bluuebunny/crossref_metadata_2025 huggingface dataset:
Presaccadic preview shapes postsaccadic processing more where perception is poor
Authors: Liu Xiaoyi , Melcher David , Carrasco Marisa , Hanning Nina M.
Published: September 2024

The presaccadic preview of a peripheral target enhances the efficiency of its postsaccadic processing, termed the extrafoveal preview effect. Peripheral visual performance—and thus the quality of the preview—varies around the visual field, even at isoeccentric locations: It is better along the horizontal than vertical meridian and along the lower than upper vertical meridian. To investigate whether these polar angle asymmetries influence the preview effect, we asked human participants to preview four tilted gratings at the cardinals, until a central cue indicated which one to saccade to. During the saccade, the target orientation either remained or slightly changed (valid/invalid preview). After saccade landing, participants discriminated the orientation of the (briefly presented) second grating. Stimulus contrast was titrated with adaptive staircases to assess visual performance. Expectedly, valid previews increased participants’ postsaccadic contrast sensitivity. This preview benefit, however, was inversely related to polar angle perceptual asymmetries; largest at the upper, and smallest at the horizontal meridian. This finding reveals that the visual system compensates for peripheral asymmetries when integrating information across saccades, by selectively assigning higher weights to the less-well perceived preview information. Our study supports the recent line of evidence showing that perceptual dynamics around saccades vary with eye movement direction.
A method to observe field-region oxide charge and inter-electrode isolation from CV-characteristics of n-on-p devices
Authors: Abdilov T. , Akchurin N. , Carty C. , Kazhykarim Y. , Kuryatkov V. , Peltola T. , Wade A.
Published: September 2024

N-on-p silicon sensors will be utilized in the Compact
Muon Solenoid (CMS) detector's tracker and High Granularity
Calorimeter (HGCAL) in the High Luminosity upgrade of the Large
Hadron Collider (HL-LHC). Among their several advantages in terms
of radiation hardness over the traditional p-on-n sensors in the
extreme radiation environment of the HL-LHC are electron collection
instead of holes and overlapping maxima of weighting and electric
fields at the charge-collecting electrodes. The disadvantage of the
multi-channel SiO2-passivated n-on-p sensors is the
generation of an inversion layer under the Si/SiO2-interface by a
positive interface-oxide-charge (N
ox) that at high
densities can compromise the position resolution by creating a
conduction channel between the electrodes. This issue is typically
addressed by including additional isolnts (p-stp, p-spray)
between n+-electrodes. Focusing on the guard-ring regions of
n-on-p sensors where no isolation implants are applied between
the electrodes, a capacitance-voltage (CV) characterization study
of both 6-inch wafer test diodes and 8-inch HGCAL prototype and
pre-series sensors showed a distinct threshold voltage
(V
th,iso) in the CV-characteristics of a biased
n+-electrode when its enclosing guard-ring was left
floating. When reproduced by simulations, the measured
V
th,iso was found to contain information on the
field-region N
ox and indicate the threshold where the
two electrodes become electrically isolated by the influence of the
reverse bias voltage. Together with previous studies on the
inter-electrode isolation of irradiated n-on-p sensors, the
results indicate that position sensitive n-on-p sensors without
isolation implants may be feasible in future HEP experiments.
Birational geometry of moduli spaces of sheaves and Bridgeland stability
Authors: Huizenga Jack
Published: September 2024

Moduli spaces of sheaves and Hilbert schemes of points have experienced a recent resurgence in interest in the past several years, due largely to new techniques arising from Bridgeland stability conditions and derived category methods. In particular, classical questions about the birational geometry of these spaces can be answered by using new tools such as the positivity lemma of Bayer and Macrì. In this article we first survey classical results on moduli spaces of sheaves and their birational geometry. We then discuss the relationship between these classical results and the new techniques coming from Bridgeland stability, and discuss how cones of ample divisors on these spaces can be computed with these new methods. This survey expands upon the author’s talk at the 2015 Bootcamp in Algebraic Geometry preceding the 2015 AMS Summer Research Institute on Algebraic Geometry at the University of Utah.
Positive characteristic algebraic geometry
Authors: Patakfalvi Zsolt , Schwede Karl , Tucker Kevin
Published: September 2024

These lecure notes contain a detailed introduction to the recent F-singularity theory methods in positive characteristic algebraic geometry. We carefully define the different local and global notions of F-singularity theory, show how they relate to other notions of algebraic geometry, as well as we include some applications.
Innovating a Community-driven Enumeration and Needs Assessment of People Experiencing Homelessness: A Network Sampling Approach for the HUD-Mandated Point-in-Time Count
Authors: Almquist Zack W , Kahveci Ihsan , Hazel Mary Ashley , Kajfasz Owen , Rothfolk Janelle , Guilmette Claire , Anderson M C , Ozeryansky Larisa , Hagopian Amy
Published: September 2024

