bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo
susceptibilities to ganaplacide and diversity in potential resistance mediators in Ugandan
Plasmodium falciparum
isolates
Authors: Kreutzfeld Oriana , Orena Stephen , Okitwi Martin , Tumwebaze Patrick K. , Byaruhanga Oswald , Katairo Thomas , Conrad Melissa D. , Legac Jennifer , Garg Shreeya , Crudale Rebecca , Aydemir Ozkan , Giesbrecht David , Nsobya Samuel L. , Blasco Benjamin , Duffey Maelle , Rouillier Melanie , Bailey Jeffrey A. , Cooper Roland A. , Rosenthal Philip J. 
Published: August 2024

ABSTRACT

Novel antimalarials are urgently needed to combat rising resistance to available drugs. The imidazolopiperazine ganaplacide is a promising drug candidate, but decreased susceptibility of laboratory strains has been linked to polymorphisms in the
Plasmodium falciparum
cyclic amine resistance locus (PfCARL), acetyl-CoA transporter (PfACT), and UDP-galactose transporter (PfUGT). To characterize parasites causing disease in Africa, we assessed
ex vivo
drug susceptibilities to ganaplacide in 750
P
.
falciparum
isolates collected in Uganda from 2017 to 2023. Drug susceptibilities were assessed using a 72-hour SYBR Green growth inhibition assay. The median IC
50
for ganaplacide was 13.8 nM, but some isolates had up to 31-fold higher IC
50
s (31/750 with IC
50
> 100 nM). To assess genotype-phenotype associations, we sequenced genes potentially mediating altered ganaplacide susceptibility in the isolates using molecular inversion probe and dideoxy sequencing methods. PfCARL was highly polymorphic, with eight mutations present in >5% of isolates. None of these eight mutations had previously been selected in laboratory strains with
in vitro
drug pressure and none were found to be significantly associated with decreased ganaplacide susceptibility. Mutations in PfACT and PfUGT were found in ≤5% of isolates, except for two frequent (>20%) mutations in PfACT; one mutation in PfACT (I140V) was associated with a modest decrease in susceptibility. Overall, Ugandan
P. falciparum
isolates were mostly highly susceptible to ganaplacide. Known resistance mediators were polymorphic, but mutations previously selected with
in vitro
drug pressure were not seen, and mutations identified in the Ugandan isolates were generally not associated with decreased ganaplacide susceptibility.
Prevalence and dynamics of antimalarial drug resistance mutations among the
Plasmodium falciparum
isolates in TAK Province, Thailand, during the period of 1998–2001
Authors: Thaloengsok Sasikanya , Chaisatit Chaiyaporn , Saingam Piyaporn , Lertsethtakarn Paphavee , Spring Michele , Sriwichai Sabaithip , Pholwat Suporn , Guler Jennifer L. , Houpt Eric R. , Vesely Brian A. 
Published: August 2024

ABSTRACT

Despite the overall decline in malaria cases in Thailand, continuous surveillance in endemic areas remains crucial. This retrospective analysis examined
Plasmodium falciparum
samples from Tak province, Thailand, collected in 1998, 1999, and 2001, to investigate the prevalence and evolution of antimalarial genotypic drug resistance. The study revealed a high prevalence of drug-resistant
P. falciparum
, particularly to mefloquine and sulfadoxine/pyrimethamine, with significant mutations in genes associated with resistance. Notably, mutations indicative of artemisinin resistance, such as those in the kelch13 gene, were detected at low frequencies, suggesting an evolving resistance pattern. The underlying cause of these resistance mutations appears to be the historical and widespread use of these antimalarial drugs, which exerted selective pressure on the parasite population. These findings underscore the necessity of ongoing surveillance and adaptive control strategies to manage drug resistance, guide treatment policies, and prevent potential outbreaks, even as malaria cases decrease. Continuous monitoring and research are imperative to sustain malaria elimination efforts and address the dynamic challenges posed by evolving drug-resistant strains.
Community organization and network complexity and stability: contrasting strategies of prokaryotic versus eukaryotic microbiomes in the Bohai Sea and Yellow Sea
Authors: Wang Xiaoxiao , Wang Hualong , Liang Yantao , McMinn Andrew , Wang Min 
Published: August 2024

