bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common and Rare Variants in TMEM175 Gene Concur to the Pathogenesis of Parkinson’s Disease in Italian Patients
Authors: Palomba Nicole Piera , Fortunato Giorgio , Pepe Giuseppe , Modugno Nicola , Pietracupa Sara , Damiano Immacolata , Mascio Giada , Carrillo Federica , Di Giovannantonio Luca Giovanni , Ianiro Laura , Martinello Katiuscia , Volpato Viola , Desiato Vincenzo , Acri Riccardo , Storto Marianna , Nicoletti Ferdinando , Webber Caleb , Simeone Antonio , Fucile Sergio , Maglione Vittorio , Esposito Teresa 
Published: January 2023

AbstractParkinson’s disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused the attention on the common and rare variants identified in the lysosomal K+ channel TMEM175. The study includes a detailed clinical and genetic analysis of 400 cases and 300 controls. Molecular studies were performed on patient-derived fibroblasts. The functional properties of the mutant channels were assessed by patch-clamp technique and co-immunoprecipitation. We have found that TMEM175 was highly expressed in dopaminergic neurons of the substantia nigra pars compacta and in microglia of the cerebral cortex of the human brain. Four common variants were associated with PD, including two novel variants rs2290402 (c.-10C > T) and rs80114247 (c.T1022C, p.M341T), located in the Kozak consensus sequence and TM3II domain, respectively. We also disclosed 13 novel highly penetrant detrimental mutations in the TMEM175 gene associated with PD. At least nine of these mutations (p.R35C, p. R183X, p.A270T, p.P308L, p.S348L, p. L405V, p.R414W, p.P427fs, p.R481W) may be sufficient to cause the disease, and the presence of mutations of other genes correlated with an earlier disease onset. In vitro functional analysis of the ion channel encoded by the mutated TMEM175 gene revealed a loss of the K+ conductance and a reduced channel affinity for Akt. Moreover, we observed an impaired autophagic/lysosomal proteolytic flux and an increase expression of unfolded protein response markers in patient-derived fibroblasts. These data suggest that mutations in TMEM175 gene may contribute to the pathophysiology of PD.
Genetic landscape and immune mechanism of monocytes associated with the progression of acute-on-chronic liver failure
Authors: Yao Jia , Liu Tian , Zhao Qiang , Ji Yaqiu , Bai Jinjia , Wang Han , Yao Ruoyu , Zhou Xiaoshuang , Chen Yu , Xu Jun 
Published: January 2023

Abstract
Objective
Acute-on-chronic liver failure (ACLF) has a high prevalence and short-term mortality. Monocytes play an important role in the development of ACLF. However, the monocyte subpopulations with unique features and functions in ACLF and associated with disease progression remain poorly understood. We investigated the specific monocyte subpopulations associated with ACLF progression and their roles in inflammatory responses using the single-cell RNA sequencing (scRNA-seq).

Methods
We performed scRNA-seq on 17,310 circulating monocytes from healthy controls and ACLF patients and genetically defined their subpopulations to characterize specific monocyte subpopulations associated with ACLF progression.

Results
Five monocyte subpopulations were obtained, including pro-inflammatory monocytes, CD16 monocytes, HLA monocytes, megakaryocyte-like monocytes, and NK-like monocytes. Comparisons of the monocytes between ACLF patients and healthy controls showed that the pro-inflammatory monocytes had the most significant gene changes, among which the expressions of genes related to inflammatory responses and cell metabolism were significantly increased while the genes related to cell cycle progression were significantly decreased. Furthermore, compared with the ACLF survival group, the ACLF death group had significantly higher expressions of pro-inflammatory cytokines (e.g., IL-6) and their receptors, chemokines (e.g., CCL4 and CCL5), and inflammation-inducing factors (e.g., HES4). Additionally, validation using scRNA-seq and flow cytometry revealed the presence of a cell type-specific transcriptional signature of pro-inflammatory monocytes THBS1, whose production might reflect the disease progression and poor prognosis.

Conclusions
We present the accurate classification, molecular markers, and signaling pathways of monocytes associated with ACLF progression. Therapies targeting pro-inflammatory monocytes may be a promising approach for blocking ACLF progression.
Decision-making performance and self-generated knowledge in handball-defense patterns: a case of representational redescription
Authors: Magnaguagno Lukas , Hossner Ernst-Joachim , Schmid Jürg , Zahno Stephan 
Published: January 2023