To enumerate people experiencing homelessness in the U.S., the federal Department of Housing and Urban Development (HUD) mandates its designated local jurisdictions regularly conduct a crude census of this population. This Point-in-Time (PIT) body count, typically conducted on a January night by volunteers with flashlights and clipboards, is often followed by interviews with a separate convenience sample. Here, we propose employing a network-based (peer-referral) respondent-driven sampling (RDS) method to generate a representative sample of unsheltered people, accompanied by a novel method to generate a statistical estimate of the number of unsheltered people in the jurisdiction. First, we develop a power analysis for the sample size of our RDS survey to count unsheltered people experiencing homelessness. Then, we conducted three large-scale population-representative samples in King County, WA (Seattle metro) in 2022, 2023, and 2024. We describe the data collection and the application of our new method, comparing the 2020 PIT count (the last visual PIT count performed in King County) to the new method 2022 and 2024 PIT counts. We conclude with a discussion and future directions.
DeepIRES: a hybrid deep learning model for accurate identification of internal ribosome entry sites in cellular and viral mRNAs
Authors: Zhao Jian , Chen Zhewei , Zhang Meng , Zou Lingxiao , He Shan , Liu Jingjing , Wang Quan , Song Xiaofeng , Wu Jing
Published: September 2024

The internal ribosome entry site (IRES) is a cis-regulatory element that can initiate translation in a cap-independent manner. It is often related to cellular processes and many diseases. Thus, identifying the IRES is important for understanding its mechanism and finding potential therapeutic strategies for relevant diseases since identifying IRES elements by experimental method is time-consuming and laborious. Many bioinformatics tools have been developed to predict IRES, but all these tools are based on structure similarity or machine learning algorithms. Here, we introduced a deep learning model named DeepIRES for precisely identifying IRES elements in messenger RNA (mRNA) sequences. DeepIRES is a hybrid model incorporating dilated 1D convolutional neural network blocks, bidirectional gated recurrent units, and self-attention module. Tenfold cross-validation results suggest that DeepIRES can capture deeper relationships between sequence features and prediction results than other baseline models. Further comparison on independent test sets illustrates that DeepIRES has superior and robust prediction capability than other existing methods. Moreover, DeepIRES achieves high accuracy in predicting experimental validated IRESs that are collected in recent studies. With the application of a deep learning interpretable analysis, we discover some potential consensus motifs that are related to IRES activities. In summary, DeepIRES is a reliable tool for IRES prediction and gives insights into the mechanism of IRES elements.
An unusual case of dorsal hand papules and nodules
Authors: MacKinnon Lauren , Wijesuriya Nilukshi , Tiffin Nick , Ntala Chara , Jiyad Zainab , Samarasinghe Ven
Published: September 2024

A 56-year-old woman presented with a 4-year history of slow-growing asymptomatic nodules over the dorsal aspects of the hands. Subtle histological features lead to the diagnosis of an uncommon condition.
Outcome after left ventricular assist device exchange
Authors: Niamat Jaiel , Ramjankhan Faiz , Van Der Kaaij Niels , Gianoli Monica , Van Laake Linda W , Mokhles Mostafa M
Published: September 2024

OBJECTIVES

Left ventricular assist device (LVAD) therapy has evolved from a short-term bridge-to-transplant strategy into a long-term and often chronic therapy due to long waiting times for heart transplantation and application as destination therapy. Consequently, patients are at risk of developing complications necessitating LVAD exchange. The aim of this study is to assess patient outcomes after LVAD exchange.

METHODS

Patients who underwent LVAD exchange between January 2010 and December 2022 were included. Logistic and cox regression analyses were used to identify potential risk factors for short and long-term adverse events, respectively. Survival after exchange was assessed using Kaplan–Meier estimates.

RESULTS

Sixty-one patients underwent a total of 80 LVAD exchanges. Most frequently observed short-term complications were pulmonary infections (16.3%) and right heart failure (16.3%). Exit-site infections (34.7%) and device malfunctions (25.3%) were the most often observed long-term complications. HeartWare ventricular assist device as index device was associated with a higher risk of right heart failure [hazard ratio 6.42, 95% confidence interval (CI) 1.80–22.90] and respiratory failure (hazard ratio 7.81, 95% CI 1.95–31.23) compared to HeartMate II and HeartMate 3. Survival was 83% (95% CI 75.5–95.3%) at 1 year and 67% (95% CI 53.9–84.7%) at 6 years after exchange. After 5 years, 25.0% was transplanted, 23.8% had undergone a re-exchange and 32.5% was alive without new intervention.

CONCLUSIONS

Although LVAD exchange can be performed with a relatively low mortality, other post-operative adverse events are common. Patients with the HeartWare ventricular assist device as index device may be at higher risk of developing right heart failure and respiratory failure after exchange.
Refugee Memoirs: Kouamé’s Revenu des ténèbres (2018) and Dina Nayeri’s The Ungrateful Refugee (2019) and the Challenge of Refugee Narratives
Authors: Kistnareddy Ashwiny O
Published: September 2024

In their introduction to Values of Literature, Hanna Meretoja and Pyro Lyytikäinen argue that ‘little attention has been paid to the ethical relevance of different literary genres and to the very different functions of literary texts that make literature valuable’.1 Literature has several ‘uses’ according to Rita Felski (2008), amongst which are the ‘knowledge’ and ‘shock’ elements insofar as they enable readers to change their perception of the world. Examining what I term ‘refugee memoirs’ as an emergent genre and its uses in enabling readers to interrogate dominant discourses about refugees in the UK, Europe and North America, I argue that refugee memoirs contest right-wing narratives that seek to shape society’s view of asylum-seekers and refugees and enable readers to see refugees' lived experiences through new perspective. Thereby, these narratives also permit a rehumanization of refugees and a comprehension of their losses and positions.
New Insights into the Diversity of Mitochondrial Plastid DNA
Authors: Nhat Nam Nguyen , Pham Anh Thi Nguyen , Do Hoang Dang Khoa
Published: September 2024

