bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule imaging of Tau reveals how phosphorylation affects its movement and confinement in living cells
Authors: Padmanabhan Pranesh , Kneynsberg Andrew , Cruz Esteban , Briner Adam , Götz Jürgen 
Published: February 2024

AbstractTau is a microtubule-associated protein that is regulated by post-translational modifications. The most studied of these modifications is phosphorylation, which affects Tau’s aggregation and loss- and gain-of-functions, including the interaction with microtubules, in Alzheimer’s disease and primary tauopathies. However, little is known about how Tau’s phosphorylation state affects its dynamics and organisation at the single-molecule level. Here, using quantitative single-molecule localisation microscopy, we examined how mimicking or abrogating phosphorylation at 14 disease-associated serine and threonine residues through mutagenesis influences the behaviour of Tau in live Neuro-2a cells. We observed that both pseudohyperphosphorylated Tau (TauE14) and phosphorylation-deficient Tau (TauA14) exhibit a heterogeneous mobility pattern near the plasma membrane. Notably, we found that the mobility of TauE14 molecules was higher than wild-type Tau molecules, while TauA14 molecules displayed lower mobility. Moreover, TauA14 was organised in a filament-like structure resembling cytoskeletal filaments, within which TauA14 exhibited spatial and kinetic heterogeneity. Our study provides a direct visualisation of how the phosphorylation state of Tau affects its spatial and temporal organisation, presumably reflecting the phosphorylation-dependent changes in the interactions between Tau and its partners. We suggest that alterations in Tau dynamics resulting from aberrant changes in phosphorylation could be a critical step in its pathological dysregulation.
From glioma gloom to immune bloom: unveiling novel immunotherapeutic paradigms-a review
Authors: Regmi Moksada , Wang Yingjie , Liu Weihai , Dai Yuwei , Liu Shikun , Ma Ke , Lin Guozhong , Yang Jun , Liu Hongyi , Wu Jian , Yang Chenlong 
Published: February 2024

AbstractIn tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.
From clinical management to personalized medicine: novel therapeutic approaches for ovarian clear cell cancer
Authors: Liu Zesi , Jing Chunli , Kong Fandou 
Published: February 2024

AbstractOvarian clear-cell cancer is a rare subtype of epithelial ovarian cancer with unique clinical and biological features. Despite optimal cytoreductive surgery and platinum-based chemotherapy being the standard of care, most patients experience drug resistance and a poor prognosis. Therefore, novel therapeutic approaches have been developed, including immune checkpoint blockade, angiogenesis-targeted therapy, ARID1A synthetic lethal interactions, targeting hepatocyte nuclear factor 1β, and ferroptosis. Refining predictive biomarkers can lead to more personalized medicine, identifying patients who would benefit from chemotherapy, targeted therapy, or immunotherapy. Collaboration between academic research groups is crucial for developing prognostic outcomes and conducting clinical trials to advance treatment for ovarian clear-cell cancer. Immediate progress is essential, and research efforts should prioritize the development of more effective therapeutic strategies to benefit all patients.
Discovery of dual kinase inhibitors targeting VEGFR2 and FAK: structure-based pharmacophore modeling, virtual screening, and molecular docking studies
Authors: Fouad Marwa A. , Osman Alaa A. , Abdelhamid Noha M. , Rashad Mai W. , Nabawy Ashrakat Y. , El Kerdawy Ahmed M. 
Published: February 2024

AbstractVEGFR2 and FAK signaling pathways are interconnected and have synergistic effects on tumor angiogenesis, growth, and metastasis. Thus, instead of the conventional targeting of each of these proteins individually with a specific inhibitor, the present work aimed to discover novel dual inhibitors targeting both VEGFR2 and FAK exploiting their association. To this end, receptor-based pharmacophore modeling technique was opted to generate 3D pharmacophore models for VEGFR2 and FAK type II kinase inhibitors. The generated pharmacophore models were validated by assessing their ability to discriminate between active and decoy compounds in a pre-compiled test set of VEGFR2 and FAK active compounds and decoys. ZINCPharmer web tool was then used to screen the ZINC database purchasable subset using the validated pharmacophore models retrieving 42,616 hits for VEGFR2 and 28,475 hits for FAK. Subsequently, they were filtered using various filters leaving 13,023 and 6,832 survived compounds for VEGFR2 and FAK, respectively, with 124 common compounds. Based on molecular docking simulations, thirteen compounds were found to satisfy all necessary interactions with VEGFR2 and FAK kinase domains. Thus, they are predicted to have a possible dual VEGFR2/FAK inhibitory activity. Finally, SwissADME web tool showed that compound ZINC09875266 is not only promising in terms of binding pattern to our target kinases, but also in terms of pharmacokinetic properties.
Mental health problems, sleep quality and overuse injuries in advanced Swedish rock-climbers – the CLIMB study
Authors: Identeg Fredrik , Nigicser Isabel , Edlund Klara , Forsberg Niklas , Sansone Mikael , Tranaeus Ulrika , Hedelin Henrik 
Published: February 2024

