bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definitive carbon ion re-irradiation with pencil beam scanning in the treatment of unresectable locally recurrent rectal cancer
Authors: Cai Xin , Li Ping , Zhao Jingfang , Wang Weiwei , Cheng Jingyi , Zhang Guangyuan , Cai Sanjun , Zhang Zhen , Jiang Guoliang , Zhang Qing , Wang Zheng 
Published: September 2023

Abstract
This study aimed to evaluate the oncological outcomes and safety of carbon ion re-irradiation with pencil beam scanning (PBS) delivery technique for previously irradiated and unresectable locally recurrent rectal cancer (LRRC). Between June 2017 and September 2021, 24 patients of unresectable LRRC with prior pelvic photon radiotherapy who underwent carbon ion re-irradiation at our institute were retrospectively analyzed. Carbon ion radiotherapy was delivered by raster scanning with a median relative biological effectiveness-weighted dose of 72 Gy in 20 fractions. Weekly CT reviews were carried out, and offline adaptive replanning was performed whenever required. The median follow-up duration was 23.8 months (range, 6.2–47.1 months). At the last follow-up, two patients had a local disease progression, and 11 patients developed distant metastases. The 1- and 2-year local control, progression-free survival and overall survival rates were 100 and 93.3%, 70.8 and 45.0% and 86.7 and 81.3%, respectively. There were no Grade 3 or higher acute toxicities observed. Three patients developed Grade 3 late toxicities, one each with gastrointestinal toxicity, skin reaction and pelvic infection. In conclusion, definitive carbon ion re-irradiation with PBS provided superior oncologic results with tolerable toxicities and may be served as a curative treatment strategy in unresectable LRRC.
Histo-morphological Characterization of the Tongue and Oropharyngeal Cavity of the Shining Sunbird (Cinnyris habessinicus)
Authors: El-Mansi Ahmed A , Al-Kahtani Mohamed A , Alshahrani Hend , Ibrahim Esam H , Al-Doaiss Amin , Abd-Elhafeez Hanan H , Soliman Soha A , Taha Ramadan , ElBealy Eman 
Published: September 2023

AbstractSunbirds, as specialized nectarivores, have developed multiple lingual and oropharyngeal peculiarities imposed by this dietary specialization that particularly extract floral nectar. We have described the functional morphology of the tongues and palates of the shining sunbird, Cinnyris habessinicus, using gross anatomical, histological, and scanning electron microscopic methods. The tongue was bifurcated with fringed lamella and extended posteriorly, forming a broad trough at the lingual body and terminating in two fleshy, alae linguae. The lingual apex and body are nonpapillate and nonglandular, and its root had a muscular pad followed by a conspicuous laryngeal mound bordered by three prominent rows of conical papillae. The lingual root had clusters of mucoid glands with rich acidic mucins, and the laryngeal region had complex papillary distribution at the back margins. Both the lingual body and root had well-developed skeletal elements, musculature, and connective tissues. Furthermore, the palate was membranous and made up of four main ridges with a central choanal slit guarded by choanal papillae. Overall, the presented results showed structural and anatomical features that are the results of the nectarivory dietary niche.
Changes in Rat Adrenal Cortex and Pineal Gland in Inverted Light–Dark Cycle: A Biochemical, Histological, and Immunohistochemical Study
Authors: Shawky Heba A , Abdel Hafez Sara Mohamed Naguib , Hasan Nabil Abdel Kader , Elbassuoni Eman , Abdelbaky Fatma Alzhraa Fouad , AboBakr Abdel Hamid Sayed 
Published: September 2023

AbstractPoor sleep standards are common in everyday life; it is frequently linked to a rise in stress levels. The adrenal gland interacts physiologically with the pineal gland in the stress response. Pineal gland is a small endocrine organ that modulates sleep patterns. This work aimed to evaluate the inverted light–dark cycle rhythm on the histological changes within the adrenal cortex and pineal gland in adult male albino rats. Twenty adult male albino rats were equally divided into two groups: For the first control group, animals were kept on daylight–darkness for 12–12 h. The second group was kept under an inverted 12- to 12-h light–darkness cycle for 4 weeks. Adrenal sections were subjected to biochemical, histological, and immunohistochemical study. Inverted light–dark cycle group recorded a significant elevation of plasma corticosterone, tissue malondialdehyde, tumor necrosis factor-α, and interleukin-1β (IL-1β) associated with a significant reduction of catalase and superoxide dismutase. Adrenal cortex showed biochemical and histological changes. Pineal glands also showed loss of lobular architecture. A significant upregulation in activated inducible nitric oxide synthase (iNOS) and B-cell lymphoma-associated X (Bax) immunohistochemical expression was recorded in adrenal cortex associating with downregulation in B-cell lymphoma 2 (Bcl-2). It could be concluded that subchronic inverted light–dark cycle exerted direct effects on adrenal cortex and the pineal glands.
Teaching Clinical Reasoning in the Preclinical Period
Authors: Mallory Renee , Maciuba Joseph M , Roy Michael , Durning Steven J 
Published: September 2023

