bluuebunny/crossref_metadata_2025 huggingface dataset:
Bictegravir/emtricitabine/tenofovir alafenamide in adults with HIV‐1 and end‐stage kidney disease on chronic haemodialysis
Authors: Eron Joseph J. , Ramgopal Moti , Osiyemi Olayemi , Mckellar Mehri , Slim Jihad , DeJesus Edwin , Arora Priyanka , Blair Christiana , Hindman Jason T. , Wilkin Aimee
Published: October 2024

Introduction

Treatment for people with HIV‐1 and end‐stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose‐adjusted regimens, with limited data on the use of a single‐tablet regimen in this population. Our aim was to assess the efficacy and safety of once‐daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV‐1 and ESKD on HD.

Methods

We performed an open‐label extension (OLE) of an open‐label, multicentre, single‐group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV‐1 with virological suppression. Participants switched to elvitegravir/cobicistat/F/TAF (E/C/F/TAF) 150/150/200/10 mg for 96 weeks, following which a subgroup of US participants entered an OLE phase in which they switched to B/F/TAF 50/200/25 mg for 48 weeks, returning for study visits at weeks 4 and 12, and every 12 weeks thereafter. Study assessments included virological response, safety and pharmacokinetic analysis of BIC.

Results

Ten participants entered the OLE (median age, 55 years). Virological suppression (HIV‐1 RNA <50 copies/mL) was maintained in all participants over 48 weeks of B/F/TAF treatment. B/F/TAF was well tolerated, with no treatment discontinuations. Mean BIC trough concentrations were lower than those previously reported for people with HIV‐1 with normal kidney function, but remained four‐ to seven‐fold higher than the established protein‐adjusted 95% effective concentration against wild‐type HIV‐1.

Conclusion

These findings support the use of the once‐daily B/F/TAF single‐tablet regimen for people with HIV‐1 and ESKD on HD. This regimen offers a convenient treatment option for this population as it reduces the need for dose adjustment, eases pill burden and avoids potential drug–drug interactions associated with alternatives that may impact individuals on multiple medications or awaiting transplantation.
Social Workers' Experiences of Working With Support Workers in Services for Adults With Intellectual Disabilities in Hong Kong
Authors: Xun Kangwei , Jiao Ruoshui , Deng Yunxue
Published: October 2024

Background

Services for adults with intellectual disabilities in Hong Kong have a hierarchical staffing structure. Professional social workers, who performed as mid‐level employees, work with frontline support workers to deliver services to clients.

Methods

This qualitative study explored social workers' experiences of working with support workers through in‐depth interviews with 13 participants.

Findings

The study revealed that social workers perceived a significant variation between themselves and support workers in terms of working motivation, values and attitudes towards clients with intellectual disabilities. Despite the hierarchical relationships, social workers and support workers share the power of service decision‐making. Social workers used firm and gentle approaches to facilitate changes in practices to uphold service values. These findings were compared with Western literature on this topic, indicating similarities and differences.

Conclusion

The organisations need to facilitate an effective collaboration between social workers and support workers to enhance the quality of services for adults with intellectual disabilities in Hong Kong.
Constituents From Brazilian Propolis Against Edwardsiella ictaluri and Flavobacterium covae, Two Bacteria Affecting Channel Catfish (Ictalurus punctatus)
Authors: Ribeiro Victor P. , Bastos Jairo K. , Harries Marcuslene D. , Page Phaedra N. , Techen Natascha , Meepagala Kumudini M.
Published: October 2024

Edwardsiella ictaluri and Flavobacterium covae are two bacteria species that cause diseases in farm‐raised channel catfish (Ictalurus punctatus) that cause heavy economic damage to the aquaculture industry, particularly to the channel catfish farming. In search for environmentally benign antibacterial compounds active against E. ictaluri and F. covae, we investigated the constituents isolated from Brazilian red, brown and green propolis. We have also synthetically modified active constituents to see if lipophilicity plays a role in enhancing antibacterial activities. Vestitol, neovestitol and methylvestitol were found to be the active constituents with minimum inhibitory concentration (MIC) relative to drug control florfenicol (RDCF) values (MIC−RDCF) of 7.6, 7.6 and 7.9 mg/L, respectively, against F. covae. The activity against E. ictaluri was not significant.
Effects of In Ovo Administration of Freeze‐Dried Royal Jelly on Hatchability, Blood Parameters, and Organ Weights of Day‐Old Chicks
Authors: Hassan Mohamed I. , Hassan Saber S. , Soliman Farid N. K. , Khalil Mohamed H.
Published: October 2024

