bluuebunny/crossref_metadata_2025_split huggingface dataset:
GBA1 as a risk gene for osteoporosis in the specific populations and its role in the development of Gaucher disease
Authors: Wang Chung-Hsing , Huang Yu‐Nan , Liao Wen-Ling , Hsieh Ai-Ru , Lin Wei-De , Liu Kai-Wen , Lu Wen-Li , Huang Chieh‐Chen , Chien Yin-Hsiu , Lee Ni-Chung , Su Pen-Hua , Tsai Fuu-Jen 
Published: April 2024

AbstractBackgroundOsteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations.MethodsWe selected 8115 patients with osteoporosis (T-score ≤ − 2.5) and 55,942 healthy individuals (T-score > − 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient’s cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period.ResultsThe GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density.ConclusionsElevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis.
Social support and medication adherence among adult myasthenia gravis patients in China: the mediating role of mental health and self-efficacy
Authors: Yu Jiazhou , Xie Luyao , Chen Shanquan , Fang Zhilan , Zhu Liling , Zhang Huanyu , Xu Richard H. , Yang Huan , Dong Dong 
Published: April 2024

Abstract
Background
Myasthenia gravis (MG), a rare chronic neuromuscular disorder, is characterized by progressive physical decline and requires long-term pharmacological treatment. Due to the decline of physical and social abilities, MG patients are in great need of social support, including tangible and emotional support. This study aims to examine the association between social support and medication adherence and the possible mediating effects of mental health and self-efficacy among MG patients.

Methods
A cross-sectional analysis of a nationwide MG registry was conducted on 865 patients under oral medication treatment in China between June and July 2022. Validated scales were used to measure the respondent’s mental distress (Four-item Patient Health Questionnaire), social support (Modified Medical Outcomes Study Social Support Scale), self-efficacy for medication use (Self-efficacy for Appropriate Medication Use Scale), and medication adherence (Morisky Medication Adherence Scale, MMAS).

Results
The association between social support and medication adherence and possible mediating effects of mental distress and self-efficacy were tested by structural equation model, with significant demographic and disease-related factors adjusted. The respondents showed a very low level of medication adherence (71.2% poor adherence; 1.4% high adherence; mean MMAS = 4.65). The level of social support was positively associated with medication adherence, and such association was fully mediated by two indirect pathways: through self-efficacy (β = 0.07, proportion mediated = 63.8%); and through mental distress and then self-efficacy (β = 0.01, proportion mediated = 6.7%).

Conclusion
Provision of social support and interventions on mental health with emphasis on improving self-efficacy for medication use may effectively improve medication adherence among MG patients.
Enhanced therapeutic potential of antibody fragment via IEDDA-mediated site-specific albumin conjugation
Authors: Go Eun Byeol , Lee Jae Hun , Cho Jeong Haeng , Kwon Na Hyun , Choi Jong-il , Kwon Inchan 
Published: April 2024

Abstract
Background
The use of single-chain variable fragments (scFvs) for treating human diseases, such as cancer and immune system disorders, has attracted significant attention. However, a critical drawback of scFv is its extremely short serum half-life, which limits its therapeutic potential. Thus, there is a critical need to prolong the serum half-life of the scFv for clinical applications. One promising serum half-life extender for therapeutic proteins is human serum albumin (HSA), which is the most abundant protein in human serum, known to have an exceptionally long serum half-life. However, conjugating a macromolecular half-life extender to a small protein, such as scFv, often results in a significant loss of its critical properties.

Results
In this study, we conjugated the HSA to a permissive site of scFv to improve pharmacokinetic profiles. To ensure minimal damage to the antigen-binding capacity of scFv upon HSA conjugation, we employed a site-specific conjugation approach using a heterobifunctional crosslinker that facilitates thiol-maleimide reaction and inverse electron-demand Diels-Alder reaction (IEDDA). As a model protein, we selected 4D5scFv, derived from trastuzumab, a therapeutic antibody used in human epithermal growth factor 2 (HER2)-positive breast cancer treatment. We introduced a phenylalanine analog containing a very reactive tetrazine group (frTet) at conjugation site candidates predicted by computational methods. Using the linker TCO-PEG4-MAL, a single HSA molecule was site-specifically conjugated to the 4D5scFv (4D5scFv-HSA). The 4D5scFv-HSA conjugate exhibited HER2 binding affinity comparable to that of unmodified 4D5scFv. Furthermore, in pharmacokinetic profile in mice, the serum half-life of 4D5scFv-HSA was approximately 12 h, which is 85 times longer than that of 4D5scFv.