The mitochondrial plastid DNAs (MTPTs) in seed plants were reported more than 40 years ago and exhibited a high diversity regarding gene content, quantity, and size. However, the mechanism that resulted in the current diversity of MTPTs in angiosperms has not been fully discovered. In this study, we sequenced and characterized the complete organelle genomes of Limonia acidissima L., a monotypic species of Rutaceae. The newly generated and previously published organelle genomes of 42 species were used to explore the diversity of MTPTs regarding quantity, gene content, size, and coverage of chloroplast genome (cpDNA) regions. The results showed that the number of MTPTs ranged from three to 74, of which the lengths were from 100 to 53,731 bp. The highest coverage of MTPTs was found in the inverted repeat region, whereas the small single repeat region had the lowest coverage. Based on the previous data and current results, we propose a scenario for the diversity of MTPTs in angiosperms. In the first stage, the whole cpDNA might migrate to the mitogenome. Then, different genomic events, such as duplication, deletion, substitution, and inversion, have occurred continuously and independently and resulted in extremely variable profiles of mitogenomes among angiosperms. Our hypothesis provides a new and possibly reliable scenario for explaining the present circumstances of MTPTs in angiosperms. However, more genomic data should be mined, and more studies should be conducted to clarify this natural phenomenon in plants.
The Genomic and Cultural Diversity of the Inka Qhapaq Hucha Ceremony in Chile and Argentina
Authors: de la Fuente Castro Constanza , Cortés Constanza , Raghavan Maanasa , Castillo Daniela , Castro Mario , Verdugo Ricardo A , Moraga Mauricio
Published: September 2024

The South American archaeological record has ample evidence of the socio-cultural dynamism of human populations in the past. This has also been supported through the analysis of ancient genomes, by showing evidence of gene flow across the region. While the extent of these signals is yet to be tested, the growing number of ancient genomes allows for more fine-scaled hypotheses to be evaluated. In this study, we assessed the genetic diversity of individuals associated with the Inka ritual, Qhapaq hucha. As part of this ceremony, one or more individuals were buried with Inka and local-style offerings on mountain summits along the Andes, leaving a very distinctive record. Using paleogenomic tools, we analyzed three individuals: two newly generated genomes from El Plomo Mountain (Chile) and El Toro Mountain (Argentina), and a previously published genome from Argentina (Aconcagua Mountain). Our results reveal a complex demographic scenario with each of the individuals showing different genetic affinities. Furthermore, while two individuals showed genetic similarities with present-day and ancient populations from the southern region of the Inka empire, the third individual may have undertaken long-distance movement. The genetic diversity we observed between individuals from similar cultural contexts supports the highly diverse strategies Inka implemented while incorporating new territories. More broadly, this research contributes to our growing understanding of the population dynamics in the Andes by discussing the implications and temporality of population movements in the region.
One-carbon metabolites supplementation and nutrient restriction alter the fetal liver metabolomic profile during early gestation in beef heifers
Authors: Safain Kazi Sarjana , Crouse Matthew S , Syring Jessica G , Entzie Yssi L , King Layla E , Hirchert Mara R , Ward Alison K , Reynolds Lawrence P , Borowicz Pawel P , Dahlen Carl R , Swanson Kendall C , Caton Joel S
Published: September 2024

Maternal nutrition is pivotal for proper fetal development, with one-carbon metabolites (OCM) playing a key role in fetal epigenetic programming through DNA and histone methylation. The study aimed to investigate the effects of nutrient restriction and OCM supplementation on fetal liver metabolomics in pregnant beef-heifers, focusing on metabolites and pathways associated with amino acid, vitamin and cofactor, carbohydrate, and energy metabolism at day 63 of gestation. Thirty-one crossbred Angus heifers were artificially inseminated and allocated to 4 nutritional treatments in a 2 × 2 factorial arrangement of treatments, with the 2 factors being dietary intake/rate of gain (control-diet [CON]; 0.60 kg/d ADG, vs. restricted-diet [RES]; −0.23 kg/d ADG) and OCM supplementation (supplemented [+OCM] vs. not supplemented [−OCM]). The resulting treatment groups—CON − OCM, CON + OCM, RES − OCM, and RES + OCM were maintained for 63 day post-breeding. Following this period, fetal liver tissues were collected and subjected to metabolomic analysis using UPLC-tandem mass-spectrometry. We identified 288 metabolites, with the majority (n = 54) being significantly influenced by the main effect of gain (P ≤ 0.05). Moreover, RES showed decreased abundances of most metabolites in pathways such as lysine metabolism; leucine, isoleucine, and valine metabolism; and tryptophan metabolism, compared to CON. Supplementation with OCM vs. no OCM supplementation, resulted in greater abundance of metabolites (P ≤ 0.05) affecting pathways associated with methionine, cysteine, S-adenosylmethionine and taurine metabolism; guanidino and acetamido metabolism; and nicotinate and nicotinamide metabolism. Notably, OCM supplementation with a moderate rate of gain increased the concentrations of ophthalmate, N-acetylglucosamine, and ascorbic-acid 3-sulfate, which are important for proper fetal development (P ≤ 0.05). Nutrient restriction reduced the majority of liver metabolites, while OCM supplementation increased a smaller number of metabolites. Thus, OCM supplementation may be protective of metabolite concentrations in key developmental pathways, which could potentially enhance fetal development under nutrient-restricted conditions.
A chromosome-level genome assembly of the common eider, Somateria mollissima (Linnaeus, 1758)
Authors: Tørresen Ole K , Kersten Oliver , Garmann-Aarhus Benedicte , Helberg Morten , Tooming-Klunderud Ave , Skage Morten , Boessenkool Sanne , Jakobsen Kjetill S
Published: September 2024