Royal jelly renowned for its robust nutritional, functional, and biological properties, is a pivotal product derived from honeybees. The purpose of this investigation was to assess the theory that in ovo injection of freeze‐dried royal jelly (FDRJ) solutions at varying concentrations can influence the hatchability, blood properties and hatching characteristics of day‐old chicks. A total of 480 eggs (54.81 ± 0.187 g) were allocated into four experimental groups: negative control (NC), without injection, positive control (PC), administered with regular saline, a low FDRJ dose group (9 mg/egg), and a high FDRJ dose group (18 mg/egg). The in ovo injections were administered on Day 18 of incubation, and the experiment was subsequently continued until the incubation period concluded at 21 days. Results revealed that the lower FDRJ dose (9 mg/egg) significantly improved hatchability percentages compared to other treatments. Conversely, the higher FDRJ dose (18 mg/egg) and control groups (NC and PC) resulted in significantly higher chick yield percentages than the lower FDRJ and PC groups. The NC group showed the supreme yolk sac (YS) percentage, whereas the yolk‐free body mass (YFBM) percentages displayed an inverse trend. Furthermore, the in ovo FDRJ injection did not affect haematological values or the relative organ weight of day‐old chicks. In conclusion, in ovo FDRJ injection demonstrated beneficial effects on hatchability and chick weight, as evidenced by the studied parameters.
Sigmodontinae rodents as potential reservoirs for Borrelia burgdorferi sensu lato in the Delta and Paraná Islands ecoregion, Argentina
Authors: Barolin Johann , Antoniazzi Leandro Raul , Colombo Valeria Carolina , Beldomenico Pablo Martin , Monje Lucas Daniel
Published: October 2024

The Borrelia burgdorferi sensu lato (s.l.) complex includes a group of spirochete bacteria that are involved in transmission cycles with vertebrates and the ticks associated with them. Rodents play an essential role in the ecoepidemiology of Borrelia, acting as reservoirs for the bacteria and hosts for ticks. To identify potential reservoir vertebrate hosts of Borrelia spirochetes in Argentina, we conducted molecular analyses on tissues obtained from a population of Sigmodontinae rodents inhabiting the Delta and Parana Islands ecoregion. We report the presence of B. burgdorferi s.l. complex genotypes infecting Akodon azarae and Oxymycterus rufus in this ecoregion. Phylogenetic analysis revealed at least three flaB haplotypes related to ‘Candidatus Borrelia paulista’ and Borrelia sp. strain Pampa from Brazil and to several Borrelia haplotypes from Uruguay. Additionally, we identified different alleles of the plasmid‐borne gene ospC in B. burgdorferi s.l. infecting A. azarae and Ox. rufus. The ospC allele present in Borrelia from Ox. rufus was also detected in Borrelia from Oligoryzomys mattogrossae, indicating the ability of Borrelia harbouring this ospC allele to infect multiple Sigmodontinae species, whereas the ospC allele from Borrelia infecting A. azarae represents a novel variant. Further research is needed to determine host specificity of ospC alleles present in South America.
Refining our understanding of the diversity of plant specialised metabolites
Authors: Speed Mike , Ruxton Graeme
Published: October 2024

This article is a Commentary on Wittmann & Bräutigam (2025), 245: 1302–1314.
Taxonomic revision of Physalis species (Solanaceae) in Korea
Authors: KANG Eun Su , KIM Jin Suk , LEE Man Kyu , LEE Kang-Hyup , SON Dong Chan
Published: October 2024

The records of various Physalis species in Korea along with unclear descriptions and the use of multiple Korean names for a single species have led to confusion with regard to species identification in this genus. Therefore, the aim of the present study was to identify and characterize Physalis species distributed in the Republic of Korea through a literature review, specimen observations, and field surveys. Five Physalis species were found to be distributed in the Republic of Korea: P. angulata, P. lagascae, P. longifolia, P. philadelphica, and P. pubescens. Additionally, it was confirmed that part of P. fauriei and P. repens can be considered to be synonyms of P. lagascae, whereas the other part of P. fauriei is regarded as synonyms of P. pubescens. The species can be distinguished based on their life forms, presence of rhizomes, leaf serration depth, arrangement of hairs on the calyx, corolla diameter and spot color, and fruit shape and ridge number. Physalis angulata and P. pubescens are distributed in various regions, primarily in the southern and western parts of the Republic of Korea. In contrast, P. lagascae is found exclusively in limited regions of Jeju-do, Chungcheongbuk-do, and Gangwon-do, with P. longifolia and P. philadelphica found only in Yeongwol-gun of Gangwon-do. This study provides revised descriptions and an identification key along with photographs and distribution information for Physalis species in the Republic of Korea.
Development and characterization of 15 polymorphic microsatellite markers for Hepatica insularis (Ranunculaceae) endemic to the Korean Peninsula
Authors: HAN Eun-Kyeong , LIM Da-Hyun , CHO Won-Bum , GANTSETSEG Amarsanaa , JANG Young-Jong , PARK Jong-Soo , LEE Jung-Hyun
Published: October 2024

Hepatica insularis Nakai, a perennial herb endemic to warm-temperate regions on the Korean Peninsula, has been a subject of taxonomic debate due to its morphological similarities with Hepatica asiatica Nakai. To address the taxonomic ambiguity and provide evolutionary insights into H. insularis, we developed 15 polymorphic microsatellite markers. Of these, eight markers were successfully cross-amplified in H. asiatica, demonstrating their broader applicability. The markers exhibited high levels of polymorphism, with the number of alleles per locus ranging from two to eleven. The expected heterozygosity (HE) and observed heterozygosity (HO) values ranged from 0.180 to 0.802 and from 0.000 to 0.933, respectively. The developed markers will serve as a valuable tool for future phylogeographic studies aiming to understand the genetic structure and diversity of H. insularis and related taxa.
Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes
Authors: Chen Xi Dawn , Chen Zeyu , Wythes George , Zhang Yifan , Orr Benno C. , Sun Gary , Chao Yu-Kai , Navarro Torres Andrea , Thao Ka , Vallurupalli Mounica , Sun Jing , Borji Mehdi , Tkacik Emre , Chen Haiqi , Bernstein Bradley E. , Chen Fei
Published: October 2024