AbstractIn sport games, perceptual–cognitive skills are discussed as a decisive aspect of players’ expertise. However, an understanding of the relationship between these skills and actual game performance is limited, particularly, regarding the role of pattern identification and situational-probability estimation in performance. The present study thus aimed to examine how identification of teammates’ defensive qualities relates to decision-making performance in a 3:3 virtual-reality defensive task. Examining data collected in two previously published studies, we analyzed the relationship between explicit pattern detection and response correctness, and also as a function of players’ experience. Experience was operationalized as either expertise level (Experiment 1) or task-specific experience (Experiment 2). As expected, the explicit detection of a game-specific pattern was found to be facilitated by experience. However, the results imply that it is accumulated experience that enhances decision-making performance rather than the degree of self-generated explicit knowledge. This finding supports the notion of “representational redescription” as introduced by Karmiloff-Smith (1994). For sports practice, this suggests that the pattern identification demonstrated by skilled athletes should not be overestimated as a predictor of game performance, while the explicit provision of knowledge might be beneficial for less-skilled athletes, particularly in situations of high uncertainty.
Sustainability assessment in innovation design processes: place, role, and conditions of use in agrifood systems. A review
Authors: Perrin Aurélie , Yannou-Le Bris Gwenola , Angevin Frédérique , Pénicaud Caroline 
Published: January 2023

AbstractFacing the ecological and social crisis that the agrifood systems cross, a profound transformation of food systems is required, necessitating systemic and sustainable innovations. Sustainability assessments are generally performed to identify and/or validate the improvement in sustainability conferred by a designed artifact relative to the current or standard situation. However, they can have many other benefits in the design process. Here, we review the place, role, and conditions of use of sustainability assessment in innovation design processes in agrifood systems. By cross-referencing published findings and our own experience, we formalize a design process highlighting the place of sustainability assessment, whether design is intended for the creation of an agricultural or food artifact. We identify three types of assessment: initial diagnosis, screening between solutions at the ideation stage, and evaluation at the prototyping and development stages. We discuss ways of performing each of these assessments and highlight general key points about sustainability assessment. A first set of key points relate to criteria and indicators, a second set to the role of stakeholders, a third one to the adaptive nature of the assessment, and the last one to the uncertainty consideration. These key points provide guidance for efficient assessment in the design of innovations to increase the sustainability of agrifood systems. Thus, we demonstrate that the design process of innovations for sustainable agrifood systems requires (1) to formalize the place and mode of assessment, (2) to make use of relevant sustainability criteria and indicators, (3) to reinforce participatory practices, and (4) to adapt the assessment to the context of the designed artifact, to facilitate choices between imperfect solutions. Such an approach aims to promote innovations that meet the expectations of the system’s direct stakeholders, but also integrate the needs of invisible actors such as the environment or the well-being of populations.
Optimizing reflex urine cultures: Using a population-specific approach to diagnostic stewardship
Authors: Advani Sonali D. , Turner Nicholas A. , Schmader Kenneth E. , Wrenn Rebekah H. , Moehring Rebekah W. , Polage Christopher R. , Vaughn Valerie M. , Anderson Deverick J. 
Published: January 2023

AbstractBackground:Clinicians and laboratories routinely use urinalysis (UA) parameters to determine whether antimicrobial treatment and/or urine cultures are needed. Yet the performance of individual UA parameters and common thresholds for action are not well defined and may vary across different patient populations.Methods:In this retrospective cohort study, we included all encounters with UAs ordered 24 hours prior to a urine culture between 2015 and 2020 at 3 North Carolina hospitals. We evaluated the performance of relevant UA parameters as potential outcome predictors, including sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria and used receiver operating curves to identify the 5 best-performing models for predicting significant bacteriuria (≥100,000 colony-forming units of bacteria/mL).Results:In 221,933 encounters during the 6-year study period, no single UA parameter had both high sensitivity and high specificity in predicting bacteriuria. Absence of leukocyte esterase and pyuria had a high NPV for significant bacteriuria. Combined UA parameters did not perform better than pyuria alone with regard to NPV. The high NPV ≥0.90 of pyuria was maintained among most patient subgroups except females aged ≥65 years and patients with indwelling catheters.Conclusion:When used as a part of a diagnostic workup, UA parameters should be leveraged for their NPV instead of sensitivity. Because many laboratories and hospitals use reflex urine culture algorithms, their workflow should include clinical decision support and or education to target symptomatic patients and focus on populations where absence of pyuria has high NPV.
THE DIAGONAL STRONG REFLECTION PRINCIPLE AND ITS FRAGMENTS
Authors: COX SEAN D. , FUCHS GUNTER 
Published: January 2023

AbstractA diagonal version of the strong reflection principle is introduced, along with fragments of this principle associated with arbitrary forcing classes. The relationships between the resulting principles and related principles, such as the corresponding forcing axioms and the corresponding fragments of the strong reflection principle, are analyzed, and consequences are presented. Some of these consequences are “exact” versions of diagonal stationary reflection principles of sets of ordinals. We also separate some of these diagonal strong reflection principles from related axioms.
On parabolic subgroups of symplectic reflection groups
Authors: Bellamy Gwyn , Schmitt Johannes , Thiel Ulrich 
Published: January 2023