ABSTRACT

Unraveling the effects of spatial gradients on microbiome assembly and association is a challenging topic that remains understudied in the coastal ecosystem. Here, we aimed to investigate the effects of spatial variation on the network complexity and stability of plankton microbiomes in the Bohai Sea and Yellow Sea. These seas serve as spawning and nursery grounds for economically important fisheries valued at billions of dollars annually. Environmental heterogeneity structures microbial communities into distinct spatial patterns, leading to complex direct/indirect relationships and broader ecological niches of bacterioplankton compared to microeukaryotic communities. Interestingly, salinity gradients positively influenced the richness of rare subgroups of bacterioplankton, while the rare microeukaryotic subgroups showed an opposite trend. Abundant subgroups of prokaryotic/eukaryotic microbiomes exhibited greater environmental niche breadth and lower phylogenetic distance compared to the rare subgroups. Stochastic processes contributed greatly to microbiome dynamics, and deterministic processes governed the bacterioplankton organization with a lower phylogenetic turnover rate. Compared to microeukaryotes, bacterioplankton exhibit higher network modularity, complexity, and robustness and lower fragmentation, and vulnerability. These observations offer vital insights into the anti-interference ability and resistance of plankton microbiomes in response to environmental gradients in terms of organization and survival strategy as well as their adaptability to environmental disturbances.

IMPORTANCE
An in-depth understanding of community organization and stability of coastal microbiomes is crucial to determining the sustainability of marine ecosystems, such as the Bohai Sea and Yellow Sea. Distinct responses between prokaryotic and eukaryotic microbiomes to spatial heterogeneity were observed in terms of geographical distribution, phylogenetic distance, niche breadth, and community assembly process. Environmental variations are significantly correlated with the dynamics of rare eukaryotic plankton subcommunities compared to prokaryotic plankton subcommunities. Deterministic processes shaped prokaryotic plankton community organization with a lower phylogenic turnover rate. Rare subgroups had noticeably higher phylogenetic distance and lower niche breadth than the corresponding abundant subgroups. Prokaryotic microbiomes had higher molecular network complexity and stability compared to microeukaryotes. Results presented here show how environmental gradients alter both the geographical characteristics of the microbial organization in coastal seas and also their co-occurrence network complexity and stability and thus have critical implications for nutrient and energy cycling.
Device associated complications in the intensive care unit
Authors: Hixson Roxana , Jensen Kristin Schwab , Melamed Kathryn H , Qadir Nida 
Published: August 2024

Abstract
Invasive devices are routinely used in the care of critically ill patients. Although they are often essential components of patient care, devices such as intravascular catheters, endotracheal tubes, and ventilators are a common source of complications in the intensive care unit. Critical care practitioners who use these devices need to use strategies for risk reduction and understand approaches to management when adverse events occur. This review discusses the identification, prevention, and management of complications of vascular, airway, and mechanical support devices commonly used in the intensive care unit.
Genetics of prostate cancer: a review of latest evidence
Authors: Hall Rose , Bancroft Elizabeth , Pashayan Nora , Kote-Jarai Zsofia , Eeles Rosalind A 
Published: August 2024

Prostate cancer (PrCa) is a largely heritable and polygenic disease. It is the most common cancer in people with prostates (PwPs) in Europe and the USA, including in PwPs of African descent. In the UK in 2020, 52% of all cancers were diagnosed at stage I or II. The National Health Service (NHS) long-term plan is to increase this to 75% by 2028, to reduce absolute incidence of late-stage disease. In the absence of a UK PrCa screening programme, we should explore how to identify those at increased risk of clinically significant PrCa.
Incorporating genomics into the PrCa screening, diagnostic and treatment pathway has huge potential for transforming patient care. Genomics can increase efficiency of PrCa screening by focusing on those with genetic predisposition to cancer—which when combined with risk factors such as age and ethnicity, can be used for risk stratification in risk-based screening (RBS) programmes. The goal of RBS is to facilitate early diagnosis of clinically significant PrCa and reduce overdiagnosis/overtreatment in those unlikely to experience PrCa-related symptoms in their lifetime. Genetic testing can guide PrCa management, by identifying those at risk of lethal PrCa and enabling access to novel targeted therapies.
PrCa is curable if diagnosed below stage III when most people do not experience symptoms. RBS using genetic profiling could be key here if we could show better survival outcomes (or reduction in cancer-specific mortality accounting for lead-time bias), in addition to more cost efficiency than age-based screening alone. Furthermore, PrCa outcomes in underserved communities could be optimised if genetic testing was accessible, minimising health disparities.
Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis
Authors: Ghezzi Laura , Tosti Valeria , Shi Lisa , Cantoni Claudia , Mikesell Robert , Lancia Samantha , Zhou Yanjiao , Obert Kathleen , Dula Courtney , Sen Monokesh K , Ge Anjie , Tolentino Miguel , Bollman Bryan , Don Anthony S , Matarese Giuseppe , Colamatteo Alessandra , La Rocca Claudia , Lepore Maria Teresa , Raji Cyrus A , Rahmani Farzaneh , Wu Gregory F , Naismith Robert T , Fontana Luigi , Cross Anne H , Salter Amber , Piccio Laura 
Published: August 2024

BackgroundCalorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures. This trial studied the effects of 12-week iCR on metabolic, immunological, and clinical outcomes in pwMS.MethodRelapsing-remitting MS participants were randomised to iCR or a control group. Study visits were conducted at baseline, 6 and 12 weeks. The primary outcome was reduction in serum leptin levels at 12 weeks. Feasibility and safety were assessed by diet adherence and adverse events (AEs). Secondary outcomes included changes in anthropometric and body composition measures, metabolic and immunologic profiling, and clinical measures. Mixed effects linear regression models were used to evaluate outcome differences between and within groups over time.ResultsForty-two pwMS were randomised, 34 completed the study (17/group). Leptin serum levels at 12 weeks were significantly lower in the iCR versus the control group (mean decrease −6.98 µg/dL, 95% CI: −28.02 to 14.06; p=0.03). Adherence to iCR was 99.5% and 97.2% at 6 and 12 weeks, respectively, and no serious AEs were reported. An increase in blood CD45RO+regulatory T-cell numbers was seen after 6 weeks of iCR. Exploratory cognitive testing demonstrated a significant improvement in the Symbol Digit Modality Test Score in the iCR group at 12 weeks.ConclusionsiCR has the potential to benefit metabolic and immunologic profiles and is safe and feasible in pwMS.Trial registration numberNCT03539094.
Occupational asthma in the salmon processing industry: a case series
Authors: Fagernæs Carl Fredrik , Lauritzen Hilde Brun , Tøndell Anders , Hassel Erlend , Bang Berit Elisabeth , Tjalvin Gro , Nordhammer Anna Beate Overn , Rodal Liv Bjerke , Slåstad Siri , Svedahl Sindre 
Published: August 2024

ObjectivesExposure to bioaerosols in salmon processing workers is associated with occupational asthma. IgE-mediated allergy and other disease mechanisms may be involved in airway inflammation and obstruction. Knowledge about disease burden, mechanisms, phenotypes and occupational exposure is limited.MethodsSalmon processing workers referred to our occupational medicine clinic from 2019 to 2024 were included in a patient register. They were investigated in line with current guidelines for the management of occupational asthma, categorised according to diagnostic certainty and characterised with a focus on symptoms, work tasks and clinical findings.ResultsA total of 36 patients were included, among whom 27 had typical symptoms of work-related asthma, and 21 were diagnosed with occupational asthma. Among those with occupational asthma, all worked in the filleting or slaughtering area at the time of symptom onset. Median latency from the start of exposure to symptom onset was 4 years. 14 (67%) of the patients with occupational asthma were sensitised to salmon. Three patients were sensitised to salmon skin but not salmon meat.ConclusionsOccupational asthma among salmon processing workers displays a heterogeneous clinical picture. IgE-mediated inhalation allergy towards various parts of the salmon seems to represent an important pathophysiological mechanism. However, some have occupational asthma with negative allergy tests. A comprehensive workup strategy including early initiation of serial peak expiratory flow and skin prick tests with various parts of the salmon should be considered. Although the incidence remains unknown, the substantial number of cases presented warrant increased efforts to reduce harmful exposure in the salmon processing industry.
The effect of foot immersion and neck cooling on cardiac autonomic function in older adults exposed to indoor overheating: a randomized crossover trial
Authors: McCourt Emma R. , Meade Robert D. , Richards Brodie J. , Koetje Nicholas J. , Santucci Nicholas B. , McCormick James J. , Boulay Pierre , Sigal Ronald J. , Kenny Glen P. 
Published: August 2024