Deciphering the context-specific relationship between sequence and function is a major challenge in genomics. Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited. Here we present a programmable platform for long-range, locus-specific hypermutation called helicase-assisted continuous editing (HACE). HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large (>1000–base pair) genomic intervals. We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1 (MEK1) that confer kinase inhibitor resistance, to dissect the impact of individual variants in splicing factor 3B subunit 1 (SF3B1)–dependent missplicing, and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69. HACE provides a powerful tool for investigating coding and noncoding variants, uncovering combinatorial sequence-to-function relationships, and evolving new biological functions.
Evidence of a European seed dispersal crisis
Authors: Mendes Sara Beatriz , Olesen Jens Mogens , Memmott Jane , Costa José Miguel , Timóteo Sérgio , Dengucho Ana Laura , Craveiro Leonardo , Heleno Ruben
Published: October 2024

Seed dispersal is crucial for ecosystem persistence, especially in fragmented landscapes, such as those common in Europe. Ongoing defaunation might compromise effective seed dispersal, but the conservation status of pairwise interactions remains unknown. With a literature review, we reconstructed the first European-wide seed dispersal network and evaluated the conservation status of interactions by assessing each interacting partner’s IUCN (International Union for Conservation of Nature) conservation status and population trends. We found that a third of the disperser species and interactions face potential extinction and that 30% of the plant species have most of their dispersers threatened or declining. Our study reveals a developing seed dispersal crisis in Europe and highlights large knowledge gaps regarding the dispersers and conservation status of zoochorous plants, urging further scrutiny and action to conserve the seed dispersal service.
Plasmodium falciparum
protein phosphatase PP7 is required for early ring-stage development
Authors: Patel Avnish , Fréville Aline , Rey Joshua A. , Flynn Helen R. , Koussis Konstantinos , Skehel Mark J. , Blackman Michael J. , Baker David A.
Published: October 2024

We previously reported that the
Plasmodium falciparum
putative serine/threonine protein phosphatase 7 (PP7) is a high-confidence substrate of the cAMP-dependent protein kinase (PKA). Here we explore the function of PP7 in asexual
P. falciparum
blood stage parasites. We show that conditional disruption of PP7 leads to a severe growth arrest. We show that PP7 is a calcium-dependent phosphatase that interacts with calmodulin and calcium-dependent protein kinase 1 (CDPK1), consistent with a role in calcium signaling. Notably, PP7 was found to be dispensable for erythrocyte invasion, but was crucial for ring-stage development, with PP7-null parasites arresting shortly following invasion and showing no transition to ameboid forms. Phosphoproteomic analysis revealed that PP7 may regulate certain PKAc substrates. Its interaction with calmodulin and CDPK1 further emphasizes a role in calcium signaling, while its impact on early ring development and PKAc substrate phosphorylation underscores its importance in parasite development.

IMPORTANCE

Plasmodium falciparum
causes malaria and is responsible for more than 600,000 deaths each year. Although effective drugs are available to treat disease, the spread of drug-resistant parasites endangers their future efficacy. It is hoped that a better understanding of the biology of malaria parasites will help us to discover new drugs to tackle the resistance problem. Our work is focused on the cell signaling mechanisms that control the development of the parasite throughout its complex life cycle. All signal transduction pathways are ultimately regulated by reversible protein phosphorylation by protein kinase and protein phosphatase enzymes. In this study, we investigate the function of calcium-dependent protein phosphatase PP7 and show that it is essential for the development of ring-stage parasites following the invasion of human erythrocytes. Our results contribute to the understanding of the erythrocytic stages of the parasite life cycle that cause malaria pathology.
Integrated analysis of microbiome and metabolome reveals signatures in PDAC tumorigenesis and prognosis
Authors: Fang Yuan , Liu Xiaohong , Ren Jie , Wang Xing , Zhou Feihan , Huang Shi , You Lei , Zhao Yupei
Published: October 2024

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of
Staphylococcus aureus
,
Cutibacterium acnes,
and
Cutibacterium granulosum
was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of
Ralstonia pickettii_B
was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine.

