bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of land-use changes and management intensification on bacterial communities in the last decade: a review
Authors: Tomazelli Daniela , Klauberg-Filho Osmar , Mendes Lucas William , Goss-Souza Dennis
Published: June 2024

In the last decade, advances in soil bacterial ecology have contributed to increasing agricultural production. Brazil is the world leading agriculture producer and leading soil biodiversity reservoir. Meanwhile, there is still a significant gap in the knowledge regarding the soil microscopic life and its interactions with agricultural practices, and the replacement of natural vegetation by agroecosystems is yet to be unfolded. Through high throughput DNA sequencing, scientists are now exploring the complexity of soil bacterial communities and their relationship with soil and environmental characteristics. This study aimed to investigate the progress of bacterial ecology studies in Brazil over the last 10 years, seeking to understand the effect of the conversion of natural vegetation in agricultural systems on the diversity and structure of the soil microbial communities. We conducted a systematic search for scientific publication databases. Our systematic search has matched 62 scientific articles from three different databases. Most of the studies were placed in southeastern and northern Brazil, with no records of studies about microbial ecology in 17 out of 27 Brazilian states. Out of the 26 studies that examined the effects of replacing natural vegetation with agroecosystems, most authors concluded that changes in soil pH and vegetation cover replacement were the primary drivers of shifts in microbial communities. Understanding the ecology of the bacteria inhabiting Brazilian soils in agroecosystems is paramount for developing more efficient soil management strategies and cleaner agricultural technologies.
Trimerized S expressed by modified vaccinia virus Ankara (MVA) confers superior protection against lethal SARS-CoV-2 challenge in mice
Authors: Zhu Junda , Wang Zhenshan , Li Yarui , Zhang Zihui , Ren Shuning , Wang Jing , Xie Shijie , Liao Zhiyi , Song Baifen , Wu Wenxue , Yan Feihu , Peng Chen
Published: June 2024

The reoccurrence of successive waves of SARS-CoV-2 variants suggests the exploration of more vaccine alternatives is imperative. Modified vaccinia virus Ankara (MVA) is a virus vector exhibiting excellent safety as well as efficacy for vaccine development. Here, a series of recombinant MVAs (rMVAs) expressing monomerized or trimerized S proteins from different SARS-CoV-2 variants are engineered. Trimerized S expressed from rMVAs is found predominantly as trimers on the surface of infected cells. Remarkably, immunization of mice with rMVAs demonstrates that S expressed in trimer elicits higher levels of binding IgG and IgA, as well as neutralizing antibodies for matched and mismatched S proteins than S in the monomer. In addition, trimerized S expressed by rMVA induces enhanced cytotoxic T-cell responses than S in the monomer. Importantly, the rMVA vaccines expressing trimerized S exhibit superior protection against a lethal SARS-CoV-2 challenge as the immunized animals all survive without displaying any pathological conditions. This study suggests that opting for trimerized S may represent a more effective approach and highlights that the MVA platform serves as an ideal foundation to continuously advance SARS-CoV-2 vaccine development.

IMPORTANCE

MVA is a promising vaccine vector and has been approved as a vaccine for smallpox and mpox. Our analyses suggested that recombinant MVA expressing S in trimer (rMVA-ST) elicited robust cellular and humoral immunity and was more effective than MVA-S-monomer. Importantly, the rMVA-ST vaccine was able to stimulate decent cross-reactive neutralization against pseudoviruses packaged using S from different sublineages, including Wuhan, Delta, and Omicron. Remarkably, mice immunized with rMVA-ST were completely protected from a lethal challenge of SARS-CoV-2 without displaying any pathological conditions. Our results demonstrated that an MVA vectored vaccine expressing trimerized S is a promising vaccine candidate for SARS-CoV-2 and the strategy might be adapted for future vaccine development for coronaviruses.
Bile acids regulation of cellular stress responses in liver physiology and diseases
Authors: Li Tiangang , Hasan Mohammad Nazmul , Gu Lijie
Published: June 2024

Bile acids are physiological detergents and signalling molecules that are critically implicated in liver health and diseases. Dysregulation of bile acid homeostasis alters cell function and causes cell injury in chronic liver diseases. Therapeutic agents targeting bile acid synthesis, transport and signalling hold great potential for treatment of chronic liver diseases. The broad cellular and physiological impacts of pharmacological manipulations of bile acid metabolism are still incompletely understood. Recent research has discovered new links of bile acid signalling to the regulation of autophagy and lysosome biology, redox homeostasis and endoplasmic reticulum stress. These are well-conserved mechanisms that allow cells to adapt to nutrient and organelle stresses and play critical roles in maintaining cellular integrity and promoting survival. However, dysregulation of these cellular pathways is often observed in chronic liver diseases, which exacerbates cellular dysfunction to contribute to disease pathogenesis. Therefore, identification of these novel links has significantly advanced our knowledge of bile acid biology and physiology, which is needed to understand the contributions of bile acid dysregulation in disease pathogenesis, establish bile acids as diagnostic markers and develop bile acid-based pharmacological interventions. In this review, we will first discuss the roles of bile acid dysregulation in the pathogenesis of chronic liver diseases, and then discuss the recent findings on the crosstalk of bile acid signalling and cellular stress responses. Future investigations are needed to better define the roles of these crosstalks in regulating cellular function and disease processes.
A global redistributive auction for vaccine allocation
Authors: Sterri Aksel Braanen , Skjelbred Peder
Published: June 2024

