bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts
Authors: Atanasova Diana , Mirgorodskaya Ekaterina , Moparthi Lavanya , Koch Stefan , Haarhaus Mathias , Narisawa Sonoko , Millán José Luis , Landberg Eva , Magnusson Per 
Published: January 2024

Abstract
Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.
Flipping the paradigm of weak patent rights: from theories to evidence
Authors: Maronero Cecilia , Bichlmayr Annika 
Published: January 2024

Abstract
In recent years, we have been confronted with complex challenges requiring coordinated global responses, such as the Covid-19 pandemic and climate change. At the same time, a negative sentiment towards IP rights (IPRs)—and patents in particular—has gained momentum. Sceptics claim that patents hinder the technology adoption needed to tackle these global crises, and proposals to weaken patent rights have intensified. A closer examination of these efforts reveals that they are generally expressed in two ways: on one side, anti-patent advocacy is backed up by popular, although empirically shaky, theories aimed at questioning patents’ effectiveness; on the other, the paradigm of weak patents is put forward through more incremental and—only at first glance—subtle policy changes that can potentially undermine the foundations of a balanced patent system. We address and review both efforts. Firstly, we examine the ‘first-mover advantage’ theory and we find it inadequate as a substitute for patent protection. Secondly, we focus on the cellular connectivity sector where efforts to weaken the patent system are intense. We discuss three common policy proposals: (i) royalty-free licensing for standard essential patents (SEPs), (ii) limiting injunctive relief under the proportionality principle and (iii) narrowing patent transfers and technology markets. We demonstrate that these seemingly minor changes can destabilize the patent system, and we explore the importance of a balanced licensing framework for the emergent Internet of Things (IoT). Ultimately, we highlight how a strong, efficient and balanced patent system remains crucial for fostering research and development (R&D), incentivizing innovators and effectively addressing the global challenges of our current times.
Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy
Authors: Yoshida Takahiro , Kawai Taketo , Hagiwara Kanade , Yanagida Kazuki , Noda Michio , Tokura Yuumi , Yoshimura Itsuki , Kaneko Tomoyuki , Nakagawa Tohru 
Published: January 2024

Abstract

Objective
This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy.

Methods
A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals.

Results
During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P &lt; 0.001, respectively). Multivariate analysis identified testosterone level of &lt;450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9–10. Similarly, testosterone level of &lt;450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level.

Conclusions
Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.
Transient receptor potential cation channel subfamily V member 1 (TRPV1) targeted PET imaging
Authors: Tateishi Ukihide , Doi Hisashi 
Published: January 2024

Abstract
Transient receptor potential cation channel subfamily V member 1 (TRPV1) was identified using capsaicin, a pungent compound that is present in red pepper. The activation of TRPV1 induces an influx of calcium ions into cells and causes excitation of sensory neurons, associating with thermal sensing, sweating and pain. TRPV1 is also identified in various types of cancer cells. The expression of TRPV1 in cancer cells depends on the type of cancer and the stage of the disease. Therefore, TRPV1 has been considered a potential target of medicinal chemistry for drug development, and blocking its activation may lead to cancer therapy and pain relief. However, the details of the pathophysiological function of TRPV1 in vivo are still unclear. To explore practical use of TRPV1, we focused on positron emission tomography imaging and developed a 11C-radiolabeled tracer to visualize TRPV1.
Efficacy of radiation therapy in Japanese patients with positive margins after breast-conserving surgery
Authors: Uomori Toshitaka , Horimoto Yoshiya , Ueki Yuko , Ishizuka Yumiko , Onagi Hiroko , Hayashi Takuo , Watanabe Junichiro , Shikama Naoto 
Published: January 2024

Abstract

Background
Additional surgical resection is recommended after breast-conserving surgery if the surgical margin is pathologically positive. However, in clinical practice, radiation therapy is sometimes used instead for several reasons. Irradiation may be appropriate for some patients, but real-world data is still insufficient to establish it as standard treatment. We retrospectively investigated the status of local control in patients who received irradiation for positive margins.

Methods
We investigated 85 patients with positive margins after curative partial mastectomy who were treated with irradiation instead of additional excision during the period 2006–2013. The patients received whole-breast irradiation (43.2–50 Gy) using photon beams and additional tumour-bed boost (8.1–16 Gy) using electron beams. Intrabreast tumour recurrence was defined as secondary cancer within the ipsilateral conserved breast. Surgical margin was defined as positive if tumour cell exposure was pathologically confirmed on the margin.

Results
Seven patients (8.2%) developed intrabreast tumour recurrence during a mean observation period of 119 months. As to components of positive margin, 76 cases were positive for an intraductal component, of which seven (9.2%) developed intrabreast tumour recurrence. Meanwhile, all nine cases positive for an invasive component were free from intrabreast tumour recurrence. Two of the intrabreast tumour recurrence cases seemed to develop new lesions rather than recurrence, considering tumour location. The cumulative incidence of intrabreast tumour recurrence over 10 years was 6.1%. Limited to true recurrence, intrabreast tumour recurrence incidence was 4.9%.