Foot immersion and neck cooling are recommended cooling strategies for protecting heat-vulnerable persons during heat waves. While we recently showed that these strategies do not limit core temperature increases in older adults during prolonged heat exposure, we did observe small reductions in heart rate. Expanding on these findings, we examined the effects of foot immersion with and without neck cooling on cardiac autonomic function. Seventeen adults (9 females; 65–81 years) underwent 3 randomized, 6 h exposures to 38 °C and 35% relative humidity with: no cooling (control), foot immersion (20 °C water), or foot immersion with a wet towel (20 °C) around the neck. Cardiac autonomic responses were measured at baseline and end-exposure. These included heart rate variability, cardiac and systolic blood pressure responses to standing, indexed via the 30:15 ratio and supine-to-standing systolic pressure change, respectively, and baroreflex sensitivity during repeated sit-to-stand maneuvers. The 30:15 ratio was 0.04 [95% CI: 0.01, 0.07] greater with foot immersion and neck cooling (1.08 (SD: 0.04)) relative to control (1.04 (0.06); P = 0.018). Similarly, standing systolic blood pressure was elevated 9 [0, 17] mmHg with foot immersion and neck cooling ( P = 0.043). That said, neither difference remained statistically significant after adjusting for multiplicity ( Padjusted ≥ 0.054). No differences in 30:15 ratio or standing systolic blood pressure were observed with foot immersion alone, while heart rate variability and baroreflex sensitivity were unaffected by either cooling intervention. While foot immersion with neck cooling potentially improved cardiac autonomic responses in older adults exposed to simulated indoor overheating, these effects were small and of questionable clinical importance.
Scheduling meetings: are the odds in your favor?
Authors: Brown Katherine , Mathur Harsh , Narayan Onuttom 
Published: August 2024

Abstract
Polling all the participants to find a time when everyone is available is the ubiquitous method of scheduling meetings nowadays. We examine the probability of a poll with m participants and $$\ell $$
ℓ
possible meeting times succeeding, where each participant rejects r of the $$\ell $$
ℓ
options. For large $$\ell $$
ℓ
and fixed $$r/\ell ,$$

r
/
ℓ
,

we can carry out a saddle-point expansion and obtain analytical results for the probability of success. Despite the thermodynamic limit of large $$\ell ,$$

ℓ
,

the ‘microcanonical’ version of the problem where each participant rejects exactly r possible meeting times, and the ‘canonical’ version where each participant has a probability $$p = r/\ell $$

p
=
r
/
ℓ

of rejecting any meeting time, only agree with each other if $$m\rightarrow \infty .$$

m
→
∞
.

For $$m\rightarrow \infty ,$$

m
→
∞
,

$$\ell $$
ℓ
has to be $$O(p^{-m})$$

O
(

p

-
m

)

for the poll to succeed, i.e., the number of meeting times that have to be polled increases exponentially with m. Equivalently, as a function of p, there is a discontinuous transition in the probability of success at $$p \sim 1/\ell ^{1/m}$$

p
∼
1
/

ℓ

1
/
m

. If the participants’ availability is approximated as being unchanging from one week to another, i.e., $$\ell $$
ℓ
is limited, a realistic example discussed in the text of the paper shows that the probability of success drops sharply if the number of participants is greater than approximately 4.

Graphical abstract
Half Landau–Zener ramp to a quantum phase transition in a dissipative single spin model
Authors: Suzuki Sei 
Published: August 2024

Abstract
We study the dynamics of a single spin coupled to a bosonic bath at zero temperature driven by a ramp of the bias field. A single spin coupled to a bosonic sub-Ohmic bath exhibits a quantum phase transition at a certain strength of spin-boson coupling. When the bias field is ramped from a large value to zero at this critical coupling strength, the system initialized at the ground state ends up with a finite magnetization due to the critical slowing down near the transition. On the basis of the pulse-impulse approximation, we derive a scaling law between the residual magnetization and the ramp speed. The obtained scaling relation is examined using a numerical simulation based on the tensor network. The data are in favor of the scaling law to hold. We discuss the demonstration of our theoretical results by means of quantum simulation using the quantum annealer.