The global allocation of vaccines during the COVID-19 pandemic is widely perceived as unfair. Priority was given to countries that paid the most with little or no concern for who needed the vaccines the most. No satisfactory institutions have been established to allocate vaccines in a future pandemic. In this paper, we join reformers in proposing a new scheme for vaccine distribution: a global auction for vaccines where profits are distributed fairly to participating countries. Our proposal improves upon previous suggestions morally by taking countries’ differing valuations of money and vaccines seriously. Since an auction is in the interest of both vaccine manufacturers and high-income countries, it is also politically feasible. A global redistributive auction for vaccines thus promises to be a robust and morally desirable way to allocate vaccines.
Intensity of statin therapy after ischaemic stroke and long-term outcomes: a nationwide cohort study
Authors: Kytö Ville , Åivo Julia , Ruuskanen Jori O
Published: June 2024

Background

Statins are essential for secondary prevention after ischaemic stroke (IS). However, statin intensity recommendations differ, and there is a concern about intracerebral haemorrhage (ICH). We studied the long-term impacts of initial statin intensity following IS.

Methods

Consecutive patients using high-intensity, moderate-intensity or low-intensity statin early after IS (n=45 512) were retrospectively studied using national registries in Finland. Differences were adjusted using multivariable regression. The primary outcome was all-cause death within 12-year follow-up (median 5.9 years). Secondary outcomes were recurrent IS, cardiovascular death and ICH studied using competing risk analyses.

Results

High-intensity therapy was initially used by 16.0%, moderate-intensity by 73.8% and low-intensity by 10.2%. Risk of death was lower with high-intensity versus moderate-intensity (adjusted HR (adj.HR) 0.92; 95% CI 0.87 to 0.97; number needed to treat (NNT) 32.0), with moderate-intensity versus low-intensity (adj.HR 0.91; 95% CI 0.87 to 0.95; NNT 27.5) and with high-intensity versus low-intensity (adj.HR 0.83; 95% CI 0.78 to 0.89; NNT 14.6) statin. There was a dose-dependent association of initial statin intensity with a lower probability of recurrent IS (p<0.0001) and cardiovascular death (p<0.0001). The occurrence of ICH was not associated with initial statin intensity (p=0.646).

Conclusions

Following IS, more intense initial statin treatment is associated with improved long-term outcomes but not with the risk of ICH. These findings emphasise the importance of high statin intensity shortly after IS.
Exploring causality with biliary atresia at different levels: two-sample Mendelian randomization study
Authors: Liu Shaowen , Musha Jiayinaxi , Wang Zhiru , Wang Xueting , Li Tengfei , Zhan Jianghua
Published: June 2024

Background

In recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to biliary atresia (BA).

Methods

Genome-wide association studies (GWAS) data of 41 inflammatory cytokines, 731 immune cell traits, and 1400 metabolites were obtained from public databases as exposure factors. The outcome information was obtained from a GWAS meta-analysis of 499 children with BA and 1928 normal controls. Inverse variance weighting was the primary causality analysis. Cochran Q-test, MR-Egger intercept, MR pleiotropy residual sum and outlier, and ‘leave-one-out’ analyses were used for sensitivity analysis. Reverse MR, MR-Steiger, and Linkage Disequilibrium Score were used to exclude the effects of reverse causality, genetic association, and linkage disequilibrium.

Results

MR results showed that a total of seven traits had potential causal relationships with BA, including three inflammatory cytokines: eotaxin (odds ratio (OR)=1.45, 95% confidence interval (CI): 1.08 to 1.95,pFDR=0.18), G-CSF (OR=4.21, 95% CI: 1.75 to 10.13,pFDR=0.05) and MCP-1/MCAF (OR=1.53, 95% CI: 1.12 to 2.10,pFDR=0.14); three immune cell traits: CD8dim NKT/T cells ratio (OR=0.59, 95% CI: 0.45 to 0.77,pFDR=0.06), CD8dim NKT counts (OR=0.58, 95% CI: 0.43 to 0.78,pFDR=0.06), CD8dim NKT/lymphocyte ratio (OR=0.63, 95% CI: 0.49 to 0.81,pFDR=0.06); one metabolite: X-12261 levels (OR=2.86, 95% CI: 1.73 to 4.74,pFDR=0.06).

Conclusions

In this study, eotaxin, G-CSF, MCP-1/MCAF, and X-12261 levels were shown to be risk factors for BA. However, CD8dim NKT/T cells ratio, CD8dim NKT counts, and CD8dim NKT/lymphocyte ratio were protective factors for BA. These findings provided a promising genetic basis for the etiology, diagnosis, and treatment of BA.
Seasonal changes in hydration in free-living Japanese children and adolescents
Authors: Amano Tatsuro , Sato Kotaro , Otsuka Junto , Okamoto Yumi , Takada Shota , Kato Hanano , Yokoyama Shotaro , Oshima Shoma , Hosokawa Yuri , Fujii Naoto , Mündel Toby , Kenny Glen P. , Hiwa Takako , Inoue Yoshimitsu
Published: June 2024