The common eider, Somateria mollissima mollissima (Chordata; Aves; Anseriformes; Anatidae), is a large sea duck with a circumpolar distribution. We here describe a chromosome-level genome assembly from an individual female. The haplotype-resolved assembly contains one pseudo-haplotype spanning 1,205 megabases (with both Z and W sex chromosomes) and one pseudo-haplotype spanning 1,080 megabases. Most of these two assemblies (91.13% and 93.18%, respectively) are scaffolded into 32 autosomal chromosomal pseudomolecules plus Z and W for pseudo-haplotype one. The BUSCO completeness scores are 94.0% and 89.9%, respectively, and gene annotations of the assemblies identified 17,479 and 16,315 protein coding genes. Annotation of repetitive sequences classify 17.84% and 14.62% of pseudo-haplotype one and two, respectively, as repeats. The genome of the common eider will be a useful resource for the widely distributed northern species in light of climate change and anthropogenic threats.
The Interpretation of Relative and Absolute Adjectives Under Negation
Authors: Alexandropoulou Stavroula , Gotzner Nicole
Published: September 2024

Negation typically has a contradictory effect on interpretation. At the same time, negated statements are often underinformative, which leaves room for pragmatic effects such as negative strengthening, where negated adjectives are pragmatically strengthened to convey their antonym (e.g., not large  $\leadsto $ ‘small’). Here, we investigate a theoretical controversy relating to the mechanism deriving negative strengthening effects. According to Horn's (1989) account negative strengthening arises on the basis of social considerations, whereas on Krifka's (2007) account it arises via complexity-based considerations, yielding distinct interpretation patterns. We applied Horn's (1989) and Krifka's (2007) accounts to three distinct cases of negated antonymic adjectives: informationally weak relative adjectives, informationally weak absolute adjectives, and informationally strong gradable adjectives. Our experimental results demonstrate different interpretation patterns for weak relative (large/small) and weak absolute gradable adjectives (clean/dirty) under negation. These results confirm the predictions stemming from Horn's (1989) account of negative strengthening effects and highlight the importance of a semantic extension gap between antonymic predicates for the occurrence of negative strengthening. In contrast, our experimental findings concerning strong antonymic adjectives (e.g., not gigantic/not tiny) prima facie present challenges for Horn's (1989) analysis, while they do not endorse any alternative account.
Relationship between self-efficacy, coping, and sense of community in native and refugee adolescent girls
Authors: Öner Mücahide , Emiroğlu Oya-Nuran
Published: September 2024

Understanding the self-efficacy, coping styles, and sense of community of native and refugee adolescent girls, who receive the same education, is essential for developing a more comprehensive understanding of adolescent development. This study compares the self-efficacy, coping, and sense of community of native and refugee adolescent girl students. This cross-sectional and correlational study was conducted with 384 native and refugee adolescent girl students in Turkey with an average of 16.05 years (SD = 1.34). Refugee adolescent girls were found to have higher levels of academic self-efficacy and sense of community than native adolescent girls. As the number of adolescents’ friends increased, their self-efficacy levels also increased. Native and refugee adolescent girls have similar needs, so effective and appropriate school-based programs with a more family-oriented approach that focuses on mothers should be implemented to develop adolescents’ self-efficacy, coping skills, and sense of community.
Surgical treatment of traumatic rupture of the teres major tendon in a professional gymnast: a case report
Authors: Berto Leonardo , Paroneto Arthur Cardoso , Vasconcelos Gabriel Ferreira Santos , Lima Ewerton Borges de Souza , Lara Paulo Henrique Schmidt , Belangero Paulo Santoro , Andreoli Carlos Vicente , Pochini Alberto de Castro , Ejnisman Benno
Published: September 2024

Teres major injuries are rare and are generally treated conservatively, except in high-performance athletes. This report describes a case of traumatic rupture of the teres major at its myotendinous junction in a professional gymnast. The patient underwent surgical treatment 10 days after the injury. Six months post-surgery, the patient achieved complete recovery of the range of motion and strength, returning to the pre-injury performance level, guided by physiotherapy rehabilitation. This is the first documented case in the literature of surgical treatment of this injury in a professional gymnast. The main lesson from this case is that early surgical repair in elite athletes can result in excellent functional outcomes and allow return to sport at the pre-injury performance level.
General Provisions
Authors: Wilman Folkert , Kalėda Saulius Lukas , Loewenthal Paul-John
Published: September 2024