AbstractUsing Cohen’s classification of symplectic reflection groups, we prove that the parabolic subgroups, that is, stabilizer subgroups, of a finite symplectic reflection group, are themselves symplectic reflection groups. This is the symplectic analog of Steinberg’s Theorem for complex reflection groups.Using computational results required in the proof, we show the nonexistence of symplectic resolutions for symplectic quotient singularities corresponding to three exceptional symplectic reflection groups, thus reducing further the number of cases for which the existence question remains open.Another immediate consequence of our result is that the singular locus of the symplectic quotient singularity associated to a symplectic reflection group is pure of codimension two.
The Virtues of Interpretable Medical AI
Authors: Hatherley Joshua , Sparrow Robert , Howard Mark 
Published: January 2023

AbstractArtificial intelligence (AI) systems have demonstrated impressive performance across a variety of clinical tasks. However, notoriously, sometimes these systems are “black boxes.” The initial response in the literature was a demand for “explainable AI.” However, recently, several authors have suggested that making AI more explainable or “interpretable” is likely to be at the cost of the accuracy of these systems and that prioritizing interpretability in medical AI may constitute a “lethal prejudice.” In this paper, we defend the value of interpretability in the context of the use of AI in medicine. Clinicians may prefer interpretable systems over more accurate black boxes, which in turn is sufficient to give designers of AI reason to prefer more interpretable systems in order to ensure that AI is adopted and its benefits realized. Moreover, clinicians may be justified in this preference. Achieving the downstream benefits from AI is critically dependent on how the outputs of these systems are interpreted by physicians and patients. A preference for the use of highly accurate black box AI systems, over less accurate but more interpretable systems, may itself constitute a form of lethal prejudice that may diminish the benefits of AI to—and perhaps even harm—patients.
Multiple Auroral Streamer Bundles in Conjugate Hemispheres and Multiple Near‐Earth Injections
Authors: Tian S. , Wang C.‐P. , Lyons L. R. , Bortnik J. , Weygand J. M. , Liu J. , Yadav S. , Ma Q. , Reeves G. D. , Henderson M. G. , Wolf R. A. 
Published: January 2023

AbstractThe auroral streamer is a type of auroral form commonly observed during geomagnetic substorms. Previous studies suggested a coupling between auroral streamers and channels of bursty bulk flows in the plasma sheet. However, whether one flow channel can map to multiple streamers is unclear. Here, we present an event containing consecutive auroral streamer subevents. The event features similar spatial and temporal development of auroral streamers in conjugate hemispheres. In most of the subevents, we observed that what an in‐space auroral camera saw as one streamer actually consisted of multiple streamers (i.e., a streamer bundle). A coordinated analysis of near‐earth injections and ionospheric currents suggests that one overall flow channel (or bubble) can map to a streamer bundle. Multiple streamer bundles and thus multiple overall flow channels can occur simultaneously at different local times. Evidence supports that the overall flow channel may consist of or split into several narrower flow channels and each maps to a streamer and causes a particle injection.
Basin‐Scale CO2 Emissions From the East River in South China: Importance of Small Rivers, Human Impacts and Monsoons
Authors: Liu Boyi , Wang Zifeng , Tian Mingyang , Yang Xiankun , Chan Chun Ngai , Chen Shuai , Yang Qianqian , Ran Lishan 
Published: January 2023

AbstractRiverine carbon dioxide (CO2) emissions are an essential component of the riverine carbon cycle, but an accurate assessment of riverine CO2 emission fluxes is still hindered by the spatial and temporal variations among river basins caused by differences in climate, watershed characteristics, and human activity. Here, we evaluate the riverine CO2 flux from the subtropical East River Basin (ERB) in south China, a region strongly affected by monsoon climate and anthropogenic land use changes. Our results suggest small rivers are major contributors to riverine CO2 emissions, even with relatively low CO2 concentrations and small water surface areas (SAs). They contribute disproportionately to 74.4% of the total fluxes due to high gas transfer velocity (k) across the water‐air interface. Land use changes have substantially enhanced CO2 emissions from river networks. Normalized areal riverine CO2 fluxes in the urban‐ and cropland‐dominated Middle and Lower ERB (27.6 and 39.4 g C m−2 yr−1) were two and three times higher than the 9.1 g C m−2 yr−1 in the forest‐dominated Upper ERB. Due to the larger water SA and higher k caused by monsoon‐induced precipitation, the East River acts as a stronger carbon source during the wet season, emitting 0.67 Tg C yr−1 to the atmosphere, which is about twice that during the dry season (0.33 Tg C yr−1). Our study illustrated how monsoon climate and land use in the ERB have regulated its riverine CO2 emissions. Our findings also provided valuable insights into the role of small rivers in the basin‐wide carbon cycle.
Sex and gender in hypertension guidelines
Authors: Meinert Fabian , Thomopoulos Costas , Kreutz Reinhold 
Published: January 2023