Changes in hydration status occur throughout the day affecting physiological and behavioural functions. However, little is known about the hydration status of free-living Japanese children and the seasonality of this response. We evaluated hydration status estimated by urine osmolality (Uosm) in 349 children (189 boys and 160 girls, 9.5 ± 2.6 years, range: 6–15 years) upon waking at home and during a single school day in spring (April) and summer (July). Further, we assessed the efficacy of employing self-assessment of urine colour (UC; based on an 8-point scale) by children to monitor their hydration status. Early morning Uosm was greater in the spring (903 ± 220 mOsm L−1; n = 326) as compared to summer (800 ± 244 mOsm L−1; n = 125) ( P = 0.003, paired t test, n = 104). No differences, however, were observed in Uosm during the school day ( P = 0.417, paired t test, n = 32). While 66% and 50% of children were considered underhydrated (Uosm ≥ 800 mOsm L−1) upon waking in the spring and summer periods, respectively, more children were underhydrated (∼12%) during the school day. Self-reported UC was similar between seasons as assessed in the morning and school day ( P ≥ 0.101, paired t test), which differed from the pattern of responses observed with Uosm. We showed that a significant number of Japanese children are likely underhydrated especially in the spring period. Children do not detect seasonal changes in hydration from self-assessed UC, limiting its utility to manage hydration status in children.
Automated Testing Linguistic Capabilities of NLP Models
Authors: Lee Jaeseong , Chen Simin , Mordahl Austin , Liu Cong , Yang Wei , Wei Shiyi
Published: June 2024

Natural language processing (NLP) has gained widespread adoption in the development of real-world applications. However, the black-box nature of neural networks in NLP applications poses a challenge when evaluating their performance, let alone ensuring it. Recent research has proposed testing techniques to enhance the trustworthiness of NLP-based applications. However, most existing works use a single, aggregated metric (i.e., accuracy) which is difficult for users to assess NLP model performance on fine-grained aspects, such as LCs. To address this limitation, we present ALiCT, an automated testing technique for validating NLP applications based on their LCs. ALiCT takes user-specified LCs as inputs and produces diverse test suite with test oracles for each of given LC. We evaluate ALiCT on two widely adopted NLP tasks, sentiment analysis and hate speech detection, in terms of diversity, effectiveness, and consistency. Using Self-BLEU and syntactic diversity metrics, our findings reveal that ALiCT generates test cases that are 190% and 2213% more diverse in semantics and syntax, respectively, compared to those produced by state-of-the-art techniques. In addition, ALiCT is capable of producing a larger number of NLP model failures in 22 out of 25 LCs over the two NLP applications.
Carefully Unmaking the “Marginalized User”: A Diffractive Analysis of a Gay Online Community
Authors: Taylor Jordan , Deng Wesley Hanwen , Holstein Kenneth , Fox Sarah , Zhu Haiyi
Published: June 2024

HCI scholars are increasingly engaging in research about “marginalized groups,” such as LGBTQ+ people. While normative habitual readings of marginalized people in HCI often highlight real problems, this work has been criticized for flattening heterogeneous experiences and overemphasizing harms. Some have advocated for expanding how we approach research on marginalized people (e.g., assets-based design, the everyday, and joy). Sensitized by unmaking literature, we explore this tension between conditions, experiences, and representations of marginality in HCI scholarship. To do so, we perform a diffractive analysis of posts in a gay online community by bringing two readings of the same data together: a normative habitual reading of marginalization and an expanded reading. By examining the relationship between empirical material and its representations by HCI researchers, we explore how to carefully unmake HCI research, thus maintaining and repairing our research community. We discuss the political and designerly implications of different readings of marginalized people and offer considerations for attending to the processes and afterlives of HCI research.
A Closer Look into IPFS: Accessibility, Content, and Performance
Authors: Shi Ruizhe , Cheng Ruizhi , Han Bo , Cheng Yue , Chen Songqing
Published: June 2024

The InterPlanetary File System (IPFS) has recently gained considerable attention. While prior research has focused on understanding its performance characterization and application support, it remains unclear: (1) what kind of files/content are stored in IPFS, (2) who are providing these files, (3) are these files always accessible, and (4) what affects the file access performance.

To answer these questions, in this paper, we perform measurement and analysis on over 4 million files associated with CIDs (content IDs) that appeared in publicly available IPFS datasets. Our results reveal the following key findings: (1) Mixed file accessibility: while IPFS is not designed for a permanent storage, accessing a non-trivial portion of files, such as those of NFTs and video streams, often requires multiple retrieval attempts, potentially blocking NFT transactions and negatively affecting the user experience. (2) Dominance of NFT (non-fungible token) and video files: about 50% of stored files are NFT-related, followed by a large portion of video files, among which about half are pirated movies and adult content. (3) Centralization of content providers: a small number of peers (top-50), mostly cloud nodes hosted by tech companies, serve a large portion (95%) of files, deviating from IPFS's intended design goal. (4) High variation of downloading throughput and lookup time: large file retrievals experience lower average throughput due to more overhead for resolving file chunk CIDs, and looking up files hosted by non-cloud nodes takes longer. We hope that our findings can offer valuable insights for (1) IPFS application developers to take into consideration these characteristics when building applications on top of IPFS, and (2) IPFS system developers to improve IPFS and similar systems to be developed for Web3.
Democratizing LEO Satellite Network Measurement
Authors: Izhikevich Liz , Tran Manda , Izhikevich Katherine , Akiwate Gautam , Durumeric Zakir
Published: June 2024