Abstract
Objectives
To examine the prevalence of mental health problems (depression, anxiety, and stress), sleep quality, and disability due to overuse injuries in advanced and elite rock-climbers. The rock-climbers were compared to a group of non-climbing controls.

Methods
A self-selected sample of advanced and elite Swedish rock-climbing athletes was recruited through the Swedish Rock-climbing Federation, local rock-climbing gyms and through social media. A control group, matched in size was recruited. Participants in the control group answered an online survey of validated questionnaires, examining symptoms of stress, anxiety, depression, sleep quality. The climbing participants answered the same survey as the non-climbing controls but with additional questions regarding musculoskeletal problems and disabilities related to these. Outcome measures used were the Depression Anxiety Stress Scale, Pittsburgh Sleep Quality Index and The Oslo Sports Trauma Research Center Overuse Injury Questionnaire.

Results
A total of 183 participants were included in the rock-climbing group, and 180 participants in the control group. In the rock-climbing group the mean age (SD) was 28.2 (8.3) years among women and 30.5 (9.6) years in men. The mean BMI of women was 21.2 (2.2) and 22.8 (2.1) in men. A total of 30.6% of the rock-climbing group (26.7% of men, 35.9% of women) reported at least moderate levels of symptoms of depression and 23.1% (17.2% men, 30.8% women) at least moderate levels of symptoms of anxiety. A total of 48.4% of rock-climbers (39.1% men, and 61.6% women) reported at least moderate levels of symptoms of stress. Among the rock-climbers, 45.0% reported having poor sleep quality. There were no statistical significant differences (p = 0.052–0.96) in mental health problems or sleeping problems between the rock-climbers and the controls. Among rock-climbers, reports of one-week prevalence of injury related problems was: Finger and hand (49.5%), Shoulder (35.2%), Knee (29.1%), Lumbar back (26.4%), Arm (25.3%), Thoracic back and neck (17.0%), and Foot and lower leg (12.1%).

Conclusion
The overall results indicate high levels of symptoms of mental health problems and poor sleep quality in both rock-climbers and controls. Although no significant differences between the climbing group and the control group was displayed, symptoms that warrant clinical attention is high. Overuse injuries were commonly reported among the rock-climbers in all examined injury locations. Previous studies reporting mental health problems to be more prevalent among athletes were contradicted in this study. The results display the need for a broader perspective regarding climbers general health and the need to provide structured care and adequate support in order to come to terms with these concerns.
Relationship between shoulder and elbow range of motion and ultrasonographic structural abnormalities in the elbow of Taiwanese high school baseball players
Authors: Lu Yi , Chen Poyu , Chou Wen-Yi , Yang Cheng-Pang , Sheu Huan , Tang Hao-Che , Weng Chun-Jui , Chiu Joe Chih-Hao 
Published: February 2024

Abstract
Background
Ultrasonographic structural abnormalities are regarded as one of the risk factors of elbow injuries. Elbow injuries are commonly associated with decreased shoulder/elbow range of motion (ROM). The purpose of this study is to determine the relationship between shoulder/elbow ROM and elbow ultrasonographic structural abnormalities in Taiwan high school baseball players.

Methods
A total of 533 Taiwan high school baseball players were enrolled. Physical examinations including measurements on shoulder/elbow ROM and elbow sonographic examinations were performed and recorded by professional physicians. The analyses were conducted in three subgroups according to their defensive position because the training programs were different. All players pooled, pitchers-only, and fielders-only, due to several demographic differences among these subgroups. In all the subgroups, univariate analyses were conducted separately for participants with and those without elbow ultrasonographic structural abnormalities, and then multivariate analyses were conducted to identify factors significantly related. The odds ratios (ORs) were used to estimate the risk of elbow ultrasonographic structural abnormalities.

