bluuebunny/crossref_metadata_2025 huggingface dataset:
Strengthening Trade Relations between Pakistan and Afghanistan: Opportunities and Challenges
Authors: Khan Muhammad Zubair
Published: November 2024

This paper delves into the complex dynamics of trade relations between Pakistan and Afghanistan, two countries with shared cultural heritage and geographic proximity. Despite these inherent advantages, bilateral trade volumes have remained notably low, hindered by historical, geopolitical, and economic factors. Utilizing a mixed-methods approach including secondary data analysis and interviews with stakeholders, the research identifies and analyzes key obstacles impeding optimal trade relations. The analysis reveals several challenges, including the stalled negotiations on the Preferential Trade Agreement (PTA), non-tariff barriers, and issues in transit trade operations. Afghanistan's ban on Pakistani meat imports, non-tariff barriers on pharmaceutical products, and imposition of export taxes on coal are among the hurdles examined. Furthermore, Pakistan's unilateral measures to enhance trade, such as the Barter Trade Mechanism, are scrutinized alongside issues in transit trade operations, including delays, smuggling, and bureaucratic inefficiencies. The study emphasizes the need for both countries to adopt a cooperative approach, address mutual concerns, and streamline trade procedures to unlock the untapped potential of their economic partnership. Short-to-medium-term recommendations include finalizing the APTTA, improving border crossing points, and enhancing customs cooperation. In the medium-to-long term, the paper suggests pursuing regional transit trade agreements, investing in infrastructure projects like the Trans Afghan Railway, and advancing multilateral connectivity initiatives. Ultimately, the paper underscores the significance of economic cooperation between Pakistan and Afghanistan in fostering regional stability and prosperity. By addressing the identified challenges and implementing the recommended measures, both countries can bolster their trade relations, unlock economic opportunities, and contribute to broader regional connectivity and development goals.
Critical Analysis on Existing Framework of ADR in Pakistan
Authors: Khan Bilal , Iqbal Javed
Published: November 2024

The mechanism of resolving issues quasi-judicially has turned out to be an effective means especially in jurisdictions where backlogs are hiking. However, the current framework in Pakistan addressing Alternate Dispute Resolution faces certain shortcomings and challenges which calls in question its fairness, accessibility, and effectiveness. The paper provides a background of ADR in Pakistan, outlining the history, development, and types of ADR mechanisms used. It then delves into an in-depth analysis of the existing ADR framework, discussing the laws, regulations, and roles of various bodies involved. Through this analysis, discrepancies and weaknesses in the framework are identified, with a focus on transparency, accessibility, efficiency, and effectiveness. The impact of these discrepancies on the overall ADR system is examined, including their effects on access to justice, fairness, and public trust. Based on the findings, this paper provides recommendations for addressing the identified discrepancies, proposing policy changes, legislative reforms, and initiatives that can improve the effectiveness and fairness of ADR in Pakistan. By highlighting the discrepancies and providing recommendations for improvement, this research paper aims to contribute to the ongoing discussions regarding the enhancement of the ADR framework in Pakistan for more efficient and equitable dispute resolution. ADR Act of 2017 is the focal point of our research as an overwhelming majority of ADR Practice in Pakistan revolves around it including accreditation and notification of mediators and mediation practices.
Historical Aspects in the Geological Investigation of Northern Greenland.
Authors: Dawes Peter R. , Haller John
Published: November 2024

Certain geological maps and photographs, prepared for publication by the late Dr. LAUGE KOCH, are presented here together with an explanatory text. The material stems from the first expeditions that carried out systematic topographical and geological mapping in northern Greenland, viz. the 2nd Thule Expedition 1916-18 and the Bicentenary Jubilee Expedition 1920-23. The latter expedition traversed the entire coast from Melville Bugt around the northern tip of Greenland and into eastern Peary Land. Regrettably the geological results of this expedition were never published in full. Geological map coverage of northern Greenland was planned by KOCH as a series of coloured map sheets to be issued with descriptive texts in Meddelelser om Grønland. Only two, of a series of five, actually were published, in 1929 and 1933; the three outstanding maps, originally in proof print in 1931, are presented here.Several annotated photographs that were to have appeared as figures to illustrate the descriptive texts, are also reproduced.The main significance of the maps and photographs is that they define for the first time the regional outcrop pattern of some of the rock units that became part of the established stratigraphical column of northern Greenland. Of particular importance is the illustration of the Silurian geology and a definition of which rock sequences were actually referred to a given formation. The maps and photographs are valuable reference material and they are essential for a full appraisal of the early ideas about the Silurian geology, as well as in any subdivision and eventual redefinition of the existing Silurian formations.
Geological Map of Northeast Greenland 75°-82° N. Lat.
Authors: Haller John
Published: November 2024