Low Earth Orbit (LEO) satellite networks are quickly gaining traction with promises of impressively low latency, high bandwidth, and global reach. However, the research community knows relatively little about their operation and performance in practice. The obscurity is largely due to the high barrier of entry for measuring LEO networks, which requires deploying specialized hardware or recruiting large numbers of satellite Internet customers. In this paper, we introduce HitchHiking, a methodology that democratizes global visibility into LEO satellite networks. HitchHiking builds on the observation that Internet-exposed services that use LEO Internet can reveal satellite network architecture and performance, bypassing the need for specialized hardware. We evaluate HitchHiking against ground truth measurements and prior methods, showing that it provides more coverage and accuracy. With HitchHiking, we complete the largest study to date of Starlink network latency, measuring over 2,400~users across 27~countries. We uncover unexpected patterns in latency that surface how LEO routing is more complex than previously understood. Finally, we conclude with recommendations for future research on LEO networks.
Invertible Bloom Lookup Tables with Listing Guarantees
Authors: Mizrahi Avi , Bar-Lev Daniella , Yaakobi Eitan , Rottenstreich Ori
Published: June 2024

The Invertible Bloom Lookup Table (IBLT) is a probabilistic concise data structure for set representation that supports a listing operation as the recovery of the elements in the represented set. Its applications can be found in network synchronization and traffic monitoring as well as in error-correction codes. IBLT can list its elements with probability affected by the size of the allocated memory and the size of the represented set, such that it can fail with small probability even for relatively small sets. While previous works only studied the failure probability of IBLT, this work initiates the worst case analysis of IBLT that guarantees successful listing for all sets of a certain size. The worst case study is important since the failure of IBLT imposes high overhead. We describe a novel approach that guarantees successful listing when the set satisfies a tunable upper bound on its size. To allow that, we develop multiple constructions that are based on various coding techniques such as stopping sets and the stopping redundancy of error-correcting codes, and Steiner systems as well as new methodologies we develop. We analyze the sizes of IBLTs with listing guarantees obtained by the various methods as well as their mapping memory and runtime overheads. Lastly, we study lower bounds on the achievable sizes of IBLT with listing guarantees and verify the results in the paper by simulations.
Multi-dimensional State Space Collapse in Non-complete Resource Pooling Scenarios
Authors: Cardinaels Ellen , Borst Sem , van Leeuwaarden Johan S.H.
Published: June 2024

We establish an explicit multi-dimensional state space collapse (SSC) for parallel-processing systems with arbitrary compatibility constraints between servers and job types. This breaks major new ground beyond the SSC results and queue length asymptotics in the literature which are largely restricted to complete resource pooling (CRP) scenarios where the steady-state queue length vector concentrates around a line in heavy traffic. The multi-dimensional SSC that we establish reveals heavy-traffic behavior which is also far more tractable than the pre-limit queue length distribution, yet exhibits a fundamentally more intricate structure than in the one-dimensional case.
Network Fairness Ambivalence: When Does Social Network Capital Mitigate or Amplify Unfairness?
Authors: Zhang Yiguang , Mukhopadhyay Reetahan , Chaintreau Augustin
Published: June 2024

What are the necessary and sufficient conditions under which multi-hop dissemination strategies decrease rather than increase inequity within social networks? Our analysis of various strategies suggests that this largely depends on a limit related to the degree of homophily in the network.
Online Conversion with Switching Costs: Robust and Learning-Augmented Algorithms
Authors: Lechowicz Adam , Christianson Nicolas , Sun Bo , Bashir Noman , Hajiesmaili Mohammad , Wierman Adam , Shenoy Prashant
Published: June 2024

We introduce and study online conversion with switching costs, a family of online problems that capture emerging problems at the intersection of energy and sustainability. In this problem, an online player attempts to purchase (alternatively, sell) fractional shares of an asset during a fixed time horizon with length T. At each time step, a cost function (alternatively, price function) is revealed, and the player must irrevocably decide an amount of asset to convert. The player also incurs a switching cost whenever their decision changes in consecutive time steps, i.e., when they increase or decrease their purchasing amount. We introduce competitive (robust) threshold-based algorithms for both the minimization and maximization variants of this problem, and show they are optimal among deterministic online algorithms. We then propose learning-augmented algorithms that take advantage of untrusted black-box advice (such as predictions from a machine learning model) to achieve significantly better average-case performance without sacrificing worst-case competitive guarantees. Finally, we empirically evaluate our proposed algorithms using a carbon-aware EV charging case study, showing that our algorithms substantially improve on baseline methods for this problem.
Shrinking VOD Traffic via Rényi-Entropic Optimal Transport
Authors: Lo Chi-Jen (Roger) , Marina Mahesh K. , Sastry Nishanth , Xu Kai , Fadaei Saeed , Li Yong
Published: June 2024

In response to the exponential surge in Video on Demand (VOD) traffic, numerous research endeavors have concentrated on optimizing and enhancing infrastructure efficiency. In contrast, this paper explores whether users' demand patterns can be shaped to reduce the pressure on infrastructure. Our main idea is to design a mechanism that alters the distribution of user requests to another distribution which is much more cache-efficient, but still remains 'close enough' (in terms of cost) to fulfil individual user's preference.
The Online Pause and Resume Problem: Optimal Algorithms and An Application to Carbon-Aware Load Shifting
Authors: Lechowicz Adam , Christianson Nicolas , Zuo Jinhang , Bashir Noman , Hajiesmaili Mohammad , Wierman Adam , Shenoy Prashant
Published: June 2024

