bluuebunny/crossref_metadata_2025 huggingface dataset:
The population pharmacokinetics and dose optimization of polymyxin B in critically ill patients with or without extracorporeal membrane oxygenation
Authors: Ye Qinghua , Wang Qianlin , Chen WenQian , Zhang Ruihao , Chen Ziying , Li Pengmei , Zhang Xianglin , Zhan Qingyuan , Wang Chen
Published: January 2024

Aims: The objectives of this study were to determine the population
pharmacokinetics (PK) model of polymyxin B in critically ill patients
with or without extracorporeal membrane oxygenation (ECMO) support that
investigated the influence of ECMO on PK variability and to identify an
optimal dosing strategy. Methods: Forty-four critically ill patients
were enrolled, including eight patients with ECMO support. Eight serial
serum samples were collected from each patient at steady state. The
population PK was determined using NONMEM and Monte Carlo simulation was
performed to evaluate the exposures of different dosing regimens.
Results: The PK analyses included 342 steady-state concentrations and a
two-compartment model was optimal for polymyxin B PK data modelling. In
the final model, creatinine clearance (CLCR) was the significant
covariate on CL (typical value 1.27 L/h; between-subject variability
15.1%) and ECMO did not show a significant impact on the polymyxin B
PK. Additionally, we found that the PK parameter estimates of patients
with and without ECMO support were mostly similar. Based on Monte Carlo
simulations, the dose escalation of polymyxin B in patients with
increased CLCR improved the probability of achieving required exposure.
For patients with CLCR≤120 mL/min, a dosage regimen of 100mg every 12h
may represent the optimal regimen at an MIC of 1 mg/L. Conclusion: The
impact of ECMO on the polymyxin B PK is likely to be minimal. Our study
showed a potential relationship between CLCR and polymyxin B CL, and the
dose of polymyxin B should be adjusted in patients with increased CLCR.
Association between Influenza-like illness and acute myocardial infarction patients: A case-control study
Authors: Mohseni Seyed Morteza , Ebrahimpour Soheil , Ganji Ghasem Faghanzadeh , Babazadeh Arefeh , Amin Kamyar , Barary Mohammad , Esmailzadeh Malihe , Sabbagh Parisa , Shokri Mehran
Published: January 2024

Background: Acute myocardial infarction (AMI) is the leading cause of
death worldwide. Seasonal Influenza can lead to cardiovascular
complications. Thus, the association between Influenza and
cardiovascular events has been of interest recently. Hypothesis:
Therefore, this study aimed to investigate recent influenza-like
illnesses (ILI) in acute myocardial infarction (AMI) patients compared
to other hospitalized patients as the control group during the cold
season in the north of Iran. Methods: This retrospective case-control
study included 300 patients (150 AMI patients and 150 controls) aged ≥
50 years hospitalized for acute myocardial infarction (AMI) or other
conditions between September 22, 2019, and March 15, 2020. Patients in
each group were frequency-matched for gender and age range. The primary
exposure was a recent ILI (fever ≥ 37.8°C, cough, and sore throat) in
the past month. Results: The patients’ mean age was 64.42 ± 9.47 years,
with a range of 50-94 years. Overall, forty-five (15%) patients of 300
participants had diseases that met the ILI criteria. The AMI group
patients significantly reported more ILI than controls (adjusted OR:
3.04, 95% CI: 1.02 to 9.09, p < 0.001). On the other hand,
patients who received the influenza vaccine were significantly less
likely to have an acute myocardial infarction than those who did not
receive the vaccine (adjusted OR: 0.02, 95% CI: 0.001 to 0.38, p =
0.006). Conclusion: In conclusion, the present study demonstrates that
ILI can increase the risk of AMI. Also, it was confirmed that Influenza
vaccination could reduce the risk of AMI.
Chromosome-level genome assemblies of deep-sea eels shed light on the adaptation to the deep-sea environments
Authors: chen jie , He Li-sheng , Lv wenqi , Sun ning , Bo Jing , Wang cheng , Xu wenjie , Hu mingliang , Gan Xiao ni , He shunping , Fang chengchi
Published: January 2024