The "Geological Map of Northeast Greenland" was compiled and drafted in 1964, and reached the stage of proof-print in 1968. It was planned as part of a twosheet series of geologic maps on a scale of 1: 1,000,000 that was to summarize the results of the Danish East Greenland Expeditions 1926 to 1958, conducted by LAUGE KOCH. The present map sheet covers the region from latitudes 75° to 82°N. The geological information contained in this map is based on reports published before 1964 (see list of references) and on field observations and reconnaissance flights the author had made in the summers of 1955, 1956, and 1958. In view of more recentand systematic field investigations by the Geological Survey of Greenland in the region north of latitude 80°, the present map has become more of a historical document recording the state-of-the-art as of 1960. For the region south of latitude 79°N, however, the m,ap still is the most recent version.
Demographic studies in two villages in the Upernavik District.
Authors: Balslev Jørgensen J. , Hansen Keld , Østergaard Hansen A.
Published: November 2024

The present work was carried out as part of a major investigation into Human Adaptation under the IBP, International Biological Program. Other results of these investigations have been published in Meddelelser om Grønland (Volumes no. 202 .2,203.1, 203 .2). Statens Lægevidenskabelige Forskningsråd (L 78/68 and 512-33/69) andMinisteriet for Grønland have provided the necessary economical support.
Notes in occurrence and distribution of Lichens in South East Greenland.
Authors: Steen Hansen Eric
Published: November 2024

The present investigation of occurrence and distribution of lichens in South East Greenland is based on a study of 6.000 collections of 155 species of macro- and microlichens collected by the author in 1970 and 1971 in 28 localities situated between Hermods Vig in the Skjoldungen area, c. 63° !at. N., and Mudderbugt in the Kangerdlugssuaq area, c. 68° !at. N. Five of the species, viz. Caloplaca marina (WEDD.) ZAHLBR., Coriscium viride (ACH.) VAIN., Ochrolechia grimmiae LYNGE, Parmeliopsis hyperopta (ACH.) ARN. and Toninia coeruleonigricans (LIGHTF.) TH. FR., are new additions to the lichen flora of East Greenland. Previous lichenological research work in South East Greenland is surveyed in an introductory chapter. The collected species of lichens are grouped on the basis of their ecological preferences, and an account is given of some characteristic features of the lichen vegetation at the investigated localities within the Skjoldungen-, the Angmagssalikand the Kangerdlugssuaq area. Distribution maps of four species, viz. Cladonia cyanipes (SOMM.) NYL., Lecanora straminea (WAHLENB.) AcH., Parmeliopsis ambigua (WuLF.) NYL. and Peltigera venosa (L.) BAUMG., have been compiled.
Ornithological and ecological studies in S. W. Greenland (59°46'-62°27' N. Lat.)
Authors: Salomonsen Finn
Published: November 2024

This work is the first in a series of papers describing the ecology of birds in Western Greenland, particularly the sea-birds. In this paper the situation in S. W. Greenland has been described, including the districts of Nanortalik, Julianehab, Narssaq and Frederikshab. In the former three districts, which constitute the southernmost part of West Greenland, the East Greenland ice ("Storis") virtually prevents the formation of actual sea-bird colonies. On the other hand, the southern position of this area has given rise to the development of a more mitigated climate in the interior country and this has caused the formation of a subarctic zone, being part of the boreal, not the arctic biome. The climate, the plan-cover and other particulars of the subarctic zone are described, including the human trades in this zone as consequences of the climate. A detailed account of the immigration of six subarctic bird-species to Greenland is given as well as notes on their distribution and life-habits in Greenland. In Frederikshab District a number of sea-bird colonies have been developed, some of which are rather large. The natural history of these colonies are described in detail, and a methodical analysis is given of the factors governing their development, as well as the significant botanical consequences of the presence of avian guano, important even for the human population. Some new designations for various conceptions have been proposed, necessary for the discussion of these matters which have not previously been seriously studied. A description of each sea-bird colony in Frederikshåb District is followed by notes on the sea-bird migration and on localbird-names in the district and, finally, by a discussion on the transglacial migration.
R-matrix theory based calculation of elastic cross-sections of gas molecules and analysis of its correlation with insulation strength
Authors: Zhang Xing-Yi , Yang Shuai , Shang Shu-Xiang , Wu Shao-Bo , Wang Hang , Xiao Ji-Xiong ,   Hubei Engineering Research Center for Safety Monitoring of New Energy and Power Grid Equipment, Hubei University of Technology, Wuhan 430068, China
Published: November 2024