We introduce and study the online pause and resume problem. In this problem, a player attempts to find the k lowest (alternatively, highest) prices in a sequence of fixed length T, which is revealed sequentially. At each time step, the player is presented with a price and decides whether to accept or reject it. The player incurs a switching cost whenever their decision changes in consecutive time steps, i.e., whenever they pause or resume purchasing. This online problem is motivated by the goal of carbon-aware load shifting, where a workload may be paused during periods of high carbon intensity and resumed during periods of low carbon intensity and incurs a cost when saving or restoring its state. It has strong connections to existing problems studied in the literature on online optimization, though it introduces unique technical challenges that prevent the direct application of existing algorithms. Extending prior work on threshold-based algorithms, we introduce double-threshold algorithms for both variants of this problem. We further show that the competitive ratios achieved by these algorithms are the best achievable by any deterministic online algorithm. Finally, we empirically validate our proposed algorithm through case studies on the application of carbon-aware load shifting using real carbon trace data and existing baseline algorithms.
Who's Got My Back? Measuring the Adoption of an Internet-wide BGP RTBH Service
Authors: Anghel Radu , Zhauniarovich Yury , Gañán Carlos
Published: June 2024

Distributed Denial-of-Service (DDoS) attacks continue to threaten the availability of Internet-based services. While countermeasures exist to decrease the impact of these attacks, not all operators have the resources or knowledge to deploy them. Unwanted Traffic Removal Service (UTRS), being one of the oldest community-based anti-DDoS services aims at mitigating major DDoS attacks through the Border Gateway Protocol (BGP).

In this paper we develop and evaluate a methodology to automatically detect UTRS participation in the wild. To this end, we deploy a measurement infrastructure and devise a methodology to detect UTRS-based traffic blocking. Using this methodology, we conducted a longitudinal analysis of UTRS participants over ten weeks. Our results show that at any point in time, there were 562 participants, including multihomed, stub, transit, and IXP ASes. Moreover, we surveyed 245 network operators to understand why they would (not) join UTRS. Results show that threat and coping appraisal significantly influence the intention to participate in UTRS.
Land Bridges and Rafting Theories to Explain Terrestrial-Vertebrate Biodiversity on Madagascar
Authors: Ali Jason R. , Hedges S. Blair
Published: June 2024

Madagascar's celebrated land-vertebrate assemblage has long been studied and discussed. How the ancestors of the 30 different lineages arrived on the island, which has existed since 85 Mya and is separated from neighboring Africa by 430 km of water, is a deeply important question. Did the colonizations take place when the landmass formed part of Gondwana, or did they occur later and involve either now-drowned causeways or overwater dispersal (on vegetation rafts or by floating/swimming)? Following a historical review, we appraise the geological–geophysical evidence and the faunal-suite colonization record. Twenty-six of the clades are explained by temporally stochastic overwater dispersals, spanning 69–0 Mya, while two others are considered Gondwanan vicariant relicts. Due to a lack of information, the remaining two groups cannot be evaluated. The findings thus appear to resolve a debate that has rumbled along, with sporadic eruptions, since the mid-1800s.
Expanding the Plant Virome: Umbra-Like Viruses Use Host Proteins for Movement
Authors: Simon Anne E. , Quito-Avila Diego F. , Bera Sayanta
Published: June 2024

Before the very recent discovery of umbra-like viruses (ULVs), the signature defining feature of all plant RNA viruses was the encoding of specialized RNA-binding movement proteins (MPs) for transiting their RNA genomes through gated plasmodesmata to establish systemic infections. The vast majority of ULVs share umbravirus-like RNA-dependent RNA polymerases and 3′-terminal structures, but they differ by not encoding cell-to-cell and long-distance MPs and by not relying on a helper virus for trans-encapsidation and plant-to-plant transmission. The recent finding that two groups of ULVs do not necessarily encode MPs is expanding our understanding of the minimum requirements for modern plant RNA viruses. ULV CY1 from citrus uses host protein PHLOEM PROTEIN 2 (PP2) for systemic movement, and related ULVs encode a capsid protein, thereby providing an explanation for the lack of helper viruses present in many ULV-infected plants. ULVs thus resemble the first viruses that infected plants, which were likely deposited from feeding organisms and would have similarly required the use of host proteins such as PP2 to exit initially infected cells.
The Role of Colon in Isolated Intestinal Transplantation: Description of 4 Cases
Authors: Di Cocco Pierpaolo , Bencini Giulia , Martinino Alessandro , Petrochenkov Egor , Akshelyan Stepan , Yoshikawa Kentaro , Spaggiari Mario , Almario-Alvarez Jorge , Tzvetanov Ivo , Benedetti Enrico
Published: June 2024