This chapter focuses on the general provisions constituting the highest layer of the Digital Services Act (DSA). It explains that the provisions primarily serve as a basis for teleological interpretation of its provisions. Moreover, the provisions of Article 1 highlighted the objectives and subjective matters of the DSA. The chapter then discusses the DSA's objective of contributing to the proper functioning of the internal market and ensuring a safe, predictable, and trusted online environment. It then details the provisions as per Articles 2 and 3 of the DSA, both of which are also vital to delimiting the DSA’s scope of application in general and in relation to other EU acts.
Due Diligence Obligations for a Transparent and Safe Online Environment
Authors: Wilman Folkert , Kalėda Saulius Lukas , Loewenthal Paul-John
Published: September 2024

This chapter provides an overview of the due diligence obligations for a transparent and safe online environment. It notes the complexity of the position of online search engines. The lowest tier of due diligence obligations imposed on the broadest category of intermediary service providers applies regardless of the intermediary service and the size of the provider. The chapter then discusses the significance of online platforms in the dissemination of information as the societal risks related to their activity differ in nature and scale. It explains the self-regulation of digital services, so standards, codes of conduct, and crisis protocols primarily aim to achieve coordination and ensure a safe online environment.
A Novel Expression Domain of extradenticle Underlies the Evolutionary Developmental Origin of the Chelicerate Patella
Authors: Klementz Benjamin C , Brenneis Georg , Hinne Isaac A , Laumer Ethan M , Neu Sophie M , Hareid Grace M , Gainett Guilherme , Setton Emily V W , Simian Catalina , Vrech David E , Joyce Isabella , Barnett Austen A , Patel Nipam H , Harvey Mark S , Peretti Alfredo V , Gulia-Nuss Monika , Sharma Prashant P
Published: September 2024

Neofunctionalization of duplicated gene copies is thought to be an important process underlying the origin of evolutionary novelty and provides an elegant mechanism for the origin of new phenotypic traits. One putative case where a new gene copy has been linked to a novel morphological trait is the origin of the arachnid patella, a taxonomically restricted leg segment. In spiders, the origin of this segment has been linked to the origin of the paralog dachshund-2, suggesting that a new gene facilitated the expression of a new trait. However, various arachnid groups that possess patellae do not have a copy of dachshund-2, disfavoring the direct link between gene origin and trait origin. We investigated the developmental genetic basis for patellar patterning in the harvestman Phalangium opilio, which lacks dachshund-2. Here, we show that the harvestman patella is established by a novel expression domain of the transcription factor extradenticle. Leveraging this definition of patellar identity, we surveyed targeted groups across chelicerate phylogeny to assess when this trait evolved. We show that a patellar homolog is present in Pycnogonida (sea spiders) and various arachnid orders, suggesting a single origin of the patella in the ancestor of Chelicerata. A potential loss of the patella is observed in Ixodida. Our results suggest that the modification of an ancient gene, rather than the neofunctionalization of a new gene copy, underlies the origin of the patella. Broadly, this work underscores the value of comparative data and broad taxonomic sampling when testing hypotheses in evolutionary developmental biology.
Engineered Cas9 variants bypass Keap1-mediated degradation in human cells and enhance epigenome editing efficiency
Authors: Chen Jianfeng , Su Siyuan , Pickar-Oliver Adrian , Chiarella Anna M , Hahn Quentin , Goldfarb Dennis , Cloer Erica W , Small George W , Sivashankar Smaran , Ramsden Dale A , Major Michael B , Hathaway Nathaniel A , Gersbach Charles A , Liu Pengda
Published: September 2024

As a potent and convenient genome-editing tool, Cas9 has been widely used in biomedical research and evaluated in treating human diseases. Numerous engineered variants of Cas9, dCas9 and other related prokaryotic endonucleases have been identified. However, as these bacterial enzymes are not naturally present in mammalian cells, whether and how bacterial Cas9 proteins are recognized and regulated by mammalian hosts remain poorly understood. Here, we identify Keap1 as a mammalian endogenous E3 ligase that targets Cas9/dCas9/Fanzor for ubiquitination and degradation in an ‘ETGE’-like degron-dependent manner. Cas9-‘ETGE’-like degron mutants evading Keap1 recognition display enhanced gene editing ability in cells. dCas9-‘ETGE’-like degron mutants exert extended protein half-life and protein retention on chromatin, leading to improved CRISPRa and CRISPRi efficacy. Moreover, Cas9 binding to Keap1 also impairs Keap1 function by competing with Keap1 substrates or binding partners for Keap1 binding, while engineered Cas9 mutants show less perturbation of Keap1 biology. Thus, our study reveals a mammalian specific Cas9 regulation and provides new Cas9 designs not only with enhanced gene regulatory capacity but also with minimal effects on disrupting endogenous Keap1 signaling.
A global overview of health system financing and available infrastructure and oversight for kidney care
Authors: Yeung Emily K , Khanal Rohan , Sarki Abdulshahid , Arruebo Silvia , Damster Sandrine , Donner Jo-Ann , Caskey Fergus J , Jha Vivekanand , Levin Adeera , Nangaku Masaomi , Saad Syed , Ye Feng , Okpechi Ikechi G , Bello Aminu K , Tonelli Marcello , Johnson David W
Published: September 2024

Background

Governance, health financing, and service delivery are critical elements of health systems for provision of robust and sustainable chronic disease care. We leveraged the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to evaluate oversight and financing for kidney care worldwide.