IMPORTANCE

We conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens
Staphylococcus aureus
,
Cutibacterium acnes
, and
Cutibacterium granulosum
were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of
Ralstonia pickettii_B
. Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria.
Interplay between a polerovirus and a closterovirus decreases aphid transmission of the polerovirus
Authors: Khechmar Souheyla , Chesnais Quentin , Villeroy Claire , Brault Véronique , Drucker Martin
Published: October 2024

Multi-infection of plants by viruses is very common and can change drastically infection parameters such as virus accumulation, distribution, and vector transmission. Sugar beet is an important crop that is frequently co-infected by the polerovirus beet chlorosis virus (BChV) and the closterovirus beet yellows virus (BYV), both vectored by the green peach aphid (
Myzus persicae
). These phloem-limited viruses are acquired while aphids ingest phloem sap from infected plants. Here we found that co-infection decreased transmission of BChV by ~50% but had no impact on BYV transmission. The drastic reduction of BChV transmission was due to neither lower accumulation of BChV in co-infected plants nor reduced phloem sap ingestion by aphids from these plants. Using the signal amplification by exchange reaction fluorescent
in situ
hybridization technique on plants, we observed that 40% of the infected phloem cells were co-infected and that co-infection caused redistribution of BYV in these cells. The BYV accumulation pattern changed from distinct intracellular spherical inclusions in mono-infected cells to a diffuse form in co-infected cells. There, BYV co-localized with BChV throughout the cytoplasm, indicative of virus-virus interactions. We propose that BYV-BChV interactions could restrict BChV access to the sieve tubes and reduce its accessibility for aphids and present a model of how co-infection could alter BChV intracellular movement and/or phloem loading and reduce BChV transmission.

IMPORTANCE

Mixed viral infections in plants are understudied yet can have significant influences on disease dynamics and virus transmission. We investigated how co-infection with two unrelated viruses, BChV and BYV, affects aphid transmission of the viruses in sugar beet plants. We show that co-infection reduced BChV transmission by about 50% without affecting BYV transmission, despite similar virus accumulation rates in co-infected and mono-infected plants. Follow-up experiments examined the localization and intracellular distribution of the viruses, leading to the discovery that co-infection caused a redistribution of BYV in the phloem vessels and altered its repartition pattern within plant cells, suggesting virus-virus interactions. In conclusion, the interplay between BChV and BYV affects the transmission of BChV but not BYV, possibly through direct or indirect virus-virus interactions at the cellular level. Understanding these interactions could be crucial for managing virus propagation in crops and preventing yield losses.
Equilibrium Figures of Two Liquid Masses with Synchronous Rotation. Dynamics of Double Asteroid (190166) 2005 UP156
Authors: Kondratyev B. P.
Published: October 2024

The problem of equilibrium figures of two liquid masses in a state of tidal mutual capture is posed and solved. The condition of complete synchronous (orbital plus spin) rotation is satisfied in the system, and both bodies have the same masses and congruent ellipsoidal surfaces. For each figure, besides its own gravity and centrifugal forces, the attraction from the second body is taken into account in the tidal approximation. The spatial form of equilibrium figures as triaxial ellipsoids is found by an analytical and numerical method. The spin rotation of ellipsoidal equilibrium figures is established to occur not around small axes, as is usually assumed, but around the middle axes of the ellipsoids. This method is used to study the binary asteroid (190166) 2005 UP156, which approximately satisfies the initial conditions of the problem. The study showed that with the parameters known today, the system of two asteroids (190166) 2005 UP156 is nonequilibrium.
Conducting research “in a good way”: relationships as the foundation of research
Authors: Gordon (Iñupiaq) Heather Sauyaq Jean , Around Him Deana
Published: October 2024

Indigenous Peoples across the world have a history of colonization that continues today. Additionally, Indigenous Peoples have experienced harm from research. This paper explores conducting research with Indigenous Peoples in a “good way”. Relationships built prior to and throughout the research process are foundational to conducting research in a good way, meaning the research respects and recognizes Indigenous inherent sovereignty; is culturally centered; relational; participatory; asset based; anti-racist; decolonizing; trauma-informed; survivor-centered; and engages free, prior, and informed, consent and Indigenous methodologies. This approach draws on the strength of Indigenous cultures, centering Indigenous Knowledges, and working toward Indigenous goals. A case study details the use of an Indigenous relational theoretical framework in practice, building life-long relationships through a research project that adapted a historically non-Indigenous methodology (ethnographic futures research) through a self-determining, participatory, and co-production project with the Ninilchik Village Tribe in Alaska. Our discussion broadens the application of this approach to research in any context with Indigenous children, youth, families, and Elders, reminding the reader that decolonization is not a metaphor but requires actual change in researchers, institutions, and funders.
Production and measurement of a stellar neutron spectrum at 30 keV
Authors: Praena Javier , Verdera Antònia , López Javier García , Martín-Hernández Guido
Published: October 2024

A few years ago, we theoretically studied the production of a stellar neutron spectrum at kT = 30 keV using a shaped proton beam impinging on a thick lithium target. Here, we first measure the proton distribution to better control the produced neutron spectrum. Then, we measure the forward-emitted angle-integrated neutron spectrum of the 7Li(p,n)7Be reaction via time-of-flight neutron spectrometry with such proton distribution. The result resembles a stellar neutron spectrum at kT = 30 keV. This method avoids in activation experiments the need for spectrum correction. In the case of spherical samples, no knowledge of the cross-section of the isotope being measured by activation would be necessary. Therefore, the present method is of interest for isotopes with unknown or poorly known cross-sections, such as branching points in astrophysics. The key point of our method is the experimental control of the proton distribution that impinges on the lithium target.
Confinement and deconfinement in gauge theories: A quantum field theory
Authors: Balachandran A. P.
Published: October 2024

