sirt3+/+ and Sirt3+/− mouse testes, while Sirt3−/− mouse testis tissue was negative. In human ovary, hilus cells were strongly Sirt3-positive, theca cells showed weak positivity, and granulosa cells showed very weak or almost no immunostaining. Next, we used the murine Leydig tumor cell line MA-10 as a model. We overexpressed Sirt3 but observed no changes in proliferation, expression of Star, Cyp11a1 (p450scc gene), and Hsd3b, or progesterone production in MA-10 cells. Sirt3 knockdown significantly reduced proliferation, suppressed expressions of steroidogenic enzymes and of transcription factors Ad4bp (Sf-1 gene) and Gata4, and decreased progesterone production. Sirt3 knockdown in MA-10 cells also increased intracellular ROS levels based on CM-H2DCFDA fluorescence dye analysis and increased the proportion of both early and late apoptotic (necrotic) cells based on Annexin V/7AAD assays. These results indicate that Sirt3 has a potential function in androgen production in Leydig cells by regulating intracellular ROS levels.
Carotid Endarterectomy With Shunt—A Stepwise Surgical Technique Demonstration for Trainees: 2-Dimensional Operative Video
Authors: Matsuo Satoshi , Kurogi Ryota , Hasegawa Toru , Yoshida Hidenori , Fujii Kiyotaka
Published: February 2024

Carotid endarterectomy (CEA) is a common cerebrovascular surgery and is an effective treatment option for patients with carotid stenosis.
1-4
Although the routine or selective use of a shunt is still debatable,
5
the CEA technique is generally well-established. We believe that bloodless and “shallow and wide” operative fields make CEA safe and successful. Maintaining a bloodless operative field is highly crucial to prevent postoperative cervical hematoma and damage to anatomic structures, such as the hypoglossal and vagus nerves, because it facilitates their identification. In the cases of CEA, antiplatelet medications are usually continued, and systemic heparinization is performed intraoperatively; therefore, further meticulous hemostasis should be performed than in other neurological surgery cases. The 2-step pull-up technique, which involves pulling up loose connective tissue surrounding the carotid arteries in addition to the carotid sheath, makes the operative field “shallow and wide.” This technique allows the internal carotid artery to move from deep to superficial, making CEA feasible, particularly when placing a shunt. This video illustrates the CEA technique used for symptomatic mild carotid stenosis in a 66-year-old man with vulnerable plaques. Evolving carotid artery stenting should facilitate the improvement of the operative technique to increase the safety and accordingly train young surgeons. This video is intended to increase familiarity with CEA because carotid artery stenting decreases CEA indications for carotid stenosis and diminishes proficiency in managing CEA. The patient consented to the publication of his image. Patient consent was obtained to perform the surgery and publish the surgical video.
Mother-Daughter Ventricular Endoscopy: A Technical Note and 2-Dimensional Video
Authors: Koueik Joyce , Sivan Vivek , Chebel Roy , Peek Michael , Iskandar Bermans J.
Published: February 2024

BACKGROUND AND IMPORTANCE:

While navigating the ventricles with a rigid endoscope provides excellent visualization and the ability to use endoscopic instruments for complex surgery, these endoscopes are often too large to navigate tight areas. We present a surgical video showing the technique of mother-daughter endoscopy, which consists of the introduction of a flexible 1-mm fiberoptic endoscope through the channel of a large rigid endoscope to allow visualization across small spaces or channels, in this case, the cerebral aqueduct. This combination of superior visualization and handling of rigid endoscopes and flexibility and small size of fiberoptic endoscopes enhances safety and broadens possibilities in ventricular surgery.

CLINICAL PRESENTATION:

A 64-year-old woman with prior endoscopic aqueductoplasty for triventricular hydrocephalus and a failed endoscopic third ventriculostomy presented with focal restenosis of the aqueduct. A repeat endoscopic aqueductoplasty with stent placement were performed. Mother-daughter endoscopy was used to explore the occluded aqueduct for improved safety before fenestration and to ensure proper stent placement after fenestration.