The elastic collision cross-section is a key parameter in the study of inter-particle interactions, and it helps to reveal the microscopic mechanism of gas insulation. For this reason, based on the  R -matrix theory, the elastic collision cross-sections of 24 gas molecules at 0–15 eV are calculated , and cross-section characteristic parameters of the lowest resonance state energy and its peak are extracted. Then the calculated and experimental values of SF6, CF2Cl2, and i-C3F7CN cross-sections are compared, and the low-energy cross-section data of i-C3F7CN at 0–1 eV are given. Furthermore the effects of Cl-substitution and carbon chain length on the cross-section parameters are analysed. Finally the correlation between cross-section characteristic parameters and insulation strength is investigated. The results show that the lowest shape resonance state energy for each molecule is in better agreement with the existing data within a mean square error of 0.181. For the F-substitution, the resonance energy gradually increases but the peak value gradually decreases, which the carbon chain extension is the opposite to: the resonance state energy gradually decreases but the peak value gradually increases. The lowest resonance energy and peak value are strongly related to the insulation strength. The lower its lowest resonance energy and the larger the corresponding peak value, the higher the molecular insulation strength is. The relevant data can theoretically supplement existing experimental data. This study provides low energy cross-section properties of various insulating gas molecules, which can be useful for qualitatively evaluating the insulating properties of gas molecules and quickly screening SF6 alternative gases.
Passive accumulation of alkaloids in inconspicuously colored frogs refines the evolutionary paradigm of acquired chemical defenses
Authors: Tarvin Rebecca D , Coleman Jeffrey L , Donoso David A , Betancourth-Cundar Mileidy , López-Hervas Karem , Gleason Kimberly S , Sanders J Ryan , Smith Jacqueline M , Ron Santiago R , Santos Juan C , Sedio Brian E , Cannatella David C , Fitch Richard
Published: November 2024

Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended. As a result, our understanding of how chemical defense evolved in this group is incomplete. Here we provide new data showing that, in contrast to previous studies, species from each undefended poison frog clade have measurable yet low amounts of alkaloids. We confirm that undefended dendrobatids regularly consume mites and ants, which are known sources of alkaloids. Thus, our data suggest that diet is insufficient to explain the defended phenotype. Our data support the existence of a phenotypic intermediate between toxin consumption and sequestration — passive accumulation — that differs from sequestration in that it involves no derived forms of transport and storage mechanisms yet results in low levels of toxin accumulation. We discuss the concept of passive accumulation and its potential role in the origin of chemical defenses in poison frogs and other toxin-sequestering organisms. In light of ideas from pharmacokinetics we incorporate new and old data from poison frogs into an evolutionary model that could help explain the origins of acquired chemical defenses in animals and provide insight into the molecular processes that govern the fate of ingested toxins.
Lacticaseibacillus rhamnosus P118 enhances host tolerance to Salmonella infection by promoting microbe-derived indole metabolites
Authors: Wang Baikui , Peng Xianqi , Zhou Xiao , Siddique Abubakar , Yao Jiayun , Zhang Haiqi , Li Weifen , Li Yan , Yue Min
Published: November 2024

Salmonella
is one of the most common foodborne pathogens, resulting in inflammatory gastroenteritis and frequently accompanied by dysbiosis. Gut commensals, such as
Lactobacillus
species, have been proven to exhibit broad anti-bacterial activities and protect hosts against pathogenic infections. Here,
Lacticaseibacillus rhamnosus
strain P118, with great probiotic properties, was screened from 290 isolates recovered from fermented yoghurts and piglet intestines using traditional and
C. elegans
-infection screening strategies. Notably, P118 and its supernatant exhibited great antibacterial activities and attenuated
C. elegans
susceptibility to
Salmonella
infection. We found that P118 protected mice against
Salmonella
lethal infections by enhancing colonization resistance, reducing pathogen invasion, alleviating intestinal pro-inflammatory response, and improving microbial dysbiosis and metabolic disorders. Microbiota and fecal metabolome analyses suggested P118 administration significantly decreased the relative abundances of harmful microbes (e.g.,
Salmonella
,
Anaeroplasma
,
Klebsiella
) and increased the fecal levels of tryptophan and its derivatives (indole, indole-3-acrylic acid, 5-hydroxytryptophan, 5-methoxyindoleacetate). Deterministic processes determined the gut microbial community assembly of P118-pretreated mice. Integrated omics further demonstrated that P118 probiotic activities in enhancing host tolerance to
Salmonella
infection were mediated by microbe-derived tryptophan/indole metabolites (e.g., indole-3-acrylic acid, indole, tryptophan, 5-methoxyindoleacetic acid, and 5-hydroxytryptophan). Collective results demonstrate that
L. rhamnosus
P118 could enhance host tolerance to
Salmonella
infections via various pathways, including direct antibacterial actions, inhibiting
Salmonella
colonization and invasion, attenuating pro-inflammatory responses of intestinal macrophages, and modulating gut microbiota mediated by microbe-derived indole metabolites.
Estimating bone marrow adiposity from head MRI and identifying its genetic architecture
Authors: Kaufmann Tobias , Bjørnstad Pål Marius , Falck Martin , Nerland Stener , O’Connell Kevin , Frei Oleksandr , Andreassen Ole A , Westlye Lars T , Djurovic Srdjan , Hughes Timothy
Published: November 2024