Intra‐abdominal desmoid tumors are a rare and complex clinical problem. These tumors are locally invasive, and surgical ablation represents the mainstay of treatment. When localized at the root of the mesentery, their resection may require extensive excision of the intestine resulting in intestinal failure and life‐long total parenteral nutrition. Intestinal transplantation, either autotransplantation or allotransplantation, has been used as a viable option to treat this group of patients. Herein, we describe a series of 4 patients with unresectable intra‐abdominal desmoid tumor who underwent cadaveric isolated intestinal and ascending colon transplantation.
Late‐Onset Maculopapular Eruptions Associated with Elevated Varicella‐Zoster Virus Complement‐Fixing Antibody Titers following BNT162b2 mRNA COVID‐19 Vaccination in Older Adult Japanese Patients: A Cross‐Sectional Study
Authors: Oka Masahiro , Fujii Yosuke , Murakami Sae
Published: June 2024

Diverse cutaneous adverse reactions associated with the messenger RNA‐based BNT162b2 coronavirus disease 2019 (COVID‐19) vaccine have been reported, usually developing within 3 weeks after the first vaccination. However, the long‐term cutaneous effects of this vaccine remain poorly understood. We hypothesized that the BNT162b2 vaccine might trigger late‐onset (>4 weeks after the first dose) maculopapular eruptions associated with elevated varicella‐zoster virus (VZV) complement‐fixing antibody (VZV‐CF Ab) titers indicative of recent subclinical VZV reactivation. Therefore, we conducted a hospital‐based cross‐sectional study at the Dermatology Department of Kita‐Harima Medical Center, Ono City, Japan, between July 1, 2021, and June 30, 2022, to investigate the correlations among the BNT162b2 vaccine, maculopapular eruptions, and VZV‐CF Ab titers. Fifteen eligible patients (EPs) who experienced maculopapular eruptions on the trunk and extremities no earlier than 4 weeks after the first BNT162b2 vaccine dose and 12 control patients (CPs) were enrolled. The mean age of EPs and CPs was 73.7 and 77.6 years, respectively, and the median interval between the first BNT162b2 vaccination and onset of maculopapular eruptions was 90 days. The median VZV‐CF Ab titer of EPs was significantly higher than that of CPs (×8 vs. ×4). Although people of all ages, except children aged ≤12 years, received BNT162b2 vaccinations, all EPs were aged ≥57 years. All EPs presented between July 2021 and March 2022. There were no EPs from April 2022 to December 2023. These results suggest that the BNT162b2 vaccine triggers elevated VZV‐CF Ab titer‐associated maculopapular eruptions as late‐onset cutaneous adverse reactions in older adults. Furthermore, the observation that two EPs concurrently experienced delayed large local reactions, also known as COVID arm, along with maculopapular eruptions, supported our hypothesis. Our findings may improve the diagnosis of BNT162b2 vaccine‐triggered elevated VZV‐CF Ab titer‐associated late‐onset maculopapular eruptions and facilitate further investigation of diverse BNT162b2 vaccine‐induced adverse events.
Cardiovascular and Vector‐Cardiographic Effects of Articaine Anesthesia with Epinephrine
Authors: Pökel Christoph , Schulze Antina , Busse Martin
Published: June 2024

The aim was to investigate the vector‐cardiographic effects in patients submitted to dental extraction under local anesthesia. Twenty‐one patients aged 36.6 ± 12.4 years with a clinical and radiographic indication of mandibular or maxillary tooth extraction were enrolled. The intervention was a local or mandibular nerve block anesthesia with 4% articaine hydrochloride containing epinephrine (1 : 100,000; 40 mg/ml + 10 μg/ml). Blood pressure (BP), heart rate (HR), pulse wave transit time, and vector‐cardiography data were recorded throughout 3 min before and 5 min after injection. QRS‐ and T‐wave area under the curve (QRSAUC/TAUC) were calculated from the X/Y/Z QRS‐vector or T‐vector. T‐wave amplitude (TAM), TAUC values, and diastolic BP decreased, and HR significantly increased 4 min after injection. A transient moderate HR drop and a corresponding small increase in TAM and TAUC immediately after the injection procedure may be explained by a decreased sympathetic tone due to psychological relief. In dental anesthesia, the systemic epinephrine effects are represented by a decrease in TAUC. These effects are most pronounced in the X‐ and Y‐leads. The 3D determination of vector planes or amplitudes is a simple method to register the sympathetic tone in local anesthesia independently of possible effects on T‐wave characteristics in single leads. In conclusion, T‐wave determination may help to detect even small increases in systemic adrenaline concentration in case of accidental intravascular injection. At the same time, full rhythm and spatial ischemia control is provided.
Figure S2 from Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E.
Published: June 2024

Figure S2
Supplementary Figure S1 from A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies
Authors: Kalogera Eleftheria , Nevala Wendy K. , Finnes Heidi D. , Suman Vera J. , Schimke Jill M. , Strand Carrie A. , Kottschade Lisa A. , Kudgus Rachel A. , Buhrow Sarah A. , Becher Laura R. , Geng Liyi , Glaser Gretchen E. , Grudem Megan E. , Jatoi Aminah , Klampe Carolyn M. , Kumar Amanika , Langstraat Carrie L. , McWilliams Robert R. , Wahner Hendrickson Andrea E. , Weroha S. John , Yan Yiyi , Reid Joel M. , Markovic Svetomir N. , Block Matthew S.
Published: June 2024

Paclitaxel Pharmacokinetics
PlexinB1 Inactivation Reprograms Immune Cells in the Tumor Microenvironment, Inhibiting Breast Cancer Growth and Metastatic Dissemination
Authors: Franzolin Giulia , Brundu Serena , Cojocaru Carina F. , Curatolo Aurora , Ponzo Matteo , Mastrantonio Roberta , Mihara Emiko , Kumanogoh Atsushi , Suga Hiroaki , Takagi Junichi , Tamagnone Luca , Giraudo Enrico
Published: June 2024