Graphical abstract
Relativistic periastron advance beyond Einstein theory: analytical solution with applications
Authors: Tedesco A. , Capolupo A. , Lambiase G. 
Published: August 2024

AbstractWe find a new solution to calculate the orbital periastron advance of a test body subject to a central gravitational force field for relativistic theories and models beyond Einstein. This analitycal formula has general validity that includes all the post-Newtonian (PN) contributions to the dynamics and is useful for high-precision gravitational tests. The solution is directly applicable to corrective potentials of various forms, without the need for numerical integration. Later, we apply it to the scalar tensor fourth order gravity (STFOG) and noncommutative geometry, providing corrections to the Newtonian potential of Yukawa-like form $$V(r)=\alpha \frac{e^{-\beta r}}{r}$$

V

(
r
)

=
α

e

-
β
r

r

, and we conduct the first analysis involving all the PN terms for these theories. The same work is performed with a Schwarzschild geometry perturbed by a Quintessence Field, leading to a power-law potential $$V(r)=\alpha _q {r}^q$$

V

(
r
)

=

α
q

r

q

. Finally, by using astrometric data of the Solar System planetary precessions and those of the S2 star around Sgr A*, we infer new theoretical constraints and improvements in the bounds for $$\beta $$
β
. The resulting simulated orbits turn out to be compatible with general relativity.
Why is $${}^{208}_{82}\textrm{Pb}$$ the heaviest stable nuclide?
Authors: Kosyakov B. P. , Popov E. Yu , Vronskiĭ M. A. 
Published: August 2024

AbstractIn an effort to understand nuclei in terms of quarks we develop an effective theory to low-energy quantum chromodynamics in which a single quark contained in a nucleus is driven by a mean field due to other constituents of the nucleus. We analyze the reason why the number of d quarks in light stable nuclei is much the same as that of u quarks, while for heavier nuclei beginning with $$\mathrm{{}^{40}_{20}Ca}$$

20
40

Ca

, the number of d quarks is greater than the number of u quarks. To account for the finiteness of the periodic table, we invoke a version of gauge/gravity duality between the dynamical affair in stable nuclei and that in extremal black holes. With the assumption that the end of stability for heavy nuclei is dual to the occurrence of a naked singularity, we find that the maximal number of protons in stable nuclei is $$Z_{\max }^{\textrm{H}}\approx 82$$

Z

max

H

≈
82

.
LTβR Agonism Promotes Antitumor Immune Responses via Modulation of the Tumor Microenvironment
Authors: An Disi , Chen Guoying , Cheng Wei-Yi , Mohrs Katja , Adler Christina , Gupta Namita T. , Atwal Gurinder S. , DiLillo David J. , Daly Christopher , Lin John C. , Kuhnert Frank 
Published: August 2024

Abstract
The presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune checkpoint blockade in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to antitumor responses may facilitate the development of improved treatment strategies. Lymphotoxin β receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and immune checkpoint blockade treatment to augment tumor-associated HEV formation. In this study, we demonstrated that LTβR signaling modulates the tumor microenvironment via multiple mechanisms to promote antitumor T-cell responses. Systemic activation of the LTβR pathway via agonistic antibody treatment induced tumor-specific HEV formation, upregulated the expression of TLS-related chemokines, and enhanced dendritic cell (DC) and T-cell infiltration and activation in syngeneic tumor models. In vitro studies confirmed direct effects of LTβR agonism on DC activation and maturation and associated DC-mediated T-cell activation. Single-agent LTβR agonist treatment inhibited syngeneic tumor growth in a CD8+ T-cell–dependent and HEV-dependent manner, and the LTβR agonist enhanced antitumor effects of anti-PD-1 and CAR T-cell therapies. An in vivo tumor screen for TLS-inducing cytokines revealed that the combination of LTβR agonism and lymphotoxin ⍺ expression promoted robust intratumoral TLS induction and enhanced tumor responses to anti-CTLA4 treatment. Collectively, this study highlights crucial functions of LTβR signaling in modulating the tumor microenvironment and could inform future HEV/TLS-based strategies for cancer treatments.
Significance: LTβR mediates tumor-specific high endothelial venule formation and immunomodulation of the tumor microenvironment that promotes antitumor immune responses, supporting LTβR agonism as an approach to enhance the antitumor efficacy of immunotherapies.