Conclusions
The antigen binding results and pharmacokinetic profile of 4D5scFv-HSA demonstrate that the site-specifically albumin-conjugated scFv retained its binding affinity with a prolonged serum half-life. In conclusion, we developed an effective strategy to prepare site-specifically albumin-conjugated 4D5scFv, which can have versatile clinical applications with improved efficacy.
A vocal cord palsy caused by the uterine cancer metastatic tumor in the mediastinum revealed in a patient with a thyroid lesion: a case report and review of the literature
Authors: Hryshchyshyn Andrii , Bahrii Andrii , Bazyshen Andrii , Bohush Hryhorii 
Published: April 2024

Abstract
Background
The main cause of vocal cord palsy (VCP) is idiopathic impairment of the recurrent laryngeal nerve (RLN). However, solid tumors along the pathway of the RLN can also impact the nerve’s function. We presented a patient with a thyroid lesion and VCP due to a bulky metastatic mass (uterine cancer) on the aortic arch field in the mediastinum. The report aims to show the significance of comorbid tumors in thyroid pathology and the importance of additional diagnostic methods in avoiding unnecessary surgeries. A patient’s lifetime and the outcome of the disease were also presented.

Case presentation
A 58-year-old Ukrainian woman with a hoarse voice, intermittent dry cough, and weakness was presented to an endocrine surgeon. Thyroid pathology included signs of hypothyroidism treated with Thyroxine 112.5 µg and a nodule in the left lobe. The lesion is located on the posterior aspect of the lobe, which could probably be a cause of RLN involvement. Fine needle aspiration biopsy (FNAB) was performed twice with Bethesda category 2 result. Fibrolaryngoscopy (FLS) revealed the median position of the left vocal cord. Idiopathic, laryngeal, and thyroid causes of the VCP were excluded. Additionally, the patient displayed her anamnesis of the endometrial clear cell carcinoma following hysterectomy, external beam radiation therapy, and chemotherapy. The mediastinal metastasis was revealed sixteen years later. A chest computed tomography (CT) with intravenous contrast was done. A bulky tumor was found right under the aortic arch. Subsequently, the voice complaints reduced significantly after 4 chemotherapy courses. Cancer progression had led to the appearance of lymph node metastases on the supraclavicular region. Following six months the 60-year-old patient had passed away.

Conclusion
A history of the disease should always be kept in mind when assessing a patient’s complaints. VCP in case of thyroid pathology and previous secondary malignancy may be caused by metastatic tumor anywhere along the RLN pathway. Such a rare case shows the importance of additional methods of examination which may avoid unnecessary thyroid surgeries.
Establishment of stellate ganglion block in mice
Authors: Duan Qirui , Zhou Ying , Zhi Juan , Liu Quanle , Xu Jin , Yang Dong 
Published: April 2024

Abstract
Background
There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice.

Objectives
This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand.

Methods
Fifty BABL/C mice, 8–10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed.

Results
Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708–726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5–491], median [IQR], bpm) (P < 0.05). While the heart rate was slowed down after performing the left SGB, the difference was not statistically significant (P > 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found.

Conclusions
This method allows for the successful implementation of SGB in a mouse model.
Models and tools for the digital organisation of knowledge: accessible and adaptive narratives for cultural heritage
Authors: Nappi Maria Laura , Buono Mario , Chivăran Camelia , Giusto Rosa Maria 
Published: April 2024