AbstractThis paper reviews 11 current and previous international and some selected national hypertension guidelines regarding sex and gender-related differences. Those differences can be attributed to biological sex and to gender differences that are determined by socially constructed norms. All reviewed guidelines agree on a higher hypertension prevalence in men than in women. They also concur that evidence does not support different blood pressure thresholds and targets for treatment between men and women. Differences refer in addition to the differences in epidemiological aspects to differences in some morphometric diagnostic indices, e.g., left ventricular mass or the limits for daily alcohol intake. Concerning practical management, there are hardly any clear statements on different procedures that go beyond the consensus that blockers of the renin–angiotensin system should not be used in women of childbearing age wishing to become pregnant. Some further sex-specific aspects are related to differences in tolerability or drug-specific side effects of BP-lowering drugs. There is also a consensus about the need for blood pressure monitoring before and during the use of contraceptive pills. For management of pregnancy, several guidelines still recommend no active treatment in pregnant women without severe forms of hypertension, despite a wide consensus about the definition of hypertension in pregnancy. A disparity in treatment targets when treating severe and non-severe hypertension in pregnancy is also observed. Overall, sex-specific aspects are only very sparsely considered or documented in the evaluated guidelines highlighting an unmet need for future clinical research on this topic.
Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5
Authors: Wang Yanqun , Yan An , Song Deyong , Dong Chuangchuang , Rao Muding , Gao Yuanzhu , Qi Ruxi , Ma Xiaomin , Wang Qiaoping , Xu Hongguang , Liu Hong , Han Jing , Duan Maoqin , Liu Shuo , Yu Xiaoping , Zong Mengqi , Feng Jianxia , Jiao Jie , Zhang Huimin , Li Min , Yu Beibei , Wang Yanxia , Meng Fanhao , Ni Xiaodan , Li Ying , Shen Zhenduo , Sun Baiping , Shao Xin , Zhao Haifeng , Zhao Yanyan , Li Rui , Zhang Yanan , Du Guangying , Lu Jun , You Chunna , Jiang Hua , Zhang Lu , Wang Lan , Dou Changlin , Liu Zheng , Zhao Jincun 
Published: January 2023

AbstractSARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1–BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.
Pressure-induced charge orders and their postulated coupling to magnetism in hexagonal multiferroic LuFe2O4
Authors: Liu Fengliang , Hao Yiqing , Ni Jinyang , Zhao Yongsheng , Zhang Dongzhou , Fabbris Gilberto , Haskel Daniel , Cheng Shaobo , Xu Xiaoshan , Yin Lifeng , Xiang Hongjun , Zhao Jun , Lü Xujie , Wang Wenbin , Shen Jian , Yang Wenge 
Published: January 2023

AbstractHexagonal LuFe2O4 is a promising charge order (CO) driven multiferroic material with high charge and spin-ordering temperatures. The coexisting charge and spin orders on Fe3+/Fe2+ sites result in magnetoelectric behaviors, but the coupling mechanism between the charge and spin orders remains elusive. Here, by tuning external pressure, we reveal three charge-ordered phases with suggested correlation to magnetic orders in LuFe2O4: (i) a centrosymmetric incommensurate three-dimensional CO with ferrimagnetism, (ii) a non-centrosymmetric incommensurate quasi-two-dimensional CO with ferrimagnetism, and (iii) a centrosymmetric commensurate CO with antiferromagnetism. Experimental in situ single-crystal X-ray diffraction and X-ray magnetic circular dichroism measurements combined with density functional theory calculations suggest that the charge density redistribution caused by pressure-induced compression in the frustrated double-layer [Fe2O4] cluster is responsible for the correlated spin-charge phase transitions. The pressure-enhanced effective Coulomb interactions among Fe-Fe bonds drive the frustrated (1/3, 1/3) CO to a less frustrated (1/4, 1/4) CO, which induces the ferrimagnetic to antiferromagnetic transition. Our results not only elucidate the coupling mechanism among charge, spin, and lattice degrees of freedom in LuFe2O4, but also provide a new way to tune the spin-charge orders in a highly controlled manner.
The ‘myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19’ is far from reality
Authors: Dhibar Deba Prasad , Arora Navneet , Chaudhary Deepak , Prakash Ajay , Medhi Bikash , Singla Neeraj , Mohindra Ritin , Suri Vikas , Bhalla Ashish , Sharma Navneet , Singh Mini P. , Lakshmi P. V. M. , Goyal Kapil , Ghosh Arnab 
Published: January 2023

AbstractThe efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.