CONCLUSION:

Mother-daughter endoscopy can add safety to complex or high-risk endoscopic procedures, particularly those with tight spaces that the large mother endoscope cannot visualize.
Hibernating female big brown bats (Eptesicus fuscus) adjust huddling and drinking behaviour, but not arousal frequency, in response to low humidity
Authors: Muise Kristina A. , Dzal Yvonne A. , Fletcher Quinn E. , Willis Craig K. R.
Published: February 2024

Many mammals hibernate during winter, reducing energy expenditure via bouts of torpor. The majority of a hibernator's energy reserves are used to fuel brief, but costly, arousals from torpor. Although arousals likely serve multiple functions, an important one is to restore water stores depleted during torpor. Many hibernating bat species require high humidity, presumably to reduce torpid water loss, but big brown bats (Eptesicus fuscus) appear tolerant of a wide humidity range. We tested the hypothesis that hibernating female E. fuscus use behavioural flexibility during torpor and arousals to maintain water balance and reduce energy expenditure. We predicted: (1) E. fuscus hibernating in dry conditions would exhibit more compact huddles during torpor and drink more frequently than bats in high humidity conditions; and (2) the frequency and duration of torpor bouts and arousals, and thus total loss of body mass would not differ between bats in the two environments. We housed hibernating E. fuscus in temperature- and humidity-controlled incubators at 50% or 98% relative humidity (8°C, 110 days). Bats in the dry environment maintained a more compact huddle during torpor and drank more frequently during arousals. Bats in the two environments had a similar number of arousals, but arousal duration was shorter in the dry environment. However, total loss of body mass over hibernation did not differ between treatments, indicating that the two groups used similar amounts of energy. Our results suggest that behavioural flexibility allows hibernating E. fuscus to maintain water balance and reduce energy costs across a wide range of hibernation humidities.
The Frequency of Dedicated Coursework in Behavior Change in Accredited Baccalaureate Exercise Science Programs
Authors: Stapleton Drue T. , Kerner Lauren , Guers John J.
Published: February 2024

Introduction/Purpose

Despite the well-established benefits of physical activity (PA), low levels of participation in PA remain a concern. Professional programmatic standards including behavior modification techniques are outlined by the Commission on Accreditation of Allied Health Education Programs (CAAHEP) and the Commission on the Accreditation of Exercise Science (CoAES), but it is not clear how these competencies are being met. Given the complexities of PA behavior, dedicated coursework addressing the fundamentals of behavior modification is valuable. The purpose of this study was to examine the prevalence of dedicated coursework focused on behavior change in CAAHEP/CoAES-accredited baccalaureate exercise science (EXS) programs.

Methods

We searched the curricula of CAAHEP/CoAES-accredited baccalaureate EXS programs to determine if dedicated behavior modification courses were required. We organized programs by American College of Sports Medicine region and Carnegie Classification.

Results

Of the 65 accredited programs found, 19 (29%) had specific courses in behavior modification. Of these 19 programs, New England (57%) and Northland (50%) regions had the highest percentage of required coursework. Carnegie master’s colleges and universities had the highest percentage of programs containing dedicated courses on behavior change (42%), compared with baccalaureate colleges (21%) and doctoral universities (37%).

Conclusions

Despite established educational competencies, many accredited EXS programs do not include dedicated coursework in behavior modification. Although CAAHEP/CoAES accreditation standards include behavior modification competencies, to maximize the benefits of PA and exercise and prepare the next generation of exercise professionals, dedicated coursework in behavior change should be incorporated into EXS curricula.
Αποτίμηση σεισμικής τρωτότητας μνημειακών κατασκευών
Authors: Καφετζή Παρασκευή
Published: February 2024