Abstract
The cultural heritage sector includes a significant variety and complexity of data and information. Making this accessible today represents one of the main aims of cultural institutes. The connections between digital archives and knowledge enable the extension of this wealth of information beyond the physical existence of cultural assets by fostering the creation of digital libraries based on the comparison and interaction of data and on sharing the most up-to-date scientific literature. To this purpose, the results of the analysis on the Italian system of cataloguing and dissemination of knowledge related to cultural heritage are first illustrated. These are indispensable for enhancing the experience of cultural heritage, starting from guidebooks and travel literature, which represent the first codified forms of description of cultural heritage addressed to an audience of visitors/users, and ending with the most recent ways of sharing knowledge related to cultural heritage. Among these, digital platforms for participatory storytelling and the drafting of innovative texts and narratives stand out. Particular attention is paid to the innovative models for the use and enjoyment of cultural heritage employed in some of the main institutes and museums, where examples are analysed to effectively illustrate the emergence of new forms and modes of knowledge and narrative of cultural heritage, between big data and digital devices. Through these analyses, this article provides an overall picture of the current models and methods for the digital organisation of cultural heritage knowledge in order to raise awareness of the main critical issues encountered and to activate targeted planning and design processes capable of responding adequately to the needs of an increasingly active and participative user base in the processes of learning and enjoyment of cultural heritage. The interactions between scientific and technological research characterise the field of cultural heritage knowledge and are both instrumental in facilitating established approaches and contribute to changing the very parameters of research by posing new epistemological questions.
Unveiling the mechanism of diachronic changes and regional characteristics differences in the built environment of traditional villages from the perspective of color data: evidence from Macheng City, China
Authors: Tan Gangyi , Chen Zhanxiang , Xue Miao , Jia Yanfei 
Published: April 2024

Abstract
Traditional villages hold a vital place in Chinese vernacular built heritage continuation with their colors being a significant constituent of the built environment. While digital technology has advanced our understanding of built environment, current research pays little attention on how color influences the environment, often overlooking temporal changes and regional differences, especially neglects color protection measures. This study establishes an diachronic image dataset using national traditional villages in Macheng City, Hubei Province. By using of K-Means and CIEDE2000 algorithms, we analyze color characteristics differences among 4 regions in Macheng City in 2022. And, we select five year’ s diachronic image data of Dongyuan Village (2017–2022) to elucidate the color changes mechanisms. The results show that: (1) Elements influenced by the government, construction techniques dissemination, and environmental factors exhibit regional similarity, while the color of wall differs significantly. Specifically, K-Means values for northern and eastern wall elements indicate light brown tones [RGB: (159, 151, 136), (163, 159, 147)], whereas southwestern and central wall elements exhibit distinct colors, including grayish brown [RGB: (132, 127, 119)] and light yellow [RGB: (190, 182, 161)], respectively. (2) Dongyuan Village underwent color corrections in accordance with government policies, resulting in a shift from blue [RGB: (138, 154, 213)] to yellow [RGB: (223, 206, 196)] for the walls and a gradual unification of road colors into light gray [RGB: (239, 238, 243)]. This initiative led to increased consistency with government guidelines, and the color data stabilized with minimal changes in the surrounding environment. This study enhances our comprehension of traditional village color and regional characteristics changes, contributing to effective measures for the preservation of these culturally significant built heritage.
Susceptibility of immature Telenomus remus, an egg parasitoid of Spodoptera frugiperda (J.E. Smith), to entomopathogenic fungi from South Sumatra, Indonesia
Authors: Putri Qarina Shafira , Oktapiani Wenti , Herlinda Siti , Suwandi Suwandi 
Published: April 2024

Abstract
Background
The fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is a newly introduced pest that damages maize production in Indonesia. To control this pest in maize fields, better solution is to use the egg parasitoid, such as Telenomus remus Nixon (Hymenoptera: Scelionidae), as another better option to apply topically entomopathogenic fungi (EPF). Therefore, it is necessary to study the effect of the EPF on the egg parasitoid of T. remus. The objective of this research was to evaluate susceptibility of immature T. remus to the EPFs, Beauveria bassiana, Chaetomium sp., Curvularia lunata, Penicillium citrinum, and Metarhizium anisopliae. The EPFs (1 × 106 conidia mL−1) were sprayed topically on one-day-old mummies (immature T. remus) in post-parasitism periods.

Results
The results showed that the cumulative percentage of T. remus adult emergence from the mummies treated with EPF on 11 days after treatment ranged 54–100% and was non-significantly different than those of control (untreated with EPF) (90.48%). Therefore, the immature stage of T. remus was not susceptible to the EPF topical application. The EPFs were harmless to the immature stage of T. remus. Percentage of aborted mummies (embryonic death) of T. remus after treated with the EPF was also non-significantly different than those of control. However, the EPFs could significantly affect developmental times of immatures stages of T. remus. The EPF also could shorten the adult longevity of the egg parasitoid.