Semaphorin–plexin signaling plays a major role in the tumor microenvironment (TME). In particular, Semaphorin 4D (SEMA4D) has been shown to promote tumor growth and metastasis; however, the role of its high-affinity receptor Plexin-B1 (PLXNB1), which is expressed in the TME, is poorly understood. In this study, we directly targeted PLXNB1 in the TME of triple-negative murine breast carcinoma to elucidate its relevance in cancer progression. We found that primary tumor growth and metastatic dissemination were strongly reduced in PLXNB1-deficient mice, which showed longer survival. PLXNB1 loss in the TME induced a switch in the polarization of tumor-associated macrophages (TAM) toward a pro-inflammatory M1 phenotype and enhanced the infiltration of CD8+ T lymphocytes both in primary tumors and in distant metastases. Moreover, PLXNB1 deficiency promoted a shift in the Th1/Th2 balance of the T-cell population and an antitumor gene signature, with the upregulation of Icos, Perforin-1, Stat3, and Ccl5 in tumor-infiltrating lymphocytes (TILs). We thus tested the translational relevance of TME reprogramming driven by PLXNB1 inactivation for responsiveness to immunotherapy. Indeed, in the absence of PLXNB1, the efficacy of anti-PD-1 blockade was strongly enhanced, efficiently reducing tumor growth and distant metastasis. Consistent with this, pharmacological PLXNB1 blockade by systemic treatment with a specific inhibitor significantly hampered breast cancer growth and enhanced the antitumor activity of the anti-PD-1 treatment in a preclinical model. Altogether, these data indicate that PLXNB1 signaling controls the antitumor immune response in the TME and highlight this receptor as a promising immune therapeutic target for metastatic breast cancers.
Knocking Out CD70 Rescues CD70-Specific NanoCAR T Cells from Antigen-Induced Exhaustion
Authors: De Munter Stijn , Buhl Juliane L. , De Cock Laurenz , Van Parys Alexander , Daneels Willem , Pascal Eva , Deseins Lucas , Ingels Joline , Goetgeluk Glenn , Jansen Hanne , Billiet Lore , Pille Melissa , Van Duyse Julie , Bonte Sarah , Vandamme Niels , Van Dorpe Jo , Offner Fritz , Leclercq Georges , Taghon Tom , Depla Erik , Tavernier Jan , Kerre Tessa , Drost Jarno , Vandekerckhove Bart
Published: June 2024

CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy for the treatment of both solid and liquid malignancies. However, the functionality of CD70-specific CAR T cells is modest. We optimized a CD70-specific VHH-based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models in vitro, using co-cultures of CD70-specific nanoCAR T cells with malignant rhabdoid tumor organoids, and in vivo, using a diffuse large B-cell lymphoma patient-derived xenograft (PDX) model. Although the nanoCAR T cells were highly efficient in organoid co-cultures, they showed only modest efficacy in the PDX model. We determined that fratricide was not causing this loss in efficacy but rather CD70 interaction in cis with the nanoCAR-induced exhaustion. Knocking out CD70 in nanoCAR T cells using CRISPR/Cas9 resulted in dramatically enhanced functionality in the diffuse large B-cell lymphoma PDX model. Through single-cell transcriptomics, we obtained evidence that CD70 knockout CD70-specific nanoCAR T cells were protected from antigen-induced exhaustion. In addition, we demonstrated that wild-type CD70-specific nanoCAR T cells already exhibited signs of exhaustion shortly after production. Their gene signature strongly overlapped with gene signatures of exhausted CAR T cells. Conversely, the gene signature of knockout CD70-specific nanoCAR T cells overlapped with the gene signature of CAR T-cell infusion products leading to complete responses in chronic lymphatic leukemia patients. Our data show that CARs targeting endogenous T-cell antigens negatively affect CAR T-cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target.
Middle Cerebral Artery Doppler before and after Fetal Spina Bifida Repair: An Indirect Sign of Hindbrain Compression and Decompression?
Authors: Vonzun Ladina , Ruegg Ladina , Zepf Julia , Strübing Nele , Grehten Patrice , Meuli Martin , Mazzone Luca , Moehrlen Ueli ,   Spina Bifida Study Group Zurich, Ochsenbein-Koelble Nicole
Published: June 2024