After a brief recount of small and large gauge transformations and the nature of observables, we discuss superselection sectors in gauge theories. There are an infinity of them, classified by large gauge transformations. Gauge theory sectors are labeled by the eigenvalues of a complete commuting set (CCS) of these transformations. In QED, the standard chemical potential is one such operator generating global U(1). There are many more given by the moments of the electric field on the sphere at infinity. In QCD, the CCS are constructed from the two commuting generators spanning a Cartan subalgebra. Large gauge transformations commute with the Hamiltonian and preserve the equations of motion. They form an infinite number of ‘classical symmetries’. But most of them are anamolous changing the superselection sectors. We show that any element of a large gauge transformation can be added to the standard Hamiltonian as a generalized chemical potential without changing field equations and that in QCD, they lead to confined and deconfined phases. A speculation about the physical meaning of these chemical potentials is also made.
Universal Composability Is Robust Compilation
Authors: Patrignani Marco , Künnemann Robert , Wahby Riad S. , Cecchetti Ethan
Published: October 2024

This article discusses the relationship between two frameworks: universal composability (

\(\mathsf{UC}\)

) and robust compilation (
RC
). In cryptography,

\(\mathsf{UC}\)

is a framework for the specification and analysis of cryptographic protocols with a strong compositionality guarantee:

\(\mathsf{UC}\)

protocols remain secure even when composed with other protocols. In programming language security,
RC
is a novel framework for determining secure compilation by proving whether compiled programs are as secure as their source-level counterparts no matter what target-level code they interact with. Presently, these disciplines are studied in isolation, though we argue that there is a deep connection between them and exploring this connection will benefit both research fields.

This article formally proves the connection between

\(\mathsf{UC}\)

and
RC
and then it explores the benefits of this connection (focussing on perfect, rather than computational

\(\mathsf{UC}\)

). For this, this article first identifies which conditions must programming languages fulfil in order to possibly attain

\(\mathsf{UC}\)

-like composition. Then, it proves

\(\mathsf{UC}\)

of both an existing and a new commitment protocol as a corollary of the related compilers attaining
RC
. Finally, it mechanises these proofs in DEEPSEC, obtaining symbolic guarantees that the protocol is indeed

\(\mathsf{UC}\)

.

Our connection lays the groundwork towards a better and deeper understanding of both

\(\mathsf{UC}\)

and
RC
, and the benefits we showcase from this connection provide evidence of scalable mechanised proofs for

\(\mathsf{UC}\)

.
Hydrothermal Signatures Discovered in Outcropping Rocks of the Los Humeros Geothermal Field (Mexico): A Geochemometric Exploration Case Study
Authors: Yáñez-Dávila D. , Santoyo E. , González-Partida E. , Pandarinath Kailasa , Santos-Raga G. , Mishra Sumit , Gómez-Salgado Z. G.
Published: October 2024

Hydrothermal geochemical signatures in outcropping rock samples of the super‐hot Los Humeros geothermal field were discovered by using an integrated geochemometric study of the mobility of components (major oxides) and trace elements. Chemical component and element mobilities were determined by using the Gresens–Grant equation for mass balances. A spatial distribution of component and element mobility patterns was carried out through the mineral characterization, hydrothermal alteration, and whole‐rock elemental analysis. Four alteration assemblages were mainly identified: (i) argillic–silicic; (ii) argillic–sericite; (iii) advance argillic–sulphate acid (alunite or jarosite); and (iv) silicic–carbonate. A clear increasing order of mobility for major oxides such as Fe2O3T, P2O5, K2O, MnO, SiO2, CaO, Al2O3, and MgO and trace elements such as Pb, Th, Sr, Zn, V, Rb, Cr, Cu, and Ba was inferred from hydrothermally altered rocks. The mobility of these components and trace elements showed a geochemical association with a higher contribution of Fe2O3T, CaO, V, Cu, Zn, and Sr and a lower contribution of K2O, Rb, Th, and Cr. The spatial distribution of hydrothermal signatures obtained by tracking the mobilities of major and trace elements in samples collected in a new sector of Los Humeros geothermal field is aligned with NW‐SE and NE‐SW fault systems. Three areas characterised by a higher permeability were identified, for the first time, from low‐cost analyses of rock samples by using energy‐dispersive X‐ray fluorescence spectrometry. The successful application results obtained from this study provided a new integrated geochemometric method to track high permeability zones for geothermal prospection tasks.
Development of MXene‐Enabled Titanium Carbide (TiC) Impurities‐Based Electrodes for the Fabrication and Circuit‐Level Testing of Gel‐Based Supercapacitors
Authors: Ahmad Muniba , Shuja Ahmed , Ali Muhammad , Sajid Fatima , Ashraf Saba
Published: October 2024