Conclusions
The immature T. remus is less sensitive to the EPFs; B. bassiana, Chaetomium sp., C. lunata, P. citrinum, and M. anisopliae. It can be considered integrating the EPF with T. remus inundation in maize field. However, it is necessary to limit the topical application of the EPF to avoid negative effects on the adult longevity of the egg parasitoid. Thus, it needed to be further investigated that the application of the endophytic EPFs by inoculating the fungi within the plant tissue could be harmless to the egg parasitoids.
Impact of change in coronal plane alignment of knee (CPAK) classification on outcomes of robotic-assisted TKA
Authors: Agarwal Sarang , Ayeni Femi E. , Sorial Rami 
Published: April 2024

Abstract
Background
Mechanical alignment with total knee arthroplasty (TKA) has been widely used since the implantation of the first prosthetic knee. Multiple studies have reported 80% patient satisfaction with TKA. However, the reported patients’ dissatisfaction is believed to be caused by having to convert different knee alignments to neutral alignments. It is postulated that a change in the CPAK classification of knees leads to patient dissatisfaction.
Thus, we hypothesized that a change in CPAK classification with robot-assisted TKA with mechanical alignment does not significantly lead to patient dissatisfaction.

Methods
We retrospectively analyzed 134 patients who underwent robot-assisted mechanical alignment total knee arthroplasty (MA-TKA) using cementless implants and classified them into CPAK system pre- and post-operatively. One year after TKA surgery, we recorded binary responses to patients’ satisfaction with the outcome of surgery and analyzed if a change in CPAK classification is associated with the outcome of surgery.

Results
We found that 125 out of 134 patients (93.28%) were happy with the outcome of surgery. CPAK classification was changed in 116 patients (86.57%) and maintained in 18 patients (13.43%). Our results also showed that 111 (95.7%) out of 116 patients who had a change in CPAK and 14 (77.8%) out of 18 patients who maintained their CPAK post-surgery were happy with the outcome of surgery (OR = 6.3, CI 1.741–25.17, P value = 0.019).

Conclusion
We concluded that changing the patient’s native joint line and CPAK classification does not significantly change the outcome of surgery in terms of satisfaction. The dissatisfaction rate of 20% as published by previous researchers may be confounded by other reasons and not just due to changes in alignment and joint line.
Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes
Authors: Wen He , Niu Xiaona , Yu Rui , Zhao Ran , Wang Qiuhe , Sun Nan , Ma Le , Li Yan 
Published: April 2024

Abstract

Context
There are insufficient data to support a link between serum albumin-to-globulin ratio (AGR) and mortality in individuals with diabetes.

Objective
This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics.

Methods
This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Hazard ratios (HR) and 95% CIs for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional-hazards models.

Results
A total of 2415 all-cause deaths, including 688 CV deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend &lt; .0001), cardiovascular mortality (Ptrend &lt; .001), and cancer mortality (Ptrend &lt; .01) were 0.51 (0.42-0.60), 0.62 (0.46-0.83), and 0.57 (0.39-0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per 1-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P &lt; .001). Both the stratified analysis and the sensitivity analyses revealed the same relationships.

Conclusion
AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those younger than 60 years and heavy drinkers.
“They Can Never Take it Away from You”
Authors: Hopkins Britain 
Published: April 2024

Abstract
This article uses the contradictions and complicity of conclusions to think through the United States’ collective student loan burden while grounding this burden at its historical roots in the mid-twentieth century. In particular, it is concerned with the impasse surrounding the Biden administration's conclusion of the federal student loan payment pause and demands for full student loan debt cancellation. Reading with Lauren Berlant's Cruel Optimism, it suggests that this impasse entails a relation of optimistic cruelty: the active infliction of the affective and material conditions of capital as a means of leverage over oneself and others to maintain a status quo. Attendantly, this article draws attention to the centrality of liquidity/discipline to the conditions of indebtedness within financial capital, highlighting three foundational developments in the emergence of student loan debt: the creation of the Guaranteed Student Loan Program as the country's first universal program of student loans in 1965; the establishment of the Student Loan Marketing Association as a government-sponsored enterprise to provide private liquidity for the federal program in 1972; and the successful push to enact bankruptcy reforms to protect the viability of Sallie Mae from the early 1970s on. The establishment of liquidity/discipline at the industry's inception has allowed student loan indebtedness to flourish into the present and highlights the optimistic cruelty of concluding the federal payment pause to enforce a wholly insufficient status quo.