bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Architecture of Hybrid Male Sterility in a Species Without Sex Chromosomes (Tigriopus californicus, Copepoda: Harpacticoida)
Authors: Olsen Kevin C , Lima Thiago G , Barreto Felipe S , Burton Ronald S 
Published: June 2023

Abstract
Sterility among hybrids is one of the most prevalent forms of reproductive isolation delineating species boundaries and is expressed disproportionately in heterogametic XY males. While hybrid male sterility (HMS) due to the “large X effect” is a well-recognized mechanism of reproductive isolation, it is less clear how HMS manifests in species that lack heteromorphic sex chromosomes. We evaluated differences in allele frequencies at approximately 460,000 SNPs between fertile and sterile F2 interpopulation male hybrids to characterize the genomic architecture of HMS in a species without sex chromosomes (Tigriopus californicus). We tested associations between HMS and mitochondrial-nuclear and/or nuclear-nuclear signatures of incompatibility. Genomic regions associated with HMS were concentrated on a single chromosome with the same primary 2-Mbp regions identified in one pair of reciprocal crosses. Gene Ontology analysis revealed that annotations associated with spermatogenesis were the most overrepresented within the implicated region, with nine protein-coding genes connected with this process found in the quantitative trait locus of chromosome 2. Our results indicate that a narrow genomic region was associated with the sterility of male hybrids in T. californicus and suggest that incompatibilities among select nuclear loci may replace the large X effect when sex chromosomes are absent.
Continuous, but not intermittent, regimens of hypoxia prevent and reverse ataxia in a murine model of Friedreich’s ataxia
Authors: Ast Tslil , Wang Hong , Marutani Eizo , Nagashima Fumiaki , Malhotra Rajeev , Ichinose Fumito , Mootha Vamsi K 
Published: June 2023

AbstractFriedreich’s ataxia (FA) is a devastating, multi-systemic neurodegenerative disease affecting thousands of people worldwide. We previously reported that oxygen is a key environmental variable that can modify FA pathogenesis. In particular, we showed that chronic, continuous normobaric hypoxia (11% FIO2) prevents ataxia and neurological disease in a murine model of FA, although it did not improve cardiovascular pathology or lifespan. Here, we report the pre-clinical evaluation of seven ‘hypoxia-inspired’ regimens in the shFxn mouse model of FA, with the long-term goal of designing a safe, practical and effective regimen for clinical translation. We report three chief results. First, a daily, intermittent hypoxia regimen (16 h 11% O2/8 h 21% O2) conferred no benefit and was in fact harmful, resulting in elevated cardiac stress and accelerated mortality. The detrimental effect of this regimen is likely owing to transient tissue hyperoxia that results when daily exposure to 21% O2 combines with chronic polycythemia, as we could blunt this toxicity by pharmacologically inhibiting polycythemia. Second, we report that more mild regimens of chronic hypoxia (17% O2) confer a modest benefit by delaying the onset of ataxia. Third, excitingly, we show that initiating chronic, continuous 11% O2 breathing once advanced neurological disease has already started can rapidly reverse ataxia. Our studies showcase both the promise and limitations of candidate hypoxia-inspired regimens for FA and underscore the need for additional pre-clinical optimization before future translation into humans.
Framing Positive Obligations under the European Convention on Human Rights Law: Mediating between the Abstract and the Concrete
Authors: Stoyanova Vladislava 
Published: June 2023

Abstract
Positive obligations under the European Convention on Human Rights can be framed with different levels of concreteness. The level chosen is essential for understanding the analytical distinction between the existence of an obligation and its breach. The level of concreteness is an important conceptual framework because it has an impact even on the possibility of making an assessment as to whether the State has breached the obligation, and on how this assessment is performed in the reasoning. Kurt v Austria is used to illustrate how positive obligations can be framed both in more abstract and concrete terms, and how the reasoning mediates between the two. The more it tilts towards a concrete formulation of the obligation, the more the Court appears to assume the role of a rule-maker, which is in tension with the principle that States have discretion as to the concrete measures to fulfill their positive obligations.
Minimum Wages Directive and Beyond: Workers’ Dignity Taken (Almost) Seriously
Authors: Di Marco Antonio 
Published: June 2023

Abstract
This study argues that the Minimum Wages Directive reveals a shift in the Union’s political-economic approach to the social competition in the Single Market, which introduces a creeping extension of the Treaty’s scope and a potential enlargement of the Union’s competences on social matters. While representing a timid starting point for the right to a minimum wage protection, it recognises that the dumping wages phenomena are partly triggered by an (unresolved) structural legal vacuum. By analysing the instrumental function of the fair remuneration towards human dignity, the idea of the right to fair and just working conditions as an open scoped right is advanced; the thesis of a general Union competence on working conditions is finally proposed. The aim is to illustrate what limits and perspectives the European upward social convergence is currently facing, and to what extent the Union is not necessarily a mere reflection of market completion interests.
Judicial Activism and Judge-Made Law at the ECtHR
Authors: Bošnjak Marko , Zajac Kacper 
Published: June 2023