Methods

A survey was administered to stakeholders from countries affiliated with the ISN from July to September 2022. We evaluated funding models utilized for reimbursement of medications, services for the management of chronic kidney disease, and provision of kidney replacement therapy (KRT). We also assessed oversight structures for the delivery of kidney care.

Results

Overall, 167 of the 192 countries and territories contacted responded to the survey, representing 97.4% of the global population. High-income countries tended to use public funding to reimburse all categories of kidney care in comparison with low-income countries (LICs) and lower-middle income countries (LMICs). In countries where public funding for KRT was available, 78% provided universal health coverage. The proportion of countries that used public funding to fully reimburse care varied for non-dialysis chronic kidney disease (27%), dialysis for acute kidney injury (either hemodialysis or peritoneal dialysis) (44%), chronic hemodialysis (45%), chronic peritoneal dialysis (42%), and kidney transplant medications (36%). Oversight for kidney care was provided at a national level in 63% of countries, and at a state/provincial level in 28% of countries.

Conclusion

This study demonstrated significant gaps in universal care coverage, and in oversight and financing structures for kidney care, particularly in in LICs and LMICs.
Global access and quality of conservative kidney management
Authors: Hole Barnaby , Wearne Nicola , Arruebo Silvia , Caskey Fergus J , Damster Sandrine , Donner Jo-Ann , Jha Vivekanand , Levin Adeera , Nangaku Masaomi , Saad Syed , Tonelli Marcello , Ye Feng , Okpechi Ikechi G , Bello Aminu K , Johnson David W , Davison Sara N
Published: September 2024

Background

Conservative kidney management (CKM) describes supportive care for people living with kidney failure who choose not to receive or are unable to access kidney replacement therapy (KRT). This study captured the global availability of CKM services and funding.

Methods

Data came from the International Society of Nephrology Global Kidney Health survey conducted between June and September 2022. Availability of CKM, infrastructure, guidelines, medications and training were evaluated.

Results

CKM was available in some form in 61% of the 165 responding countries. CKM chosen through shared decision-making was available in 53%. Choice-restricted CKM—for those unable to access KRT—was available in 39%. Infrastructure to provide CKM chosen through shared decision-making was associated with national income level, reported as being “generally available” in most healthcare settings for 71% of high-income countries, 50% of upper-middle-income countries, 33% of lower-middle-income countries and 42% of low-income countries. For choice-restricted CKM, these figures were 29%, 50%, 67% and 58%, respectively. Essential medications for pain and palliative care were available in just over half of the countries, highly dependent upon income setting. Training for caregivers in symptom management in CKM was available in approximately a third of countries.

Conclusions

Most countries report some capacity for CKM. However, there is considerable variability in terms of how CKM is defined, as well as what and how much care is provided. Poor access to CKM perpetuates unmet palliative care needs, and must be addressed, particularly in low-resource settings where death from untreated kidney failure is common.
Ideologies of Political Constitutionalism
Authors: Greally Robert
Published: September 2024

For many political constitutionalists, the ordinary democratic process should be the constitution; constitutional entrenchment and strong-form judicial review should be avoided. But how is ordinary democratic politics understood by political constitutionalists? To answer this question, this article engages in an interpretative inquiry to delineate four distinct ideological readings of political constitutionalism—democratic socialist, liberal, republican and conservative—that are alive within the existing literature. It does so to explain how these readings articulate subtly different understandings of ordinary democratic politics. In doing so, it reflects on how to identify political constitutionalist thought; how political constitutionalism can appeal to different ideologies; how ideologies have influenced the theory’s intellectual development; and the ideological conditions required to sustain a political constitution.
Radiotherapy with targeted and immunotherapy improved overall survival and progression-free survival for hepatocellular carcinoma with portal vein tumor thrombosis
Authors: Ma Jianing , Zhang Haifeng , Zheng Ruipeng , Wang Shudong , Ding Lijuan
Published: September 2024

Background

The efficacy of radiotherapy (RT) combined with targeted therapy and immunotherapy in treating hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is still unclear. This study investigated the efficacy and safety of RT combined with targeted therapy and immunotherapy in HCC with PVTT.

Materials and Methods

Seventy-two patients with HCC with PVTT treated with tyrosine kinase inhibitor (TKI) plus programmed cell death protein-1 (PD-1) inhibitor with or without RT from December 2019 to December 2023 were included. After propensity score matching (PSM) for adjusting baseline differences, 32 pairs were identified in RT + TKI + PD-1 group (n = 32) and TKI + PD-1 group (n = 32). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs).

Results

Median OS (mOS) in RT + TKI + PD-1 group was significantly longer than TKI + PD-1 group (15.6 vs. 8.2 months, P = .008). Median PFS (mPFS) in RT + TKI + PD-1 group was dramatically longer than TKI + PD-1 group (8.1 vs. 5.2 months, P = .011). Patients in TKI + PD-1 + RT group showed favorable ORR and DCR compared with TKI + PD-1 group (78.1% vs. 56.3%, P = .055; 93.8% vs. 81.3%, P = .128). Subgroup analysis demonstrated a remarkable OS and PFS benefit with TKI + PD-1 + RT for patients with main PVTT (type III/IV) and those of Child-Pugh class A. Multivariate analysis confirmed RT + TKI + PD-1 as an independent prognostic factor for longer OS (HR 0.391, P = .024) and longer PFS (HR 0.487, P = .013), with no mortality or severe TRAEs.