Απώτερος στόχος της υπό εκπόνηση διδακτορικής διατριβής με τίτλο «Αποτίμηση σεισμικής τρωτότητας μνημειακών κατασκευών» είναι η προαγωγή γνώσης σχετικά με το θέμα της αντισεισμικής προστασίας μνημειακών κατασκευών, μέσω χρήσης σύγχρονων υπολογιστικών μεθόδων. Ειδικότερα, πρόκειται να διερευνηθούν συνιστώσες πολλαπλής διακινδύνευσης μνημειακών κατασκευών, οι οποίες υποβάλλονται σε σεισμικές δράσεις σε συνδυασμό με την επιρροή περιβαλλοντικών παραμέτρων, διασφαλίζοντας την προστασία των μνημειακών αξιών. Κατά την αποτίμηση της σεισμικής τρωτότητας ιστορικών κτιρίων από άοπλη φέρουσα τοιχοποιία, αξιοποιούνται καμπύλες τρωτότητας, οι οποίες περιγράφουν τον αναμενόμενο βαθμό βλάβης για δεδομένη σεισμική δράση και συγκεκριμένη χρονική στιγμή, στην οποία και εκτιμώνται οι μηχανικές ιδιότητες των υλικών. Ωστόσο, λόγω συνθηκών γήρανσης τα μηχανικά χαρακτηριστικά της φέρουσας τοιχοποιίας υποβαθμίζονται εν τω χρόνω, δεδομένης της μακράς διάρκειας ζωής των μνημειακών κατασκευών σε σχέση με τις συμβατικές. Ως εκ τούτου, στην παρούσα διατριβή αναπτύσσεται μεθοδολογία για την αποτίμηση της σεισμικής τρωτότητας ιστορικών κτιρίων, συνεκτιμώντας διεργασίες φθοράς και γήρανσης της άοπλης φέρουσας τοιχοποιίας. Η μεθοδολογία αποτίμησης της σεισμικής τρωτότητας εφαρμόζεται στην περίπτωση ενός συνήθους τυπολογικά ιστορικού κτιρίου, λαμβάνοντας υπόψη την επιρροή του χρόνου στην απομείωση μηχανικών και παραμορφωσιακών χαρακτηριστικών της άοπλης φέρουσας τοιχοποιίας. Στα πλαίσια της μεθοδολογίας προτείνονται σχέσεις υποβάθμισης των μηχανικών χαρακτηριστικών συναρτήσει του χρόνου και διεξάγονται ανελαστικές δυναμικές αναλύσεις για ακολουθία σεισμικών διεγέρσεων κλιμακούμενων σε πολλαπλές εντάσεις και σε διάφορες ηλικίες του ιστορικού κτιρίου. Με βάση τα αποτελέσματα των σεισμικών αναλύσεων, χαράσσονται καμπύλες τρωτότητας, συνεκτιμώντας τις υπεισερχόμενες αβεβαιότητες. Μέσω των καμπυλών εκφράζεται η αυξανόμενη στο χρόνο τρωτότητα του ιστορικού κτιρίου λόγω των μηχανισμών φθοράς και γήρανσης. Οι καμπύλες τρωτότητας, οι οποίες προκύπτουν από την παρούσα διδακτορική διατριβή μπορούν να ενσωματωθούν στην εκτίμηση της σεισμικής διακινδύνευσης του πολιτιστικού αποθέματος.
current possible treatment approaches of Polycystic Ovary Syndrome (PCOS)
Authors: Lipińska Justyna , Kowalczuk Maria , Lipiński Łukasz , Kopeć Izabela , Kamiński Jakub , Klimczak Klaudia , Loryś Laura , Narloch Marcin , Kasprzak Stanisław , Kasprzak Karolina
Published: February 2024

Introduction

            Polycystic ovary syndrome (PCOS), first described by Stein and Leventhal in 1935, is one of the most prevalent endocrine system conditions affecting women of reproductive age. It affects between 6% and 13% of women and the majority of cases are identified between the ages of 20 and 30. Unfortunately, the disease is usually diagnosed only when bothersome symptoms such as hair loss, alopecia, acne, and infertility-related problems occur. Based on the Rotterdam criteria, four phenotypes of PCOS are distinguished.

Aim of the study

            This review aims to present the current state of knowledge about possible treatment approaches, both non-pharmacological and pharmacological.

Materials and methods

           The paper was created based on the Pubmed database. The literature was reviewed using the keywords: ”PCOS”, ”PCOS treatment” and “ PCOS medications “.

The current state of knowledge

          Treatments for PCOS must be tailored to the specific needs of each patient. In the management of PCOS, special attention is paid to diet, physical activity, and restoration of the Gut Microbiome. Medications used in therapy are oral contraceptives and anti-androgens, insulin sensitizers, ovulation inducers, calcium and vitamin D supplements, statins, Glucagon-like-peptide-1 (GLP-1) agonists, inositols and interleukin 22 (IL-22)  therapy.

Summary

           Treatment options for menstrual irregularities and hirsutism are based on the clinical goals and preferences of the patient. The ideal would be causal treatment, but due to the ongoing lack of full understanding of the pathogenesis of the syndrome, is not entirely feasible. The ideal would be causal treatment, but due to the ongoing lack of full understanding of the pathogenesis of the syndrome, is not entirely feasible. The most important is a multimodal approach to treat comorbid conditions such as diabetes mellitus type 2, obesity, hyperlipidemia, depression, and infertility.