Conclusion
Our real-world data supports irradiation as an alternative to additional surgical intervention for positive margins after breast-conserving surgery and offers a basis for further research.
Viral presence and immunopathology in a kidney transplant recipient with fatal COVID-19: a clinical autopsy report
Authors: van Eijk Larissa E , Bourgonje Arno R , Mastik Mirjam F , Snippe Dirk , Bulthuis Marian L C , Vos Wim , Bugiani Marianna , Smit Jolanda M , Berger Stefan P , van der Voort Peter H J , van Goor Harry , den Dunnen Wilfred F A , Hillebrands Jan-Luuk 
Published: January 2024

Abstract
COVID-19 is of special concern to immunocompromised individuals, including organ transplant recipients. However, the exact implications of COVID-19 for the immunocompromised host remain unclear. Existing theories regarding this matter are controversial and mainly based on clinical observations. Here, the postmortem histopathology, immunopathology, and viral presence in various tissues of a kidney transplant recipient with COVID-19 were compared to those of 2 nontransplanted patients with COVID-19 matched for age, sex, length of intensive care unit stay, and admission period in the pandemic. None of the tissues of the kidney transplant recipient demonstrated the presence of SARS-CoV-2. In lung tissues of both controls, some samples showed viral positivity with high Ct values with quantitative reverse transcription polymerase chain reaction. The lungs of the kidney transplant recipient and controls demonstrated similar pathology, consisting of acute fibrinous and organizing pneumonia with thrombosis and an inflammatory response with T cells, B cells, and macrophages. The kidney allograft and control kidneys showed a similar pattern of interstitial lymphoplasmacytic infiltration. No myocarditis could be observed in the hearts of the kidney transplant recipient and controls, although all cases contained scattered lymphoplasmacytic infiltrates in the myocardium, pericardium, and atria. The brainstems of the kidney transplant recipient and controls showed a similar pattern of lymphocytic inflammation with microgliosis. This research report highlights the possibility that, based on the results obtained from this single case, at time of death, the immune response in kidney transplant recipients with long-term antirejection immunosuppression use prior to severe illness is similar to nontransplanted deceased COVID-19 patients.
Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study)
Authors: Schüz Joachim , Kovalevskiy Evgeny , Olsson Ann , Moissonnier Monika , Ostroumova Evgenia , Ferro Gilles , Feletto Eleonora , Schonfeld Sara J , Byrnes Graham , Tskhomariia Iraklii , Straif Kurt , Morozova Tatiana , Kromhout Hans , Bukhtiyarov Igor 
Published: January 2024

Abstract

Background
We investigated mortality in workers of the world’s largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.

Methods
This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers’ complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.

Results
A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.

Conclusion
In this large-scale epidemiological study in the world’s largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.
Critical mass condition of majority bureaucratic behavioral change in representative bureaucracy: a theoretical clarification and a nonparametric exploration
Authors: Li Danyao 
Published: January 2024

Abstract
Representative bureaucracy theory examines how bureaucrats’ demographics impact outcomes for clients with shared identities, with “critical mass” posited as an enabling condition. Yet empirical evidence is mixed regarding where this threshold stands. To reconcile these inconsistencies, this study emphasizes the need to first clarify the mechanisms that underpin critical mass requirements. Specifically, I attend to how majority behavior changes due to enhanced representation and evaluate corresponding critical mass condition. Nonparametric analyses of traffic stop data in two states find that, in Washington, the critical mass where White officers show reduced bias towards Black drivers occurs when Black officers constitute 6–9 percent of the force. In South Carolina, similar shifts occur at 9–11 and 19–23 percent Black representation. While findings indicate improved policing towards Black drivers, increased representation still falls short of achieving full parity between Black and White drivers. No significant critical mass is observed for Hispanic representation in either state.
Religious influence and its protection
Authors: Lewin David 
Published: January 2024

Abstract
John Tillson’s book Children, Religion and the Ethics of Influence addresses several themes: the ground and nature of ethical responsibility; the means and goals of ethical formative influence; the nature and ground of religious belief. In this article, I focus on the issue of justification for educational influence in general. Attention to this issue could avoid some intractable problems of specifically religious influence, most particularly the challenge of providing satisfactory criteria for what belongs to the category of religion. Whilst there may be important reasons for examining specifically religious influence, I argue that religious influence is not fundamentally different from other forms of influence, and that the logic of the ethics of influence in general would encompass the logic of religious influence. If the educator is to justify certain forms of influence, then they should employ a kind of restraint: the educator should influence whilst simultaneously protect the influencee from that very influence.
Gradient synchronization for multivariate functional data, with application to brain connectivity
Authors: Chen Yaqing , Lin Shu-Chin , Zhou Yang , Carmichael Owen , Müller Hans-Georg , Wang Jane-Ling 
Published: January 2024