Introduction: Reduced middle cerebral artery resistance indices (MCA-RI) in fetuses with spina bifida (fSB) are commonly observed. Compression of neuronal pathways in the brainstem due to hindbrain herniation (HH) and disturbed cerebrospinal fluid circulation likely cause an imbalance of the autonomic nervous system. This may increase systemic vasoconstriction and compensatory increase cerebral vasodilation (like brain sparing). The aim of this study was to systematically analyze all fetal MCA-RI before and after fSB repair and to compare their correlation with the presence and postsurgical resolution of HH. Methods: 173 patients were included. Standardized ultrasound examinations including MCA and umbilical artery (UA) Doppler as well as assessment of HH presence and regression were performed. Fetuses with MCA-RI <5th percentile (P) before fetal surgery were compared to the group with normal MCA-RI and correlated to the presence of HH before and its regression after fSB repair. Results: 30% (49/161) fetuses showed RI’s <5th P before fSB repair. All fetuses had normal UA-RI. 99.4% of fetuses (160/161) showed normal of MCA-RI before delivery. Normalization occurred within a mean of 1.3 ± 1.2 weeks. HH regression was observed in 97% in the group with normal MCA-RI and in 96% in the group with MCA-RI <5th P before surgery (p = 0.59). Time lapse to HH regression after fSB repair was 1.8 ± 1.7 and 1.9 ± 1.6 weeks, respectively. Conclusion: In fetuses with MCA-RIs <5 P before fSB repair, a parallel timely course of MCA-RI normalization and HH regression was noted. To suggest common pathogenic factor(s), more studies are needed. However, normalization of the fetal cerebral circulation could be a further benefit of fSB repair.
Perspectives in Managing Kidney Disease and Atherosclerotic Cardiovascular Disease
Authors: Namvar Tarlan , Cavender Matthew A. , Miller Eden , Mehanna Sherif , Ochsner Reese , Raj Dominic S.
Published: June 2024

Introduction: Chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) share a complex and dependent link with each other and other cardiometabolic conditions. Currently, there is insufficient data regarding patient and provider perceptions about this important clinical overlap. This study sought to evaluate healthcare provider (HCP) and patient attitudes and perceptions about CKD and ASCVD, including risk, diagnosis, and management of both conditions.
Methods: Cross-sectional surveys of 58 nephrologists and 74 cardiologists who treat patients with CKD and ASCVD and 195 patients who self-reported having CKD and ASCVD were conducted in the US between May and June 2021.
Results: Most nephrologists agreed that the presence of cardiometabolic comorbidities increased patients’ risk of developing CKD; 86% agreed that type 2 diabetes (T2D) increased the risk, and 67% agreed that ASCVD increased the risk. However, only 52% of the nephrologists reported they typically discuss the risk of developing CKD with patients prior to diagnosing them. Slightly more than one-third of patients (35%) reported their HCP discussed other conditions’ impact on the development of CKD; of all HCPs surveyed, nephrologists were the least likely to discuss CKD risk with their patients. Most nephrologists (83%) also reported they recommended lifestyle modification to patients; however, only about half of patients (53%) reported they were currently using a lifestyle change to treat CKD and/or ASCVD.
Conclusions: Although CKD and ASCVD are known to have a bidirectional relationship, HCPs in our study did not report routinely educating patients about the risk of developing one or both conditions. As HCPs with perhaps the deepest understanding of the interplay between CKD and cardiorenal comorbidities, nephrologists are well positioned to help patients understand the link between cardiovascular and renal health, help identify strategies to limit risk, and appropriately treat the conditions.
Efficiency in academic evaluation: data envelopment analysis systematic review
Authors: Razi Nor Faezah Mohamad , Baharun Norhayati , Masrom Suraya
Published: June 2024

Education 5.0@UiTM is transforming Universiti Teknologi MARA (UiTM). This new approach emphasizes flexible learning paths that teach life and cross-disciplinary skills. To make higher education future-ready, universities must adapt fast to the significant global and technical changes caused by the 4th Industrial Revolution and transition from content-based to individualized learning. To ensure students meet Education 5.0@UiTM standards and corporate needs, the evaluation process must be reviewed. Competency-based academic achievement evaluation outperforms grades. This assessment is rarely systematically analyzed. This study was conducted to thoroughly explore the selection of input and output factors in determining student achievement efficiency using the data envelopment analysis (DEA) approach. The study reviewed publications from Scopus, Google Scholar, and Science Direct and found six themes for input variables: human resources, facilities condition and equipment, finance, curriculum, students characteristics, and community resources. output variables included student achievement, satisfaction, graduation rate, employment, research, and community resources. In DEA analysis, input and output selection affects scope, aim, production frontier, efficiency scores, accuracy and completeness. So, characterizing student achievement requires choosing relevant input and output variables. This study can enhance student evaluation processes to prepare college graduates for the next industrial revolution.
Exploring factors of international students’ satisfaction: a case of Islamic universities in Malaysia
Authors: Amzat Ismail Hussein , Kassim Noorafini , Yusuf Byabazaire , Hamed Alyahmadi , Juping Qiao , Khofiati Ani
Published: June 2024

No qualms, international student mobility has become a source of income for countries around the world. International students become more mobile, contributing to the university’s growth and diversity. It has also created competition by making higher institutions around the world develop strategies to attract them. This study explores the factors that lead to satisfaction among international students and the item indicator. This study is quantitative in nature, using a survey to collect the data. The population consists of international students from Asia, Africa, Europe, and Latin America at the leading Islamic universities in Malaysia. A total of 211 international students participated in the study. Ruffola Noel Levitz’s student satisfaction inventory, 2017 was used as an instrument, and a measurement model from SEM was applied to analyze the data. From the measurement model results, student-centeredness was ranked as the leading factor influencing international student satisfaction; followed instructional effectiveness. The main prediction or leading factor to improve international student satisfaction is to ensure international students’ positive feelings of self-belonging in Islamic universities in Malaysia. Improving instruction and service are also suggested to meet international student expectations and satisfaction. However, there is a scarcity of research conducted or published about Islamic universities worldwide, making Islamic universities neglected and difficult to find literature about.