Bone marrow adiposity changes radically through the lifespan, but this phenomenon is poorly characterised and understood in humans. Large datasets of magnetic resonance imaging (MRI) scans of the head have been collected to study the human brain, but also contain unexploited information about other organs. We developed an artificial neural network that localises calvarial bone marrow in T1-weighted MRI head scans, enabling us to study its composition in several large MRI datasets, and to model sex-dimorphic age trajectories, including the effect of menopause. We revealed high heritability in single-nucleotide polymorphism and twin data, and identified 41 genetic loci significantly associated with the trait, including six sex-specific loci. Integrating mapped genes with existing bone marrow single-cell RNA-sequencing data revealed patterns of adipogenic lineage differentiation and lipid loading. Finally, we identified significant genetic correlations with several human traits, including cognitive ability and Parkinson’s disease, which is intriguing in light of the recently discovered channels that link calvarial bone marrow to the meninges.
Information, certainty, and learning
Authors: Harris Justin A , Gallistel CR
Published: November 2024

More than four decades ago, Gibbon and Balsam (1981) showed that the acquisition of Pavlovian conditioning in pigeons is directly related to the informativeness of the conditioning stimulus (CS) about the unconditioned stimulus (US), where informativeness is defined as the ratio of the US-US interval (
C
) to the CS-US interval (
T
). However, the evidence for this relationship in other species has been equivocal. Here, we describe an experiment that measured the acquisition of appetitive Pavlovian conditioning in 14 groups of rats trained with different
C
/
T
ratios (ranging from 1.5 to 300) to establish how learning is related to informativeness. We show that the number of trials required for rats to start responding to the CS is determined by the
C
/
T
ratio and, remarkably, the specific scalar relationship between the rate of learning and informativeness aligns very closely to that previously obtained with pigeons. We also found that the response rate after extended conditioning is strongly related to
T
, with the terminal CS response rate being a scalar function of the CS reinforcement rate (1/
T
). Moreover, this same scalar relationship extended to the rats’ response rates during the (never-reinforced) inter-trial interval, which was directly proportional to the contextual rate of reinforcement (1/
C
). The findings establish that animals encode rates of reinforcement, and that conditioning is directly related to how much information the CS provides about the US. The consistency of the data across species, captured by a simple regression function, suggests a universal model of conditioning.
Paracrine rescue of MYR1-deficient Toxoplasma gondii mutants reveals limitations of pooled in vivo CRISPR screens
Authors: Torelli Francesca , M da Fonseca Diogo , Butterworth Simon , Young Joanna C , Treeck Moritz
Published: November 2024

Toxoplasma gondii
is an intracellular parasite that subverts host cell functions via secreted virulence factors. Up to 70% of parasite-controlled changes in the host transcriptome rely on the MYR1 protein, which is required for the translocation of secreted proteins into the host cell. Mice infected with MYR1 knock-out (KO) strains survive infection, supporting a paramount function of MYR1-dependent secreted proteins in
Toxoplasma
virulence and proliferation. However, we have previously shown that MYR1 mutants have no growth defect in pooled
in vivo
CRISPR-Cas9 screens in mice, suggesting that the presence of parasites that are wild-type at the
myr1
locus in pooled screens can rescue the phenotype. Here, we demonstrate that MYR1 is not required for the survival in IFN-γ-activated murine macrophages, and that parasites lacking MYR1 are able to expand during the onset of infection. While ΔMYR1 parasites have restricted growth in single-strain murine infections, we show that the phenotype is rescued by co-infection with wild-type (WT) parasites
in vivo,
independent of host functional adaptive immunity or key pro-inflammatory cytokines. These data show that the major function of MYR1-dependent secreted proteins is not to protect the parasite from clearance within infected cells. Instead, MYR-dependent proteins generate a permissive niche in a paracrine manner, which rescues ΔMYR1 parasites within a pool of CRISPR mutants in mice. Our results highlight an important limitation of otherwise powerful
in vivo
CRISPR screens and point towards key functions for MYR1-dependent
Toxoplasma
-host interactions beyond the infected cell.
Measuring changes in Plasmodium falciparum census population size in response to sequential malaria control interventions
Authors: Tiedje Kathryn E , Zhan Qi , Ruybal-Pésantez Shazia , Tonkin-Hill Gerry , He Qixin , Tan Mun Hua , Argyropoulos Dionne C , Deed Samantha L , Ghansah Anita , Bangre Oscar , Oduro Abraham R , Koram Kwadwo A , Pascual Mercedes , Day Karen P
Published: November 2024