Results
Demographic data showed that pitchers had taller body height (P < 0.001) and greater elbow flexion/extension ROM (P < 0.001). When all players were pooled, significant risk factors included started playing baseball at an younger age (OR = 1.202; 95% CI = 1.064–1.357; P = 0.003), longer experience of official baseball (OR = 1.154; 95% CI = 1.038–1.283; P = 0.008), lower total shoulder rotation angle (OR = 1.007; 95% CI = 1.000–1.014; P = 0.050), and less total elbow arm angle (OR = 1.052; 95% CI = 1.017–1.088; P = 0.003) For pitchers, significant risk factors included longer experience of official baseball (OR = 1.342; 95% CI = 1.098–1.640; P = 0.004), lower total shoulder rotation angle (OR = 1.016; 95% CI = 1.004–1.027; P = 0.006), and lower total elbow arm angle (OR = 1.075; 95% CI = 1.024–1.129; P = 0.004) (Table 5). There were no significant risk factors for elbow structural abnormalities in fielders.

Conclusion
For Taiwan high school pitchers, longer official baseball experience, decreased shoulder total rotational angle, and decreased elbow total flexion/extension angle, were related to ultrasonographic structural abnormalities in elbows.
Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression
Authors: Sagy Naor , Meyrom Noa , Beckerman Pazit , Pleniceanu Oren , Bar Daniel Z. 
Published: February 2024

Abstract
Background
Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood. Kidney fibrosis is the common pathway for chronic kidney disease, which affects 10% of European and US populations.

Results
Here we identify epigenetic clocks and methylation sites that correlate with kidney function. Moreover, we identify methylation sites that have a unique methylation signature in the kidney. Methylation levels in majority of these sites correlate with kidney state and function. When kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Interestingly, while the majority of sites are less methylated in the kidney and become more methylated with loss of function, a fraction of the sites are highly methylated in the kidney and become less methylated when kidney function declines. These methylation sites are enriched for specific transcription-factor binding sites. In a large subset of sites, changes in methylation patterns are accompanied by changes in gene expression in kidneys of chronic kidney disease patients.

Conclusions
These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines. However, this information loss is not random, but guided toward a baseline that is dependent on the genomic loci.

Significance statement
DNA methylation at specific sites accurately reflects chronological and biological age. We identify sites that have a unique methylation pattern in the kidney. Methylation levels in the majority of these sites correlate with kidney state and function. Moreover, when kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Thus, the unique methylation signature of the kidney is degraded, and epigenetic information is lost, when kidney disease progresses. These methylation sites are enriched for specific and methylation-sensitive transcription-factor binding sites, and associated genes show disease-dependent changes in expression. These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines.
The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study
Authors: Wu Jie , Xiao Zhenxu , Wang Mengjing , Wu Wanqing , Ma Xiaoxi , Liang Xiaoniu , Zheng Li , Ding Saineng , Luo Jianfeng , Cao Yang , Hong Zhen , Chen Jing , Zhao Qianhua , Ding Ding 
Published: February 2024

Abstract
Background
The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.

Methods
Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted.

Results
The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = − 0.19, 95% CI − 0.224 to − 0.156, P < 0.001; B = − 0.009, 95% CI − 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = − 0.010, 95% CI − 0.133 to − 0.068, P < 0.001), but not with P-tau181 (B = − 0.003, 95% CI − 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = − 0.790, 95% CI − 1.026 to − 0,554, P < 0.001).

Conclusions
Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.
Guyton perspective in managing peripartum cardiomyopathy patient with pulmonary edema: a case report
Authors: Margaretha Ruth Evlin , George Yohanes W. H. , Hidayat Jefferson 
Published: February 2024