Abstract
This paper contributes to an ongoing debate concerning the perceived judicial activism of the European Court of Human Rights (ECtHR). It argues that the output of the Court should be better viewed as the phenomenon of judicial law-making, not unlike in domestic jurisdictions. However, unlike many domestic legal systems, the European Convention on Human Rights framework promotes large quantities of judge-made law. This outcome results from a combination of objective factors that, taken together, enhance the process of judicial law-making by the ECtHR. Those factors include the applied mode of interpretation of the Convention, the approach to its construction, the weak textual basis, the existence of positive obligations, the lack of the doctrine of precedent, the extremely high case law and judicial turnovers, the concurrent legislative inactivity, the existence of the inter-state jurisdiction and the doctrine of autonomous meaning. At the same time, the judicial law-making is only hindered by the doctrine of subsidiarity, the principle of margin of appreciation and the Fourth Instance doctrine. As a consequence of this overwhelming dominance of the factors enhancing the process of judicial law-making over those that hinder it, the ECtHR produces large quantities of judge-made law.
Developing electronic clinical quality measures to assess the cancer diagnostic process
Authors: Murphy Daniel R , Zimolzak Andrew J , Upadhyay Divvy K , Wei Li , Jolly Preeti , Offner Alexis , Sittig Dean F , Korukonda Saritha , Rekha Riyaa Murugaesh , Singh Hardeep 
Published: June 2023

Abstract

Objective
Measures of diagnostic performance in cancer are underdeveloped. Electronic clinical quality measures (eCQMs) to assess quality of cancer diagnosis could help quantify and improve diagnostic performance.

Materials and Methods
We developed 2 eCQMs to assess diagnostic evaluation of red-flag clinical findings for colorectal (CRC; based on abnormal stool-based cancer screening tests or labs suggestive of iron deficiency anemia) and lung (abnormal chest imaging) cancer. The 2 eCQMs quantified rates of red-flag follow-up in CRC and lung cancer using electronic health record data repositories at 2 large healthcare systems. Each measure used clinical data to identify abnormal results, evidence of appropriate follow-up, and exclusions that signified follow-up was unnecessary. Clinicians reviewed 100 positive and 20 negative randomly selected records for each eCQM at each site to validate accuracy and categorized missed opportunities related to system, provider, or patient factors.

Results
We implemented the CRC eCQM at both sites, while the lung cancer eCQM was only implemented at the VA due to lack of structured data indicating level of cancer suspicion on most chest imaging results at Geisinger. For the CRC eCQM, the rate of appropriate follow-up was 36.0% (26 746/74 314 patients) in the VA after removing clinical exclusions and 41.1% at Geisinger (1009/2461 patients; P &lt; .001). Similarly, the rate of appropriate evaluation for lung cancer in the VA was 61.5% (25 166/40 924 patients). Reviewers most frequently attributed missed opportunities at both sites to provider factors (84 of 157).

Conclusions
We implemented 2 eCQMs to evaluate the diagnostic process in cancer at 2 large health systems. Health care organizations can use these eCQMs to monitor diagnostic performance related to cancer.
Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
Authors: Feng Xiaoshuang , Wu Wendy Yi-Ying , Onwuka Justina Ucheojor , Haider Zahra , Alcala Karine , Smith-Byrne Karl , Zahed Hana , Guida Florence , Wang Renwei , Bassett Julie K , Stevens Victoria , Wang Ying , Weinstein Stephanie , Freedman Neal D , Chen Chu , Tinker Lesley , Nøst Therese Haugdahl , Koh Woon-Puay , Muller David , Colorado-Yohar Sandra M , Tumino Rosario , Hung Rayjean J , Amos Christopher I , Lin Xihong , Zhang Xuehong , Arslan Alan A , Sánchez Maria-Jose , Sørgjerd Elin Pettersen , Severi Gianluca , Hveem Kristian , Brennan Paul , Langhammer Arnulf , Milne Roger L , Yuan Jian-Min , Melin Beatrice , Johansson Mikael , Robbins Hilary A , Johansson Mattias 
Published: June 2023

Abstract

Background
We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.

Methods
We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models’ sensitivity. All tests were 2-sided.

Results
The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.