Conclusion

RT combined with TKI and PD-1 inhibitor could significantly improve mOS and mPFS without inducing severe TRAEs or mortality.
A Comprehensive 2022 Look at the Empirical Performance of Equity Premium Prediction
Authors: Goyal Amit , Welch Ivo , Zafirov Athanasse
Published: September 2024

Our paper reexamines whether 29 variables from 26 papers published after Goyal and Welch 2008, as well as the original 17 variables, were useful in predicting the equity premium in-sample and out-of-sample as of the end of 2021. Our samples include the original periods in which these variables were identified, but end later. More than one-third of these new variables no longer have empirical significance even in-sample. Of those that do, half have poor out-of-sample performance. A small number of variables still perform reasonably well both in-sample and out-of-sample.
Intravenous fosfomycin indications and treatment outcomes in pediatric usage: analysis from a single center in Turkey
Authors: Kanık-Yüksek Saliha , Güneş Ömer , Gülhan Belgin , Erat Tuğba , Konca Hatice Kübra , Özen Seval , Yahşi Aysun , Bayhan Gülsüm İclal , Özkaya-Parlakay Aslınur
Published: September 2024

Current data on fosfomycin usage in children are limited. We present data on the clinical use of intravenous (IV) fosfomycin in children. Hospitalized patients who received ≥3 days of IV fosfomycin between April 2021 and March 2023 were analyzed retrospectively. Forty-three episodes of infection in 39 patients were evaluated. The mean age of the patients was 5.35 (10 days to 17.5 years) years, and 54% were male. Infections were hospital-acquired in 79% of the episodes. Indications for fosfomycin were urinary tract infection (35%), bacteremia (32.6%), catheter-related bloodstream infection (16.3%), soft tissue infection (4.7%), sepsis (4.7%), surgical site infection (2.3%), burn infection (2.3%), and pneumonia (2.3%). Klebsiella pneumoniae was identified in 46.5% of the episodes, and a pan-drug or extensive drug resistance was detected in 75% of them. Carbapenem was used before fosfomycin at significantly higher rates in K. pneumoniae episodes (P = .006). Most (88.5%) patients received fosfomycin as a combination therapy. Culture negativity was achieved in 80% of episodes within a median treatment period of 3 (2–22) days, which was significantly shorter in K. pneumoniae episodes (P < .001). Treatment-related side effects were seen in 9.3% of the episodes. Side effects were significant after 3 weeks of treatment (P = .013). The unresponsivity rate to fosfomycin was 23.3%. Nine (21%) of the patients who were followed up in the intensive care units mainly died because of sepsis (56%). IV fosfomycin is an effective agent in treating severe pediatric infections caused by resistant microorganisms. Fosfomycin can be used in various indications and is generally safe for children.
Foetal outcome of Leptospira and Rickettsial infections during pregnancy: a systematic review
Authors: Sengupta Mallika , T Latha , Mandal Soumitra , Mukhopadhyay Kaushik
Published: September 2024

Background

Leptospirosis and rickettsial infections are bacterial zoonoses prevalent in different geographical locations and presents with overlapping symptoms.

Objective

To identify foetal outcomes in pregnant women diagnosed with rickettsial infections, including scrub typhus and leptospirosis, along with their associated factors.

Methods

A comprehensive search was conducted in MEDLINE/PubMed, Scopus, CENTRAL (Cochrane), Web of Science, PsycINFO, Academic Search Premier, CINAHL, and Embase using defined search terms. Studies involving pregnant women with diagnosed leptospirosis and rickettsial infections, including scrub typhus, were selected. Two independent reviewers screened titles and abstracts using the Rayyan Web interface. Data extraction was performed in Microsoft Excel, with Zotero for reference management. Study quality was assessed using Joanna Briggs Institute Critical Appraisal tools. Data synthesis included narrative analysis.

Results

Fifty-four studies were included: 22 on scrub typhus, 14 on rickettsial infection, 16 on leptospirosis, and 2 on all three infections. Of 176 scrub typhus cases, 53 resulted in foetal loss and 3 in neonatal death. Among 38 rickettsial infection cases, 4 had foetal loss. Out of 63 leptospirosis cases, 13 experienced foetal loss. Six maternal deaths occurred due to scrub typhus and one due to Rocky Mountain spotted fever.

Conclusion

Leptospirosis and rickettsial infections, including scrub typhus, are important causes of pregnancy loss. Further research is needed to better understand and mitigate these risks in pregnant women.
Diversity and Characteristics of Fusarium solani Species Complex (FSSC) Isolates Causing Collar Rot and Fruit Rot of Passion Fruit in Taiwan
Authors: Lo Pei-Hsin , Huang Jin-Hsing , Chang Chia-Chih , Namisy Ahmed , Chen Chi-Yu , Chung Wen-Hsin
Published: September 2024