Here we introduce a new endpoint “census population size” to evaluate the epidemiology and control of
Plasmodium falciparum
infections, where the parasite, rather than the infected human host, is the unit of measurement. To calculate census population size, we rely on a definition of parasite variation known as multiplicity of infection (MOI

var

), based on the hyper-diversity of the
var
multigene family. We present a Bayesian approach to estimate MOI

var

from sequencing and counting the number of unique DBLα tags (or DBLα types) of
var
genes, and derive from it census population size by summation of MOI

var

in the human population. We track changes in this parasite population size and structure through sequential malaria interventions by indoor residual spraying (IRS) and seasonal malaria chemoprevention (SMC) from 2012 to 2017 in an area of high-seasonal malaria transmission in northern Ghana. Following IRS, which reduced transmission intensity by > 90% and decreased parasite prevalence by ∼40-50%, significant reductions in
var
diversity, MOI

var

, and population size were observed in ∼2,000 humans across all ages. These changes, consistent with the loss of diverse parasite genomes, were short lived and 32-months after IRS was discontinued and SMC was introduced,
var
diversity and population size rebounded in all age groups except for the younger children (1-5 years) targeted by SMC. Despite major perturbations from IRS and SMC interventions, the parasite population remained very large and retained the
var
population genetic characteristics of a high-transmission system (high
var
diversity; low
var
repertoire similarity) demonstrating the resilience of
P. falciparum
to short-term interventions in high-burden countries of sub-Saharan Africa.
Distinct T Cell Receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus
Authors: Rowell Jasmine , Lau Ching-In , Ross Susan , Yanez Diana C , Peña Oscar A , Chain Benny , Crompton Tessa
Published: November 2024

Here we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8-single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3’TRAV and 5’TRAJ rearrangements in all populations, whereas adult repertoires used more 5’TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3’TRAV and 5’TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire.The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.
Macro-scale patterns in functional connectivity associated with ongoing thought patterns and dispositional traits
Authors: Hardikar Samyogita , Mckeown Bronte , Schaare H Lina , Wallace Raven Star , Xu Ting , Lauckener Mark Edgar , Valk Sofie Louise , Margulies Daniel S , Turnbull Adam , Bernhardt Boris C , Vos de Wael Reinder , Villringer Arno , Smallwood Jonathan
Published: November 2024

Complex macro-scale patterns of brain activity that emerge during periods of wakeful rest provide insight into the organisation of neural function, how these differentiate individuals based on their traits, and the neural basis of different types of self-generated thoughts. Although brain activity during wakeful rest is valuable for understanding important features of human cognition, its unconstrained nature makes it difficult to disentangle neural features related to personality traits from those related to the thoughts occurring at rest. Our study builds on recent perspectives from work on ongoing conscious thought that highlight the interactions between three brain networks – ventral and dorsal attention networks, as well as the default mode network. We combined measures of personality with state-of-the-art indices of ongoing thoughts at rest and brain imaging analysis and explored whether this ‘tri-partite’ view can provide a framework within which to understand the contribution of states and traits to observed patterns of neural activity at rest. To capture macro-scale relationships between different brain systems, we calculated cortical gradients to describe brain organisation in a low-dimensional space. Our analysis established that for more introverted individuals, regions of the ventral attention network were functionally more aligned to regions of the somatomotor system and the default mode network. At the same time, a pattern of detailed self-generated thought was associated with a decoupling of regions of dorsal attention from regions in the default mode network. Our study, therefore, establishes that interactions between attention systems and the default mode network are important influences on ongoing thought at rest and highlights the value of integrating contemporary perspectives on conscious experience when understanding patterns of brain activity at rest.
Differences in HIV-1 reservoir size, landscape characteristics and decay dynamics in acute and chronic treated HIV-1 Clade C infection
Authors: Reddy Kavidha , Lee Guinevere Q , Reddy Nicole , Chikowore Tatenda JB , Baisley Kathy , Dong Krista L , Walker Bruce D , Yu Xu G , Lichterfeld Mathias , Ndung’u Thumbi
Published: November 2024

Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are the main barrier to cure efforts. Antiretroviral therapy (ART) intensification by early initiation has been shown to enable post-treatment viral control in some cases but the underlying mechanisms are not fully understood. We hypothesized that ART initiated during the hyperacute phase of infection before peak will affect the size, decay dynamics and landscape characteristics of HIV-1 subtype C viral reservoirs.We studied 35 women at high risk of infection from Durban, South Africa identified with hyperacute HIV infection by twice weekly testing for plasma HIV-1 RNA. Study participants included 11 who started ART at a median of 456 (297-1203) days post onset of viremia (DPOV), and 24 who started ART at a median of 1 (1-3) DPOV. We used peripheral blood mononuclear cells (PBMC) to measure total HIV-1 DNA by ddPCR and to sequence reservoir viral genomes by full length individual proviral sequencing (FLIP-seq) from onset of detection of HIV up to 1 year post treatment initiation.Whereas ART in hyperacute infection blunted peak viremia compared to untreated individuals (p<0.0001), there was no difference in total HIV-1 DNA measured contemporaneously (p=0.104). There was a steady decline of total HIV DNA in early treated persons over 1 year of ART (p=0.0004), with no significant change observed in the late treated group. Total HIV-1 DNA after one year of treatment was lower in the early treated compared to the late treated group (p=0.02). Generation of 697 single viral genome sequences revealed a difference in the longitudinal proviral genetic landscape over one year between untreated, late treated, and early treated infection: the relative contribution of intact genomes to the total pool of HIV-1 DNA after 1 year was higher in untreated infection (31%) compared to late treated (14%) and early treated infection (0%). Treatment initiated in both late and early infection resulted in a more rapid decay of intact (13% and 51% per month) versus defective (2% and 35% per month) viral genomes. However, intact genomes were still observed one year post chronic treatment initiation in contrast to early treatment where intact genomes were no longer detectable. Moreover, early ART reduced phylogenetic diversity of intact genomes and limited the seeding and persistence of cytotoxic T lymphocyte immune escape variants in the reservoir.Overall, our results show that whereas ART initiated in hyperacute HIV-1 subtype C infection did not impact reservoir seeding, it was nevertheless associated with more rapid decay of intact viral genomes, decreased genetic complexity and immune escape in reservoirs, which could accelerate reservoir clearance when combined with other interventional strategies.
Identification of Suitable Target/E3 Ligase Pairs for PROTAC Development using a Rapamycin-induced Proximity Assay (RiPA)
Authors: Adhikari Bikash , Schneider Katharina , Diebold Mathias , Sotriffer Christoph , Wolf Elmar
Published: November 2024

The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest. As more and more ligands for novel E3 ligases are discovered, the chemical effort to identify the best E3 ligase for a given target is exploding. Therefore, a genetic system to identify degradation-causing E3 ligases and suitable target/E3 ligase pairs is urgently needed. Here we used the well-established dimerization of the FKBP12 protein and FRB domain by rapamycin to bring the target protein WDR5 into proximity with candidate E3 ligases. Strikingly, this rapamycin-induced proximity assay (RiPA) revealed that VHL, but not Cereblon, is able to induce WDR5 degradation - a finding previously made by PROTACs, demonstrating its predictive power. By optimizing the steric arrangement of all components and fusing the target protein with a minimal luciferase, RiPA can identify the ideal E3 for any target protein of interest in living cells, significantly reducing and focusing the chemical effort in the early stages of PROTAC development.
Lifestyles and their relative contribution to biological aging across multiple organ systems: change analysis from the China Multi-Ethnic Cohort Study
Authors: Zhang Yuan , Tang Dan , Zhang Ning , Xiang Yi , Hu Yifan , Qian Wen , Baima Yangji , Ding Xianbin , Wang Ziyun , Yin Jianzhong , Xiao Xiong , Zhao Xing
Published: November 2024

Biological aging exhibits heterogeneity across multi organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China.To examine the associations of healthy lifestyle with comprehensive and organ-specific biological ages and which lifestyle factors contribute most.This study involved 8,396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) Study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera-Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation.About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in healthy lifestyle index showed a protective association with the acceleration of all biological ages, with a mean shift of –0.19 (95%CI: –0.34, –0.03) in the comprehensive biological age acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively.Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Optimal tuning of multi-PID controller using improved CMOCSO algorithm
Authors: Hu Ying , Liu Xiongyan , Chen Hao
Published: November 2024

To mitigate synchronization errors within a multi-PID controller system and enhance its resistance to interference, an improved competitive and cooperative swarm optimizer for constrained multi-objective optimization (CMOCSO) algorithm is employed to optimize the parameters of the multi-PID controller. Initially, a mathematical model representing the constrained multi-objective problem associated with the multi-PID controller is formulated. In this model, the parameters are designated as decision variables, the performance index serves as the objective function, and the stability constraints of the system are incorporated. Subsequently, an improved CMOCSO algorithm is introduced, which bifurcates the evolutionary process into two distinct stages using a central point-moving strategy; each stage employs different evolutionary techniques to accelerate convergence rates, and a novel grouping strategy is implemented to increase the learning efficiency of the population. The efficacy of the algorithm is evaluated through testing on 16 standard functions, demonstrating its effectiveness in addressing constrained multi-objective problems. Ultimately, the algorithm is applied to optimize the parameters of the multi-PID controller. The simulation results indicate that the proposed method yields superior control performance, reduced synchronization errors, and notable interference resistance capacity.
The role of andrographolide as a potential anticancer agent against gastric cancer cell lines: a systematic review
Authors: Anis Amiera Muhamad Alojid , Tuan Kub Tuan Noorkorina , Harun Azian , Mohamud Rohimah , Razian Nur Rina Alissa , Muhammad Ismadi Yasmin Khairani , Wan Alias Wan Alif Syazwani , Abdulrazak Mohammed Hussain , Teni Ernawati
Published: November 2024

Objective

To critically analyse literature on the anticancer properties of andrographolide in in vitro studies on gastric cancer cells.