ABSTRACT

Introduction
Developing the clinical reasoning skills necessary to becoming an astute diagnostician is essential for medical students. While some medical schools offer longitudinal opportunities for students to practice clinical reasoning during the preclinical curriculum, there remains a paucity of literature fully describing what that curriculum looks like. As a result, medical educators struggle to know what an effective clinical reasoning curriculum should look like, how it should be delivered, how it should be assessed, or what faculty development is necessary to be successful. We present our Introduction to Clinical Reasoning course that is offered throughout the preclinical curriculum of the Uniformed Services University of the Health Sciences. The course introduces clinical reasoning through interactive lectures and 28 case-based small group activities over 15 months.
The curriculum is grounded in script theory with a focus on diagnostic reasoning. Specific emphasis is placed on building the student’s semantic competence, constructing problem lists, comparing and contrasting similar diagnoses, constructing a summary statement, and formulating a prioritized differential diagnosis the student can defend. Several complementary methods of assessment are utilized across the curriculum. These include assessments of participation, knowledge, and application. The course leverages clinical faculty, graduate medical education trainees, and senior medical students as small group facilitators. Feedback from students and faculty consistently identifies the course as a highly effective and engaging way to teach clinical reasoning.

Conclusion
Our Introduction to Clinical Reasoning course offers students repeated exposure to well-selected cases to promote their development of clinical reasoning. The course is an example of how clinical reasoning can be taught across the preclinical curriculum without extensive faculty training in medical education or clinical reasoning theory. The course can be adapted into different instructional formats to cover a variety of topics to provide the early learner with sequential exposure and practice in diagnostic reasoning.
Fallback onto kicked neutron stars and its effect on spin-kick alignment
Authors: Müller Bernhard 
Published: September 2023

ABSTRACT
Fallback in core-collapse supernova explosions is potentially of significant importance for the birth spins of neutron stars and black holes. It has recently been pointed out that the angular momentum imparted onto a compact remnant by fallback material is subtly intertwined with its kick because fallback onto a moving neutron star or black hole will preferentially come for a conical region around its direction of travel. We show that contrary to earlier expectations such one-sided fallback accretion onto a neutron star will tend to produce spin-kick misalignment. Since the baroclinic driving term in the vorticity equation is perpendicular to the nearly radial pressure gradient, convective eddies in the progenitor as well as Rayleigh–Taylor plumes growing during the explosion primarily carry angular momentum perpendicular to the radial direction. Fallback material from the accretion volume of a moving neutron star therefore carries substantial angular momentum perpendicular to the kick velocity. We estimate the seed angular momentum fluctuations from convective motions in core-collapse supernova progenitors and argue that accreted fallback material will almost invariably be accreted with the maximum permissible specific angular momentum for reaching the Alfvén radius. This imposes a limit of ${\sim }10^{-2}\, \mathrm{M}_\odot$ of fallback accretion for fast-spinning young neutron stars with periods of ${\sim }20\, \mathrm{ms}$ and less for longer birth spin periods.
Past the outer rim, into the unknown: structures beyond the Kuiper Cliff
Authors: de la Fuente Marcos C , de la Fuente Marcos R 
Published: September 2023

ABSTRACT
Although the present-day orbital distribution of minor bodies that go around the Sun between the orbit of Neptune and the Kuiper Cliff is well understood, past ∼50 au from the Sun, our vision gets blurred as objects become fainter and fainter and their orbital periods span several centuries. Deep imaging using the largest telescopes can overcome the first issue but the problems derived from the second one are better addressed using data analysis techniques. Here, we make use of the heliocentric range and range-rate of the known Kuiper belt objects and their uncertainties to identify structures in orbital parameter space beyond the Kuiper Cliff. The distribution in heliocentric range there closely resembles that of the outer main asteroid belt with a gap at ∼70 au that may signal the existence of a dynamical analogue of the Jupiter family comets. Outliers in the distribution of mutual nodal distances suggest that a massive perturber is present beyond the heliopause.
A Proofreading Mutation with an Allosteric Effect Allows a Cluster of SARS-CoV-2 Viruses to Rapidly Evolve
Authors: Mack Andrew H , Menzies Georgina , Southgate Alex , Jones D Dafydd , Connor Thomas R 
Published: September 2023