Fusarium solani species complex (FSSC) is a causal agent of collar rot and fruit rot in passion fruit worldwide. This study investigated the diversity and characteristics of FSSC isolates causing collar rot and fruit rot in Taiwanese passion fruit. Thirty-five FSSC isolates were harvested from collar rot and fruit rot samples of passion fruit from various cultivars and different geographical locations in Taiwan. The majority of these FSSC isolates caused collar rot and fruit rot disease of varying virulence in the stems and fruits of the purple and yellow cultivars of passion fruit. FSSC isolates were categorized into four groups: F. solani-melongenae (FSSC 21; n = 29), F. solani (FSSC 5; n = 1), F. liriodendri (FSSC 24; n = 1), and an unknown group (n = 4) based on the phylogenetic analysis of internal transcribed sequence (ITS), translation elongation factor 1 alpha (TEF-1α), and RNA polymerase II subunit 2 (RPB2) sequences. In Taiwan, F. solani-melongenae was the dominant species causing collar rot and fruit rot in passion fruit. F. solani-melongenae was a homothallic fungus that produced perithecia in diseased tissues. However, F. solani and F. liriodendri did not produce perithecia. The unknown FSSC group showed morphological characteristics similar to F. solani-melongenae and produced perithecia. Phylogenetic analysis based on the ITS and TEF-1α sequences demonstrated that the Taiwanese FSSC isolates were distinct from the Brazilian and Chinese FSSC isolates. In summary, FSSC isolates causing collar rot and fruit rot of Taiwanese passion fruit showed high diversity, potentially associated with the geographical locations.
Different Risk Factors between Bony and Ligamentous Proximal Junctional Failure in Patients Undergoing Thoracolumbar Fusion to Pelvis for Adult Spinal Deformity
Authors: Park Se-Jun , Park Jin-Sung , Kang Dong-Ho , Kang Minwook , Jung Kyunghun , Lee Chong-Suh
Published: September 2024

Study Design.

Retrospective study

Objective.

To analyze the risk factors for bony proximal junctional failure (B-PJF) and ligamentous PJF (L-PJF) separately after adult spinal deformity (ASD) surgery

Summary of Background Data.

Despite numerous studies about the risk factors of PJF, it remains unclear whether same risk factors can be applied to both B-PJF and L-PJF.

Methods.

Patients who underwent corrective surgery from low thoracic level (T9-T12) to pelvis with minimum follow-up duration of two years were included in this study. Patients with PJF were divided into two groups according to the involvement of bony structure: B-PJF and L-PJF. The control group was created using patients who did not develop PJF for ≥2 years postoperatively (no-PJF group). Risk factors were analyzed by comparing various clinical and radiographic parameters between no PJF versus B-PJF group and between no PJF versus L-PJF groups.

Results.

The final study cohort comprised 240 patients. The mean age was 68.7 years, and there were 205 women (85.4%). On average, 8.1 levels were fused. PJF developed in 103 patients, with 70 (68.0%) in the B-PJF group and 33 (32.0%) in the L-PJF group. Stepwise logistic regression analyses revealed that older age (odds ratio [OR]=1.088), higher body mass index (BMI) (OR=1.161), osteoporosis (OR=3.293), greater postoperative lumbar distribution index (OR=1.032), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis (OR=3.964) were significant risk factors for B-PJF. Meanwhile, no use of transverse process (TP) hook was the single risk factor for L-PJF (OR=4.724).

Conclusions.

Understanding the difference in risk factors between B-PJF and L-PJF will facilitate the optimization of surgical outcome for patients with ASD. Appropriate correction of sagittal malalignment along with use of TP hook is advisable to mitigate both B-PJF and L-PJF development.
The Case of Dolutegravir Plus Darunavir Antiretroviral Regimens: Is It Always Useful to Double the Drug Doses? A Short Communication
Authors: Cattaneo Dario , Ridolfo Anna Lisa , Giacomelli Andrea , Castagna Antonella , Dolci Alberto , Antinori Spinello , Gervasoni Cristina
Published: September 2024

Background:

Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations.

Methods:

This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations.

Results:

A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05).

Conclusions:

Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug–drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH.
Successful rehabilitation after surgical repair of hip fracture has been associated with handgrip strength but not with orthostatic hypotension in patients 65 years of age and above
Authors: Hilali Abdu El Karim , Shacham David , Frenkel Reut , Abu-Ajaj Ahmed , Zikrin Evgeniya , Freud Tamar , Press Yan
Published: September 2024

Objective

The identification of factors associated with successful rehabilitation after hip fractures enables more successful planning of the rehabilitation process and discharge from the hospital. Orthostatic hypotension (OH) and handgrip strength (HGS) have been evaluated in previous studies as potential predictors of rehabilitation outcomes, with inconsistent results.

Design

A retrospective study of patients 65 years of age and above who underwent rehabilitation after surgical repair of hip fracture in the Geriatric Department between July 2020 and October 2023. HGS was measured during the first three days of hospitalization using a digital dynamometer. OH was measured a week after admission to the ward by the tilt table test. Successful rehabilitation was defined as a Montebello Rehabilitation Factor Score Revised (MRFS-R) above 50%.

Results

Data were collected for 253 patients. The mean age was 80.5 ± 7.7 and 32.4% were males. The mean HGS was 17.2 ± 6.6 kg. OH was diagnosed in 32.8%. 193 patients (76.3%) reached the goal of MRFS-R ≥ 50 at the end of the rehabilitation. In a logistic regression analysis HGS, cognitive state, and sex were associated with successful rehabilitation.

Conclusions

Measuring HGS, but not OH, can predict successful rehabilitation.