Flexible and stretchable supercapacitors developed on MXene‐enabled Titanium Carbide (TiC) impurities‐based electrodes with novel electrolytes are the point of focus in this work. Five different electrodes are prepared with different TiC content and symmetric supercapacitors are fabricated with three electrolytes named acrylamide, N,N′‐Dimethylacrylamide, and 2‐Hydroxyethyl methacrylate to achieve flexibility and improved energy storage. Before electrode fabrication, all the samples are tested with the X‐ray Diffraction technique. Cyclic voltammetry is performed at a potential window from −1 to 1 V to evaluate the specific capacitance of fabricated supercapacitors at multiple scan rates. Electrochemical impedance spectroscopy is performed to study the Randles circuit, and Rs values are calculated to examine the maximum physical area used for the evaluation of supercapacitors. Open‐circuit and short‐circuit tests are performed after charging the capacitor at 1 V for 2 min each time and compatibility of electrodes with different electrolytes is analyzed. The figures of merits for all the techniques used are discussed in detail. The highest values of the specific capacitances reported in our work are 50 and 79 F/g with novel electrolytes termed as N,N′‐Dimethylacrylamide and 2‐Hydroxyethyl methacrylate, respectively.
Stimulating Soluble Guanylyl Cyclase with the Clinical Agonist Riociguat Restrains the Development and Progression of Castration-Resistant Prostate Cancer
Authors: Zhang Ling , Troccoli Clara I. , Mateo-Victoriano Beatriz , Misiara Lincheta Laura , Jackson Erin , Shu Ping , Plastini Trisha , Tao Wensi , Kwon Deukwoo , Chen Xi Steven , Sharma Janaki , Jorda Merce , Kumar Surinder , Lombard David B. , Gulley James L. , Bilusic Marijo , Lockhart Albert C. , Beuve Annie , Rai Priyamvada
Published: October 2024

Castration-resistant prostate cancer (CRPC) is incurable and fatal, making prostate cancer the second leading cancer-related cause of death for American men. CRPC results from therapeutic resistance to standard-of-care androgen deprivation (AD) treatments, through incompletely understood molecular mechanisms, and lacks durable therapeutic options. In this study, we identified enhanced soluble guanylyl cyclase (sGC) signaling as a mechanism that restrains CRPC initiation and growth. Patients with aggressive, fatal CRPC exhibited significantly lower serum levels of the sGC catalytic product cyclic GMP (cGMP) compared with the castration-sensitive stage. In emergent castration-resistant cells isolated from castration-sensitive prostate cancer populations, the obligate sGC heterodimer was repressed via methylation of its β subunit. Genetically abrogating sGC complex formation in castration-sensitive prostate cancer cells promoted evasion of AD-induced senescence and concomitant castration-resistant tumor growth. In established castration-resistant cells, the sGC complex was present but in a reversibly oxidized and inactive state. Subjecting CRPC cells to AD regenerated the functional complex, and cotreatment with riociguat, an FDA-approved sGC agonist, evoked redox stress-induced apoptosis. Riociguat decreased castration-resistant tumor growth and increased apoptotic markers, with elevated cGMP levels correlating significantly with lower tumor burden. Riociguat treatment reorganized the tumor vasculature and eliminated hypoxic tumor niches, decreasing CD44+ tumor progenitor cells and increasing the radiosensitivity of castration-resistant tumors. Thus, this study showed that enhancing sGC activity can inhibit CRPC emergence and progression through tumor cell–intrinsic and extrinsic effects. Riociguat can be repurposed to overcome CRPC, with noninvasive monitoring of cGMP levels as a marker for on-target efficacy.

Significance: Soluble guanylyl cyclase signaling inhibits castration-resistant prostate cancer emergence and can be stimulated with FDA-approved riociguat to resensitize resistant tumors to androgen deprivation, providing a strategy to prevent and treat castration resistance.
Biomarkers of Nicotine and Toxicant Exposure by E-Liquid Nicotine Concentration Level among US Adult Exclusive E-Cigarette Users
Authors: Dai Hongying Daisy , Reyes Sara , Buckley James , Maloney Patrick
Published: October 2024

Background:

The current e-cigarette market has been rapidly evolving with an increase in the share of high nicotine concentration vaping products. This study examined urinary biomarkers of exposure (BOE) by nicotine concentration level among exclusive e-cigarette users.

Methods:

Data were drawn from wave 5 (December 2018–November 2019) of the Population Assessment of Tobacco and Health study. Between-subject differences in BOEs of nicotine, metal, tobacco-specific nitrosamine, and volatile organic compounds were examined across e-cigarettes containing nicotine or not [yes (n = 300) vs. no (n = 31) vs. non-tobacco use (n = 3,021)] and different nicotine concentration levels (0.1%–1.7%, 1.8%–4.9%, and 5.0%+).

Results:

Among 3,353 participants, exclusive e-cigarette users exhibited higher mean concentrations of nicotine metabolites than non-tobacco users. Nicotine e-cigarette users had higher concentrations of total nicotine equivalents-2 [TNE2; mean (95% confidence interval), 21.8 (15.2–31.2) vs. 0.2 (0.1–0.6) nmol/mg creatinine, P < 0.0001] and cotinine [1,418.2 (998.0–2,015.4) vs. 12.2 (0.1–0.6), P < 0.0001) ng/mg creatinine, P < 0.0001] than non-nicotine e-cigarette users. Users of e-cigarette products with nicotine levels of 1.8% to 4.9% had higher TNE2 and cotinine levels than those using 0.1% to 1.7%, though differences were insignificant after adjusting for covariates. As compared to non-tobacco users, nicotine vapers had higher concentrations of lead (adjusted P = 0.01).