Abstract
The RNA-dependent RNA polymerase of the severe acute respiratory syndrome coronavirus 2 virus is error prone, with errors being corrected by the exonuclease (NSP14) proofreading mechanism. However, the mutagenesis and subsequent evolutionary trajectory of the virus is mediated by the delicate interplay of replicase fidelity and environmental pressures. Here, we have shown that a single, distal mutation (F60S) in NSP14 can have a profound impact upon proofreading with an increased accumulation of mutations and elevated evolutionary rate being observed. Understanding the implications of these changes is crucial, as these underlying mutational processes may have important implications for understanding the population-wide evolution of the virus. This study underscores the urgent need for continued research into the replicative mechanisms of this virus to combat its continued impact on global health, through the re-emergence of immuno-evasive variants.
Detecting Episodic Evolution through Bayesian Inference of Molecular Clock Models
Authors: Tay John H , Baele Guy , Duchene Sebastian 
Published: September 2023

Abstract
Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modeled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However, formal model testing has the advantage of accommodating a wide range molecular clock models. We also assessed the ability of an automated approach, known as the random local clock, where branches under episodic evolution may be detected without their a priori definition. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find “very strong” evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.
Inflammation alters iron distribution in bone and spleen in mice
Authors: Chang JuOae , Debreli Coskun Melis , Kim Jonghan 
Published: September 2023

Abstract
Anemia of inflammation (or inflammation-associated anemia) decreases the quality of life in billions of patients suffering from various inflammatory diseases, such as infection, autoimmune diseases, and cancer, associated with a prolonged state of immune activation. While proper utilization of iron, a nutrient metal essential for erythropoiesis, is important for the prevention of anemia, the alteration of body iron homeostasis upon inflammation, which can contribute to the development of anemia, is not completely understood. Thus, we sought to examine temporal and spatial changes in the distribution of iron and iron-associated molecules during inflammation in mice. To induce inflammation, C57BL/6J mice were injected with turpentine oil weekly for 3 weeks, which resulted in anemia, decreased protein expression of ferroportin, a cellular iron exporter, in the spleen, duodenum, and liver, and increased iron stores in the duodenum and spleen. Tracer kinetic studies after oral administration of 59Fe revealed that more iron was found in the spleen and less in the femur bone in turpentine oil-injected mice compared to the saline-injected mice, indicating tissue-specific abnormalities in iron distribution during inflammation. However, there was no difference in the utilization of iron for red blood cell production after turpentine oil injection; instead, serum hemopexin level and lactate dehydrogenase activity were increased, suggesting increased red blood cell destruction upon inflammation. Our findings provide an improved understanding of temporal and spatial changes in the distribution and utilization of iron during inflammation.
Evolution of Cd2+ and Cu+ binding inHelix pomatiametallothioneins
Authors: Valsecchi Renato , Baumann Christian , Lila Ardit , Zerbe Oliver 
Published: September 2023

AbstractMetallothioneins (MTs) are small proteins present in all kingdoms of life. Their high cysteine content enables them to bind metal ions, such as Zn2+, Cd2+, and Cu+, providing means for detoxification and metal homeostasis. Three MT isoforms with distinct metal binding preferences are present in the Roman Snail Helix pomatia. Here, we use nuclear magnetic resonance (NMR) to follow the evolution of Cd2+ and Cu+ binding from the reconstructed ancestral Stylommatophora MT to the three H. pomatia MT (HpMT) isoforms. Information obtained from [15N,1H]-HSQC spectra and T2 relaxation times are combined to describe the conformational stability of the MT-metal complexes. A well-behaved MT-metal complex adopts a unique structure and does not undergo additional conformational exchange. The ancestor to all three HpMTs forms conformationally stable Cd2+ complexes and closely resembles the Cd2+-specific HpCdMT isoform, suggesting a role in Cd2+ detoxification for the ancestral protein. All Cu+-MT complexes, including the Cu+-specific HpCuMT isoform, undergo a considerable amount of conformational exchange. The unspecific HpCd/CuMT and the Cu+-specific HpCuMT isoforms form Cu+ complexes with comparable characteristics. It is possible to follow how Cd2+ and Cu+ binding changed throughout evolution. Interestingly, Cu+ binding improved independently in the lineages leading to the unspecific and the Cu+-specific HpMT isoforms. C-terminal domains are generally less capable of coordinating the non-cognate metal ion than N-terminal domains, indicating a higher level of specialization of the C-domain. Our findings provide new insights into snail MT evolution, helping to understand the interplay between biological function and structural features toward a comprehensive understanding of metal preference.
Optimizing preclinical pediatric low-grade glioma models for meaningful clinical translation
Authors: Milde Till , Fangusaro Jason , Fisher Michael J , Hawkins Cynthia , Rodriguez Fausto J , Tabori Uri , Witt Olaf , Zhu Yuan , Gutmann David H 
Published: September 2023