Conclusion
Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
Disparities in parental distress in a multicenter clinical trial for pediatric acute lymphoblastic leukemia
Authors: Umaretiya Puja J , Koch Victoria B , Flamand Yael , Aziz-Bose Rahela , Ilcisin Lenka , Valenzuela Ariana , Cole Peter D , Gennarini Lisa M , Kahn Justine M , Kelly Kara M , Tran Thai Hoa , Michon Bruno , Welch Jennifer J G , Wolfe Joanne , Silverman Lewis B , Bona Kira 
Published: June 2023

Abstract

Background
Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001.

Methods
This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status.

Results
Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1.

Conclusions
Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents—compared with unexposed parents—experienced statistically significantly increased odds of severe psychological distress at the time of their child’s leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being.
Recapture Results and Classical Logic
Authors: Fiore Camillo , Rosenblatt Lucas 
Published: June 2023

AbstractAn old and well-known objection to non-classical logics is that they are too weak; in particular, they cannot prove a number of important mathematical results. A promising strategy to deal with this objection consists in proving so-called recapture results. Roughly, these results show that classical logic can be used in mathematics and other unproblematic contexts. However, the strategy faces some potential problems. First, typical recapture results are formulated in a purely logical language, and do not generalize nicely to languages containing the kind of vocabulary that usually motivates non-classical theories—for example, a language containing a naive truth predicate. Second, proofs of recapture results typically employ classical principles that are not valid in the targeted non-classical system; hence non-classical theorists do not seem entitled to those results. In this paper we analyse these problems and provide solutions on behalf of non-classical theorists. To address the first problem, we provide a novel kind of recapture result, which generalizes nicely to a truth-theoretic language. As for the second problem, we argue that it relies on an ambiguity, and that once the ambiguity is removed there are no reasons to think that non-classical logicians are not entitled to their recapture results.
Minute-cadence observations of the LAMOST fields with the TMTS – III. Statistical study of the flare stars from the first two years
Authors: Liu Qichun , Lin Jie , Wang Xiaofeng , Gu Shenghong , Shi Jianrong , Zhang Liyun , Xi Gaobo , Mo Jun , Cai Yongzhi , Chen Liyang , Chen Zhihao , Guo Fangzhou , Jiang Xiaojun , Li Gaici , Li Wenxiong , Lin Han , Lin Weili , Liu Jialian , Miao Cheng , Ma Xiaoran , Peng Haowei , Xiang Danfeng , Yan Shengyu , Zhang Jicheng , Zhang Xinhan 
Published: June 2023

ABSTRACTTsinghua University-Ma Huateng Telescopes for Survey (TMTS) aims to detect fast-evolving transients in the Universe, which has led to the discovery of thousands of short-period variables and eclipsing binaries since 2020. In this paper, we present the observed properties of 125 flare stars identified by TMTS within the first two years, with an attempt to constrain their eruption physics. As expected, most of these flares were recorded in late-type red stars with GBP − GRP &gt;2.0 mag; however, the flares associated with bluer stars tend to be on average more energetic and have broader profiles. The peak flux (Fpeak) of the flare is found to depend strongly on the equivalent duration (ED) of the energy release, i.e. Fpeak∝ED0.72 ± 0.04, which is consistent with results derived from the Kepler and Evryscope samples. This relation is likely to be related to the magnetic loop emission, while, for the more popular non-thermal electron heating model, a specific time evolution may be required to generate this relation. We notice that flares produced by hotter stars have a flatter Fpeak - ED relation compared to that from cooler stars. This is related to the statistical discrepancy in light-curve shape of flare events with different colours. In spectra from LAMOST, we find that flare stars have apparently stronger H α emission than inactive stars, especially at the low-temperature end, suggesting that chromospheric activity plays an important role in producing flares. On the other hand, the subclass with frequent flares is found to show H α emission of similar strength in its spectra to that recorded with only a single flare but similar effective temperature, implying that chromospheric activity may not be the only trigger for eruptions.
ARMADiLLO: a web server for analyzing antibody mutation probabilities
Authors: Martin Beem Joshua S , Venkatayogi Sravani , Haynes Barton F , Wiehe Kevin 
Published: June 2023