Method

This study systematically reviewed articles from 2013 to 2024 across five prominent databases; PubMed, Google Scholar, Web of Science, Scopus, and Science Direct, EMBASE, Cochrane library and DOAJ. The study eligibility criteria include original studies assessing using gastric cancer cell lines and articles utilizing extracted andrographolide from Andrographis paniculata or standard andrographolide source treatment. The following exclusion criteria were articles written in a different language, review articles, book chapters, conference articles, scientific reports. Duplicated articles were removed using Mendeley software.

Result

Out of 93 articles, six were relevant, primarily focusing on in vitro analyses with gastric adenocarcinoma cell lines.

Conclusion

These studies indicate that andrographolide can hinder the cell cycle, suppress cell proliferation, alleviate oxidative stress, and induce apoptosis by prompting gastric cancer cells to undergo self-destruction, which is a crucial mechanism for controlling and eliminating cancerous growths.
Optimizing Emergency Response: Strategies Studies for Enhancing Hospital Management for Traffic Accident Victims
Authors: Purwoto Ady , Rachmani Enny , Isworo Slamet
Published: November 2024

Background and Objectives: Traffic accidents are a major issue in Indonesia, requiring urgent attention, especially in terms of response time and accuracy in emergency care. With the high frequency of accidents each year, hospitals need to be equipped to provide prompt, high-quality treatment. This study aims to examine hospital management strategies in improving emergency response for traffic accident victims using a mixed-methods approach. 
Methods: A systematic search was conducted across databases like Medline, PubMed, and Google Scholar using keywords such as 'Emergency Response Time, System Administration Complexity, Human Resource Limitations, and Inter-Unit Coordination. Seventeen relevant articles were identified.
Results: The study found that the average emergency response time was 7.3 minutes, exceeding the ideal 5-minute standard. Major factors contributing to delays included administrative system complexity (43%), human resource limitations (27%), and poor inter-unit coordination (30%). Challenges such as incomplete integration of the hospital information management system, high workload, especially during night shifts, and limited trauma-specific facilities were also identified. While triage processes met standards, bottlenecks in administration and support unit coordination caused delays. Emergency department staff demonstrated good competency (8.2/10), but the high nurse-to-patient ratio (1:8) impacted service quality. The survival rate for moderate to severe trauma cases was 89%, with better outcomes for patients treated within the golden hour.
Conclusion: Traffic accidents remain a critical concern in Indonesia, requiring improved emergency response systems. Hospitals must address issues in human resources, equipment, and coordination to enhance the speed and quality of emergency care, ultimately improving patient survival outcomes.
Type 1 Diabetes (T1D) in Children under 5 Years of Age: Multicentric Study of 22 Cases
Authors: Boiro Djibril , Mbaye Aminata , Sow Amadou , Niang Babacar , Ndongo Aliou Abdoulaye , Fall Fatou Adama , Seck Ndiogou , Basse Idrissa , Sow Ndeye Fatou , Gueye Modou
Published: November 2024

Introduction: The incidence of T1D is increasing worldwide, particularly in young children under 6 years of age. The objective of this study was to describe the characteristics of type 1 diabetes in children under 5 years of age in our resource-limited country setting.
Materials and Methods: This was a retrospective, descriptive study over a period from January 2018 to July 2022 in Dakar. All type 1 diabetic children under 5 years of age were included except those with an unusable file or less than 6 months of follow-up.
Results: We collected 22 records of children aged 0 to 5 years, with a prevalence of 7.8% of all children followed in the two centers. The socioeconomic level was considered average for 54% of patients. Ketoacidosis was the main mode of discovery in our patients (86%). The nutritional status was good for 77% of the children followed and 5% were overweight. The average HbA1c was 10.57 ± 0.5%. Analog insulins were the main insulins used by our patients, (64%). The average daily dose of insulin was 1.08 IU /kg. The diet was normal in the majority of patients (90%). No patient had a chronic complication during follow-up. Severe hypoglycemia was noted in 20% of cases. All our patients benefited from daily glycemic monitoring and had a notebook available. The monitoring rate was 3 checks, i.e. one check before each meal. No deaths were reported.
Conclusion: Diabetes in children under 5 years of age is not common. The majority of children are on insulin analogues with a glycemic control far from optimal. A prospective study could allow us to better identify the problems in order to provide appropriate solutions.
An Extremely Rare Case of Cardiac Hydatid Cyst Co-infected with Brevundimonas Nasdae: Diagnostic Challenges and Management
Authors: KADDARI Fatimazahrae , ELMASRIOUI Joumana , ARAFAOU Dicko , THIOMBIANO Abdoulaziz , MHIRIG Ibtissam , BOUCHTELLA Yassine , MARDOULI Mouhcine EL , SORAA Nabila , HOUATI Rachid EL , ELKARIMI Saloua , ELHATTAOUI Mustapha
Published: November 2024