Conclusions:

Nicotine containing e-cigarette users exhibited elevated levels of nicotine metabolites than non-nicotine containing vapers and non-tobacco users. Future research needs to investigate health effects of e-cigarette use across different nicotine levels.

Impact:

Regulating the nicotine content in e-cigarettes could be crucial in managing nicotine exposure and potentially mitigating associated health risks.
Figure S2 from Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network
Authors: Akturk Guray , Parra Edwin R. , Gjini Evisa , Lako Ana , Lee J. Jack , Neuberg Donna , Zhang Jiexin , Yao Shen , Laface Ilaria , Rogic Anita , Chen Pei-Hsuan , Sanchez-Espiridion Beatriz , Valle Diane M. Del , Moravec Radim , Kinders Robert , Hudgens Courtney , Wu Catherine , Wistuba Ignacio I. , Thurin Magdalena , Hewitt Stephen M. , Rodig Scott , Gnjatic Sacha , Tetzlaff Michael T.
Published: October 2024

Supplementary Figure 2
Supplementary Table 7 from Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia
Authors: Ding Yang-Yang , Kim Hannah , Madden Kellyn , Loftus Joseph P. , Chen Gregory M. , Allen David Hottman , Zhang Ruitao , Xu Jason , Chen Chia-Hui , Hu Yuxuan , Tasian Sarah K. , Tan Kai
Published: October 2024

Optimal Control Nodes (OCNs) identified using the OptiCon algorithm and Ph-like B-ALL specific gene regulatory network, and genes in the optimal control regions (OCRs) of each OCN.
Supplementary Table 2 from Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia
Authors: Ding Yang-Yang , Kim Hannah , Madden Kellyn , Loftus Joseph P. , Chen Gregory M. , Allen David Hottman , Zhang Ruitao , Xu Jason , Chen Chia-Hui , Hu Yuxuan , Tasian Sarah K. , Tan Kai
Published: October 2024

List of gene fusions identified and used in this study. Fusions were called using TARGET B-ALL datasets and the methods from He et al. (21). COG, Children's Oncology Group. USI, unique specimen identifier.
Supplementary Figure 6 from Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia
Authors: Ding Yang-Yang , Kim Hannah , Madden Kellyn , Loftus Joseph P. , Chen Gregory M. , Allen David Hottman , Zhang Ruitao , Xu Jason , Chen Chia-Hui , Hu Yuxuan , Tasian Sarah K. , Tan Kai
Published: October 2024

Weights of patient-derived leukemia xenografted mice remained stable during combination therapy. Mice weights (in grams, g) during treatment with TKI, venetoclax, or combination treatment were monitored as a proxy for drug toxicity and clinical status. Combination therapy did not result in more significant body weight loss (>20% of initial weight) as compared to vehicle or monotherapy in any of the six PDX models. N= 5 mice per treatment group. Each point represents mean +/- SD. The six leukemia PDX models correspond to those shown in Figure 5.
Supplementary Figure 1 from Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia
Authors: Ding Yang-Yang , Kim Hannah , Madden Kellyn , Loftus Joseph P. , Chen Gregory M. , Allen David Hottman , Zhang Ruitao , Xu Jason , Chen Chia-Hui , Hu Yuxuan , Tasian Sarah K. , Tan Kai
Published: October 2024

Gene expression of Ph-like cell lines recapitulates that of primary Ph-like ALL patient sample datasets. (A) Principal component analysis (PCA) of TARGET patient samples based on microarray gene expression show that their transcriptomes cluster separately by B-ALL subtype. Ph-like cell line gene expression by RNA-Seq (MUTZ5 and MHH-cALL-4 data from Cancer Cell Line Encyclopedia, TVA-1 data generated by authors) appropriately clusters with Ph+ and Ph-like B-ALL primary patient samples. (B) Expression of predicted OCN genes in Ph-like patient samples as compared to non-Ph-like favorable-risk B-ALL subtypes (defined here as ETV6-RUNX1, ERG-dysregulated, and hyperdiploid patient B-ALL samples).
Territoriality and Intellectual Property Infringement Proceedings
Authors: Tang Zheng (Sophia)
Published: October 2024

This article examines the principle of territoriality in intellectual property rights (IPR s) and its implications for cross-border infringement proceedings. It highlights the complexities arising from globalization and digital technologies, which challenge the traditional territorial nature of IPR s. The article compares jurisdictional approaches in the United States, the European Union, Korea, noting the strict adherence to territoriality in validity disputes and the varied stances on infringement claims. It also explores the innovative measures adopted by national courts, particularly in the context of Standard Essential Patents (SEP s), to extend their jurisdiction while respecting territorial limits. The article underscores China’s pragmatic approach, balancing respect for territoriality with judicial efficiency, and its proactive role in setting global FRAND terms for SEP s. The analysis suggests that while territoriality remains a fundamental principle, evolving judicial practices are adapting to the demands of a globalized economy.
Atypical Presentation and Postoperative Management of Vagal Nerve Tumors
Authors: Shing Samuel R. , Armache Maria , Llerena Pablo , O’Connor Mackenzie , Murphy Kira , Curry Joseph M. , Luginbuhl Adam J.
Published: October 2024

Objectives:

Tumors involving the vagus nerve are often clinically silent. We offer a case series with different clinical presentations and distinctive post-surgical sequelae that highlight some of the challenges associated with managing cervical vagal nerve tumors.