Abstract
Quantifying the association between components of multivariate random curves is of general interest and is a ubiquitous and basic problem that can be addressed with functional data analysis. An important application is the problem of assessing functional connectivity based on functional magnetic resonance imaging (fMRI), where one aims to determine the similarity of fMRI time courses that are recorded on anatomically separated brain regions. In the functional brain connectivity literature, the static temporal Pearson correlation has been the prevailing measure for functional connectivity. However, recent research has revealed temporally changing patterns of functional connectivity, leading to the study of dynamic functional connectivity. This motivates new similarity measures for pairs of random curves that reflect the dynamic features of functional similarity. Specifically, we introduce gradient synchronization measures in a general setting. These similarity measures are based on the concordance and discordance of the gradients between paired smooth random functions. Asymptotic normality of the proposed estimates is obtained under regularity conditions. We illustrate the proposed synchronization measures via simulations and an application to resting-state fMRI signals from the Alzheimer’s Disease Neuroimaging Initiative and they are found to improve discrimination between subjects with different disease status.
What We Know About Homeless Veterans With Other-than-honorable and Punitive Discharges: Data From the Grant and Per Diem (GPD) Program
Authors: Jutkowitz Eric , McCreedy Ellen , Halladay Christopher , Tsai Jack 
Published: January 2024

ABSTRACT

Introduction
The U.S. DVA Grant and Per Diem (GPD) program funds community agencies to provide housing and case management services to Veterans experiencing homelessness. GPD is one of the few VA programs that can enroll Veterans with Other-than-Honorable (OTH) military discharges. The characteristics of OTH Veterans and their outcomes in GPD are unknown.

Materials and Methods
We linked the Homeless Operations and Management Evaluation System database and VA Corporate Data Warehouse to identify Veterans with complete GPD enrollment and discharge data between 2018 and 2020. We categorized Veterans into three military discharge groups: Honorable, OTH, or Punitive. We evaluated key GPD process and outcomes measures: days enrolled in GPD, use of VA-funded emergency department care while in GPD, and whether a Veteran was successfully discharged from GPD, their housing status at program exit, employment status at program exit, and connection to mental health and substance abuse treatment at discharge. We conducted multivariable regressions to determine the adjusted association (controlling for demographics and comorbidities) between military discharge status and process and outcome measures.

Results
Among 21,646 Veterans in the GPD program, 20,517 (95%) were honorably discharged; 811 (4%) had an OTH discharge; and 318 (1%) had a Punitive discharge. There was no difference in GPD length of enrollment by discharge status. Compared to honorably discharged veterans, OTH and Punitive discharged Veterans were less likely to successfully exit GPD, more likely to be homeless and employed at program exit, and were less likely to have a VA-funded emergency department visit while in GPD and less likely to be connected to mental health care or substance use treatment at program exit.

Conclusions
The GPD program serves hundreds of homeless Veterans with OTH and Punitive discharges every year, but they seem to be at greater risk for negative health and psychosocial outcomes and do not have the same access to VA services as other Veterans. These findings may inform policy considerations about expanding VA care and opportunities for community providers to serve Veterans with OTH and Punitive discharges.
Simultaneous observations of a breakout current sheet and a flare current sheet in a coronal jet event
Authors: Yang Liheng , Yan Xiaoli , Xue Zhike , Xu Zhe , Zhang Qingmin , Hou Yijun , Wang Jincheng , Chen Huadong , Li Qiaoling 
Published: January 2024

ABSTRACT
Previous studies have revealed that solar coronal jets triggered by the eruption of minifilaments (MFs) conform to the famous magnetic-breakout mechanism. In such a scenario, a breakout current sheet (BCS) and a flare current sheet (FCS) should be observed during the jets. With high spatial and temporal resolution data from the SDO, the NVST, the RHESSI, the Wind, and the GOES, we present observational evidence of a BCS and a FCS formation during coronal jets driven by a MF eruption occurring in the active region NOAA 11726 on 2013 April 21. Magnetic field extrapolation shows that the MF was enclosed by a fan-spine magnetic structure. The MF was activated by flux cancellation under it, and then slowly rose. A BCS formed when the magnetic fields wrapping the MF squeezed to antidirectional external open fields. Simultaneously, one thin bright jet and two bidirectional jet-like structures were observed. As the MF erupted as a blowout jet, a FCS was formed when the two distended legs inside the MF field came together. One end of the FCS connected the post-flare loops. The BCS’s peak temperature was calculated to be 2.5 MK. The FCS’s length, width, and peak temperature were calculated to be 4.35–4.93, 1.31–1.45, and 2.5 MK, respectively. The magnetic reconnection rate associated with the FCS was estimated to be from 0.266 to 0.333. This event is also related to a type III radio burst, indicating its influence on interplanetary space. These observations support the scenario of the breakout model as the trigger mechanism of coronal jets, and flux cancellation was the driver of this event.