Cardiac hydatid cyst (HC) is a rare localisation of hydatidosis. The main preoperative diagnostic tools are serology, Transthoracic Echocardiography (TTE), Cardiac Tomography (CT) and Nuclear Magnetic Resonance Imaging (MRI). MRI is the key examination for diagnosing cardiac masses. It enables anatomical relationships to be studied and a reliable etiological orientation to be made. We report a challenging case of pericardial hydatid cyst associated to a rare infection to Brevundimonas nasdae clinically revealed by chronic dyspnea and atypical acute chest pain evolving in a febrile context. In our case, the HC presented as a cardiac mass, with an atypical appearance on echocardiography suggestive of a rhabdomyosarcoma.  The MRI rectified the diagnosis, which was subsequently confirmed on operative finding, and on anatomo-pathological examination. The Patient was successfully managed after multidisciplinary treatment including combined surgical, antibiotics and antiparasitic treatments.
Green synthesis of metal oxide nanoparticles using plant extract, its structural and optical properties and application
Authors: Jan Shantul , Kasi Jafar Khan , Bilal Ahmed
Published: November 2024

The nanoparticles being the most utilized invention of nanoscience and technology, which is used in many aspects of science and medicine. These remarkable utilization of particles is due to their diverse properties at nano level. The chemical and physical approach to formation of nanoparticles are toxic to surroundings also leading to less efficient usage of them in medical perspective. In this article green synthesis of cobalt ferrite nanoparticles is done by sol-gel auto combustion using Caralluma Tuberculata extract as reducing agent, iron nitrate and cobalt nitrate as precursor salts. Cobalt ferrite nanoparticles are used in many aspects for certain properties such as antimicrobial activities the synthesized particles were characterized using different techniques such as UV Spectroscopy, SEM, FTIR, XRD,EDX. The antibacterial activity of cobalt ferrite nanoparticles is performed which shows remarkable results by increasing the inhibition zone for both E coli and Staphylococcus bacteria
Implementing Inkjet‐Printed Transparent Conductive Electrodes in Solution‐Processed Organic Electronics
Authors: Hermerschmidt Felix , Choulis Stelios A. , List‐Kratochvil Emil J. W.
Published: January 2019

Through the use of solution‐based materials, the field of printed organic electronics has not only made new devices accessible, but also allows the process of manufacture to move toward a high throughput industrial scale. However, while solution‐based active layer materials in these systems have been studied quite intensely, the printed electrodes and specifically the transparent conductive anode have only relatively recently been investigated. In this progress report, the use of metal nanoparticles within printed organic electronic devices is highlighted, specifically their use as replacement of the commonly used indium tin oxide transparent conductive electrode within organic photovoltaics (OPVs) and organic light emitting diodes (OLEDs). A cross fertilization between the applications is expected since an OPV device is essentially an inversely operated OLED. This report aims to highlight the use of inkjet‐printed nanoparticles as cost‐effective electrodes for printed optoelectronic applications and discusses methods to improve the conductive and interfacial properties. Finally, in an outlook, the use of these types of metal nanoparticle inks to manipulate light management properties, such as outcoupling, in the device is investigated.
Energy‐Efficient Organic Ferroelectric Tunnel Junction Memristors for Neuromorphic Computing
Authors: Majumdar Sayani , Tan Hongwei , Qin Qi Hang , van Dijken Sebastiaan
Published: January 2019

Energy efficiency, parallel information processing, and unsupervised learning make the human brain a model computing system for unstructured data handling. Different types of oxide memristors can emulate synaptic functions in artificial neuromorphic circuits. However, their cycle‐to‐cycle variability or strict epitaxy requirements remain a challenge for applications in large‐scale neural networks. Here, solution‐processable ferroelectric tunnel junctions (FTJs) with P(VDF‐TrFE) copolymer barriers are reported showing analog memristive behavior with a broad range of accessible conductance states and low energy dissipation of 100 fJ for the onset of depression and 1 pJ for the onset of potentiation by resetting small tunneling currents on nanosecond timescales. Key synaptic functions like programmable synaptic weight, long‐ and short‐term potentiation and depression, paired‐pulse facilitation and depression, and Hebbian and anti‐Hebbian learning through spike shape and timing‐dependent plasticity are demonstrated. In combination with good switching endurance and reproducibility, these results offer a promising outlook on the use of organic FTJ memristors as building blocks in artificial neural networks.