Abstract
Antibodies are generated by B cells that evolve receptor specificity to pathogens through rounds of mutation and selection in a process called affinity maturation. Somatic hypermutation is mediated by an enzyme with DNA sequence context-dependent targeting and substitution resulting in variable probabilities of amino acid substitutions during affinity maturation. We have previously developed a program called Antigen Receptor Mutation Analyzer for the Detection of Low Likelihood Occurrences (ARMADiLLO) that performs simulations of the somatic hypermutation process to estimate the probabilities of observed antibody mutations. Here we describe the ARMADiLLO web server (https://armadillo.dhvi.duke.edu), an easy-to-use web interface that analyzes input antibody sequences and displays the probability estimates for all possible amino acid changes over the full length of an antibody sequence. The probability of antibody mutations can be used by immunologists studying B cell ontogenies and by vaccine designers that are pursuing strategies to elicit broadly neutralizing antibodies which are enriched with developmentally rate-limiting improbable mutations. The ARMADiLLO web server also contains precomputed results reporting the probability of amino acid substitutions in all human V gene segments and in a collection of HIV broadly neutralizing antibodies.
A method to generate capture baits for targeted sequencing
Authors: Sundararaman Balaji , Vershinina Alisa O , Hershauer Samantha , Kapp Joshua D , Dunn Shelby , Shapiro Beth , Green Richard E 
Published: June 2023

Abstract
Hybridization capture approaches allow targeted high-throughput sequencing analysis at reduced costs compared to shotgun sequencing. Hybridization capture is particularly useful in analyses of genomic data from ancient, environmental, and forensic samples, where target content is low, DNA is fragmented and multiplex PCR or other targeted approaches often fail. Here, we describe a DNA bait synthesis approach for hybridization capture that we call Circular Nucleic acid Enrichment Reagent, or CNER (pronounced ‘snare’). The CNER method uses rolling-circle amplification followed by restriction digestion to discretize microgram quantities of hybridization probes. We demonstrate the utility of the CNER method by generating probes for a panel of 23 771 known sites of single nucleotide polymorphism in the horse genome. Using these probes, we capture and sequence from a panel of ten ancient horse DNA libraries, comparing CNER capture efficiency to a commercially available approach. With about one million read pairs per sample, CNERs captured more targets (90.5% versus 66.5%) at greater mean depth than an alternative commercial approach.
Reserved gait capacity and mortality among patients undergoing hemodialysis
Authors: Yoshikoshi Shun , Yamamoto Shohei , Suzuki Yuta , Imamura Keigo , Harada Manae , Kamiya Kentaro , Matsunaga Atsuhiko 
Published: June 2023

ABSTRACT

Background
Patients undergoing hemodialysis (HD) have difficulty increasing their gait speed in daily life. The extent of the increase from the usual gait speed (UGS) to the maximum gait speed (MGS) is considered the reserved gait capacity (RGC). Little is known regarding the implications of RGC. This study aimed to investigate the association between RGC and all-cause mortality in patients undergoing HD.

Methods
In this retrospective study, we assessed the usual and maximum 10-m walking speed of outpatients who underwent HD between October 2002 and August 2021. RGC was defined as the ratio of MGS to UGS. Patients were divided into three groups according to the tertiles of RGC (low, moderate and high). A Cox proportional hazards regression model was used to examine the association between RGC and all-cause mortality.

Results
Of the 496 (median age 66.0 years; men 59%) participants, 186 patients died during the follow-up (incident ratio of 62.0 per 1000 person-years). The patients with moderate [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46–0.94] and high (HR 0.44, 95% CI 0.30–0.65) RGC had a lower risk of mortality than the low RGC group. Furthermore, even when restricted to a population with only UGS &lt;1.0 m/s, the group with high RGC still had a lower risk of mortality than those with low RGC (HR 0.55, 95% CI 0.33–0.94).

Conclusions
Lower RGC was independently associated with an increased risk of all-cause mortality among patients on HD; high RGC had a survival advantage even with a slow UGS.
Axes and polarities in leaf vein formation
Authors: Scarpella Enrico 
Published: June 2023

AbstractFor multicellular organisms to develop, cells must grow, divide, and differentiate along preferential or exclusive orientations or directions. Moreover, those orientations, or axes, and directions, or polarities, must be coordinated between cells within and between tissues. Therefore, how axes and polarities are coordinated between cells is a key question in biology. In animals, such coordination mainly depends on cell migration and direct interaction between proteins protruding from the plasma membrane. Both cell movements and direct cell–cell interactions are prevented in plants by cell walls that surround plant cells and keep them apart and in place. Therefore, plants have evolved unique mechanisms to coordinate their cell axes and polarities. Here I will discuss evidence suggesting that understanding how leaf veins form may uncover those unique mechanisms. Indeed, unlike previously thought, the cell-to-cell polar transport of the plant hormone auxin along developing veins cannot account for many features of vein patterning. Instead, those features can be accounted for by models of vein patterning that combine polar auxin transport with auxin diffusion through plasmodesmata along the axis of developing veins. Though it remains unclear whether such a combination of polar transport and axial diffusion of auxin can account for the formation of the variety of vein patterns found in plant leaves, evidence suggests that such a combined mechanism may control plant developmental processes beyond vein patterning.