Abstract
Background
Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related condition characterized by left ventricular dysfunction and heart failure, typically occurring in the peripartum period. Individuals with a history of preeclampsia and hypertension are particularly prone to developing PPCM. Recent research suggests that the condition may be triggered by vascular dysfunction influenced by maternal hormones in the late stages of gestation. The onset of left heart failure results in decreased cardiac output, leading to insufficient perfusion, which in turn, contributes to pulmonary edema and exacerbates tissue hypoxia. This cardiovascular response activates the neurohumoral system, causing peripheral vasoconstriction and elevating both mean capillary filling pressure (MCFP) and central venous pressure (CVP). Early administration of furosemide reduces volume overload due to negative cumulative fluid balance gaining and vasodilation, which increases the velocity of intravascular refilling and causes interstitial edema to resolve. This will decrease interstitial fluid pressure, resulting in decreased mechanical compression to systemic capillary and systemic vein pressure, thus decreasing MCFP and CVP subsequently. Reduced CVP also contributes to increased venous return by decreasing the gradient pressure between MCFP and CVP, resulting in increased cardiac output (CO) and improved tissue oxygenation.

Case
A 33-year-old Asian woman, para 3 at full term pregnancy, admitted to the intensive care unit (ICU) after c-section and tubectomy due to shortness of breath and palpitation. Based on history taking, physical examination and echocardiography the patient fulfilled the criteria of PPCM which was also complicated by pulmonary edema. Despite impending respiratory failure, the patient rejected intubation and continuous positive airway pressure (CPAP), and was given oxygen supplementation through nasal cannula. Furosemide was given rapidly continued by maintenance dose and CVP was monitored. Antihypertensive drug, anticoagulants, and bromocriptine were also administered. After achieving negative cumulative fluid balance the patient’s symptoms resolved and was discharged one week later.

Conclusion
There is a correlation between negative cumulative fluid balance and reduced central venous pressure after early furosemide therapy. Suspicion for PPCM should not be lowered in the presence of preeclampsia, it could delay appropriate treatment and increase the mortality.
Determining cost-efficient controls of electrical energy storages using dynamic programming
Authors: Stiglmayr Michael , Uhlemeyer Svenja , Uhlemeyer Björn , Zdrallek Markus 
Published: February 2024

AbstractVolatile electrical energy prices are a challenge and an opportunity for small and medium-sized companies in energy-intensive industries. By using electrical energy storage and/or an adaptation of production processes, companies can significantly profit from time-depending energy prices and reduce their energy costs.We consider a time-discrete optimal control problem to reach a desired final state of the energy storage at a certain time step. Thereby, the energy input is discrete since only multiples of 100 kWh can be purchased at the EPEX SPOT market. We use available price estimates to minimize the total energy cost by a rounding based dynamic programming approach. With our model non-linear energy loss functions of the storage can be considered and we obtain a significant speed-up compared to the integer (linear) programming formulation.
Ecological, financial, social and societal motives for cooperative energy prosumerism: measuring preference heterogeneity in a Belgian energy cooperative
Authors: van Klingeren Fijnanda , De Moor Tine 
Published: February 2024

Abstract
Background
Energy cooperatives in Europe have become more prominent due to the growing interest in and development of renewable energy sources. Cooperatives are often seen as an instrument in the transition to a low-carbon future. The cooperative prosumer is gaining importance, taking on the role of both consumer and producer by setting up and joining electricity cooperatives as investors, shareholders and clients. As is the case with other cooperatives and social enterprises, there are tensions and trade-offs to be made between social, ecological and financial goals. To navigate these tensions and to work towards becoming a resilient institution, it is important that cooperatives preserve their support base made up of their members, who are both clients and shareholders. This study investigates the preference heterogeneity and motivations of members of a large energy cooperative in Belgium, by using stated-choice data from a Discrete Choice Experiment in combination with self-reported membership motives.

Results
Despite the significant presence of member preferences for participation and democratic voting rights, the financial and above all the ecological motives seem to be most important for being a member of the energy cooperative. Based on the stated-choice data, we classify three member types: the financial, the ecological and the social–societal member type. We find a small discrepancy in motives between members who joined early and members who joined later. Where early members care most about ecological aspects, members who joined later have more societal and financial considerations. In terms of effect size and willingness to pay per kilowatt hour, ecological motives prove to be by far the most important factor for cooperative energy prosumers in our sample. In addition, the latent-class analysis shows that over half of the member sample belongs to the ecological motives class.

Conclusions
Preference heterogeneity is present to an extent, but there is an overarching preference for sustainability. Though, cooperatives should be aware that their legal form may not be the only factor that drives membership. Rather, keeping high levels of renewable energy, competitive pricing and being an interesting investment opportunity may be key to cooperatives’ resilience and further development on the energy market.