Abstract
Pediatric low-grade gliomas (pLGGs) are the most common brain tumor in young children. While they are typically associated with good overall survival, children with these central nervous system tumors often experience chronic tumor- and therapy-related morbidities. Moreover, individuals with unresectable tumors frequently have multiple recurrences and persistent neurological symptoms. Deep molecular analyses of pLGGs reveal that they are caused by genetic alterations that converge on a single mitogenic pathway (MEK/ERK), but their growth is heavily influenced by nonneoplastic cells (neurons, T cells, microglia) in their local microenvironment. The interplay between neoplastic cell MEK/ERK pathway activation and stromal cell support necessitates the use of predictive preclinical models to identify the most promising drug candidates for clinical evaluation. As part of a series of white papers focused on pLGGs, we discuss the current status of preclinical pLGG modeling, with the goal of improving clinical translation for children with these common brain tumors.
Taxane-Based Chemotherapy Is Effective in Metastatic Appendiceal Adenocarcinoma
Authors: Dansby Julia , More Aditya , Zeineddine Mohammad , Yousef Abdelrahman , Bent Alisha , Dayyani Farshid , Wolff Robert , Overman Michael , Shen John Paul 
Published: September 2023

Abstract
Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study to assess efficacy. In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months. Of 10 evaluable patients, we observed 3 responses, 4 patients with stable disease, and 3 with progression (30% response rate, 70% disease control rate). The results of this study showing activity of taxane-based chemotherapy in appendiceal adenocarcinoma support further clinical investigation of taxane therapy in this orphan disease.
Informality, Consumption Taxes, and Redistribution
Authors: Bachas Pierre , Gadenne Lucie , Jensen Anders 
Published: September 2023

Abstract
Can taxes on consumption redistribute in developing countries? Contrary to consensus, we show that taxing consumption is progressive once we account for informal consumption. Using household expenditure surveys in 32 countries, we proxy for informal consumption using the type of store where purchases occur. We establish that the budget share spent in informal stores steeply declines with income, so that richer households pay a substantially larger share of their income in taxes. Our findings imply that the widespread policy of exempting food from taxation is hard to justify on equity grounds in low-income countries.
A Global, Regional, and National Burden and Quality of Care Index for Schizophrenia: Global Burden of Disease Systematic Analysis 1990–2019
Authors: Same Kaveh , Shobeiri Parnian , Rashidi Mohammad-Mahdi , Ghasemi Erfan , Saeedi Moghaddam Sahar , Mohammadi Esmaeil , Masinaei Masoud , Salehi Niloufar , Mohammadi Fateh Sahar , Farzad Maroufi Seyed , Abdolhamidi Elham , Moghimi Mana , Abbasi-Kangevari Zeinab , Rezaei Negar , Larijani Bagher 
Published: September 2023

Abstract

Background and Hypothesis
Schizophrenia is a mental disorder usually presented in adulthood that affects roughly 0.3 percent of the population. The disease contributes to more than 13 million years lived with disability the global burden of disease. The current study aimed to provide new insights into the quality of care in Schizophrenia via the implementation of the newly introduced quality of care index (QCI) into the existing data.

Study Design
The data from the global burden of disease database was used for schizophrenia. Two secondary indices were calculated from the available indices and used in a principal component analysis to develop a proxy of QCI for each country. The QCI was then compared between different sociodemographic index (SDI) and ages. To assess the disparity in QCI between the sexes, the gender disparity ratio (GDR) was also calculated and analyzed in different ages and SDIs.

Study Results
The global QCI proxy score has improved between 1990 and 2019 by roughly 13.5%. Concerning the gender disparity, along with a rise in overall GDR the number of countries having a GDR score of around one has decreased which indicates an increase in gender disparity regarding quality of care of schizophrenia. Bhutan and Singapore had 2 of the highest QCIs in 2019 while also showing GDR scores close to one.

Conclusions
While the overall conditions in the quality of care have improved, significant disparities and differences still exist between different countries, genders, and ages in the quality of care regarding schizophrenia.