Methods:

Single-institution, retrospective review of patients with tumors involving the vagus nerve. We describe clinical presentations and postoperative sequelae of five patients who underwent surgical management of vagal nerve pathology with atypical presentation or subsequent clinical course.

Results:

Here, we present five patients treated at our institution for vagal tumors. In four of the five patients, the presenting symptoms resolved after surgery. Two patients presented with intractable neurogenic cough, and another two presented with autonomic symptoms, one with syncope/palpitations and the other with intractable sweating. The final patient presented with a rapidly enlarging vagal paraganglioma and developed intractable cough after resection. We present two patients with novel approach to vagal paragangliomas that underwent ligation of feeding blood supply without removing the tumor, resulting in resolution of an intractable cough in one patient and resolution of severe nighttime sweating in the other.

Conclusion:

Management of tumors associated with the cervical vagus nerve that present with symptoms or rapid growth poses a clinical dilemma. Consideration of the tumor origin with either enucleation of schwannomas or ligation of feeding vessels may preserve function while addressing the presenting symptoms.
Determinants of brain drain among physicians in Turkey: Findings from a national exploratory study
Authors: Bener Abdulbari , Ventriglio Antonio , Almas Furkan , Bhugra Dinesh
Published: October 2024

Background:

The shortage of physicians in Turkey is a highly critical emergency. In fact, physicians’ migration to developing or high-income countries, defined as brain drain, threatens the sustainability of the national healthcare system.

Aims:

This study explored the driving factors associated with Turkish Physicians’ brain drain, including high-economic inflation, social-politics, poor-living, equity, violence, and the desire to practice medical activity abroad.

Methods:

A cross-sectional survey of 1,861 Turkish physicians aged 25 to 65 years old was conducted employing the Brain Drain questionnaire, the Depression Anxiety Stress Scale (DASS-21), the Patient Health Questionnaire 9 (PHQ-9), and the Fatigue Assessment Scale (FAS).

Results:

Significant differences were observed among physicians staying in Turkey versus considering migration to Western countries, regarding their age, gender, marital status, educational level, occupational status, work years, hospital night shifts, income, and cigarette/nargileh smoking habits ( all p ⩽ .018). The main reasons for brain drain included transport problems, harassment, low salary, malpractice, bad environment, job insecurity, workload, burnout, treating difficult patients, inadequate postgraduate systems, peer-pressure, health safety concerns, and favoritism in the workplace, as well as stress and depression caused by work overload. In fact, depression, anxiety, stress, fatigue, and burnout varied significantly among the different groups of physicians (all p ⩽ .013). Additionally, key predictors of brain drain were better job opportunities, poor hospital management (in Turkey), job-related stress, dealing with difficult patients, research deficiencies, workload, burnout, transportation issues, short consultation time, low salary, and fatigue. Among the general factors contributing to the brain drain in the Turkish Health System, we identified significant issues related to research deficiencies, compulsory working duties, poor quality of postgraduate, inadequate medical-schools, poor hospital management, and shortage of consultants.

Conclusion:

Physicians’ migration is a major global public health concern, leading to substantial risks for healthcare services, especially in Turkey. Many physicians decide to migrate to work in Western countries.
Pre-disaster family visits and post-evacuation return to Fukushima among psychiatric inpatients evacuated to out-of-area hospitals after the nuclear accident
Authors: Suzuki Yuko , Terui Toshihiro , Kunii Yasuto , Kakamu Takeyasu , Hidaka Tomoo , Gotoh Daisuke , Anzai Nobuo , Niwa Shin-Ichi , Yabe Hirooki
Published: October 2024

Objective:

This study aimed to elucidate the effects of pre-evacuation family hospital visits on post-evacuation returns to Fukushima Prefecture (hometown) among psychiatric inpatients who mandatorily evacuated to hospitals outside the prefecture because of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident.

Method:

Of the inpatients in Fukushima, 44 were admitted to a hospital in the nearby Soso district on March 11, 2011, and were therefore included in the current analysis. We collected information on their discharge after the evacuation and family visits before the evacuation by reviewing the medical records of both the evacuation destination and former hospitals.

Results:

The average durations from the accident to post-evacuation return among patients with and those without former family visits were 681.8 days (standard error [SE] = 163.3) and 1,027.8 days (SE = 152.0), respectively. The log-rank test showed a tendency of earlier return to Fukushima among inpatients who had received family visits to the hospital before evacuation ( p = .073).

Conclusions:

The results highlight the critical need for close collaboration between psychiatric medical practitioners and families, to not only support patients’ community reintegration into daily life but also facilitate a timely return to their hometowns following long-distance evacuation caused by an unforeseen large-scale disaster.