It is relatively poorly understood how vertebrates can survive and
thrive in deep-sea environments (depths below 3,000 m that are
characterized by high hydrostatic pressures, low temperatures, and
sparse food resources). In this study, we compared the genomes of two
deep-sea eels (Ilyophis sp1 and Ilyophis sp2 living below 3,000 m)
against those of shallow-water closely related eels and other teleosts
to examine the genetic bases of their adaptations to the deep-sea.
Phylogenetic analyses showed that these two deep-sea eels diverged from
European eels ~111.9 million years ago (Mya) and likely
evolved into two separate groups ~3.59 Mya. Comparative
genomic analyses reveal that: (1) the positively selected cytoskeleton
gene TUBGCP3 and the expanded family MLC1 may improve the cytoskeleton
stability under high pressure; (2) the changes in protein sequences of
Acox1 may enhance cell membrane fluidity and maintain transport activity
under high pressure; (3) functional mutation of the translation gene
HARS in deep-sea eels may change its translation ability to resist the
influence of low temperature on translation-related enzymes; and (4)
energy metabolism under a food-limited environment may be increased by
expanded and positively selected gene enrichment in AMPK and mTOR
signaling pathways. Our results provide insights into the underlying
genetic basis and molecular evolution of deep-sea vertebrates.
Growth-promoting Effect of Graphene Oxide on Tissue Culture Seedlings of Poplar
Authors: Zhang Runxuan , Xing Baoyan , Bao Yayan , Liu Haiyan , Huang Jingting , Xue Binlong , Li Jianfeng , Haiyan Wang , Yao Jianzhong , Zhou Xinjun , Oberc Christopher , Li Paul
Published: January 2024

Graphene oxide (GO) is a widely used nanomaterial, whose unique
carbon-based structure bears abundant oxygen-containing functional
groups. An increasing number of investigations have been performed on
the effects of GO on plants due to its extensive use in various fields.
In this work, under the optimized GO concentration (6 mg/L), we found
that GO promoted the growth rate of the root of poplar. TEM images
depicted that the plasmolysis and an increased number of starch grains
were the two major physiological changes in the root cell samples. GO
adhered to the cell membrane on the inner side of the cell wall and
enhanced the toughness of the adventitious root. And the activity of
oxidoreductases were measured and SOD, POD were found to increase
significantly compared with the control group, but the increase of CAT
was not obvious. Related gene expression was enhanced at low
concentration of GO, but inhibited at high concentration. Our results
indicate the possible usage of GO as enhancers in the growth of poplar
tissue culture seedlings.
Effect of PCSK9 inhibitor on blood lipid levels in patients with high and very-high CVD risk: a systematic review and meta-analysis
Authors: Zhang Yue , Suo Yanrong , Yang Lin , Zhang Xiaolu , Yu Qun , Zeng Miao , Zhang Wenlan , Jiang Xijuan , Wang Yijing
Published: January 2024

Objectives We aimed to investigate the effects of PCSK9
inhibitor on blood lipid levels in patients with high and very-high
cardiovascular risk. Design 14 trials (n=52,586 patients)
comparing treatment with or without PCSK9 inhibitors were retrieved from
PubMed and Embase updated to 1st Jun 2021. The data quality of included
studies was assessed by two independent researchers using the Cochrane
systematic review method. All-cause mortality, cardiovascular mortality
and changes in serum LDL-C, TC, TG, ApoB, LP (a), Non HDL-C, HDL-C and
ApoA1 from baseline were analyzed using Rev Man 5.1.0 software.
Results Compared to treatments without PCSK9 inhibitor,
addition of PCSK9 inhibitors (evolocumab and alirocumab) had obvious
decreasing effects on the levels of LDL-C [MD=-46.86, 95% CI (-54.99
to -38.72), P<0.00001], TC [MD=-31.92, 95% CI
(-39.47 to -24.38), P<0.00001], TG [MD=-8.13, 95%
CI (-10.48 to -5.79), P<0.00001], LP(a) [MD=-26.69,
95% CI (-27.93 to -25.44), P<0.00001], Non HDL-C
[MD=-42.86, 95% CI (-45.81 to -39.92), P<0.00001]
and ApoB [MD=-38.44, 95% CI (-42.23 to -34.65),
P<0.00001] in high CVD risk patients. Conversely,
changes of HDL-C [MD = 6.27, CI (5.17 to 7.36), P <
0.00001] and ApoA1 [MD = 4.33, 95% CI (3.53 to 5.13), P
< 0.00001] from baseline were significantly more in high CVD
risk patients who received PCSK9 inhibitors treatment.
Conclusion Addition of PCSK9 inhibitors to standard therapy
resulted in definite improvement in blood lipid levels than those
therapies without its addition.
Distribution of Wolbaichia strains in Stegomyia albopicta, Vector of dengue and chikungunya in Kerala, India
Authors: Shah Adil , Saima Syed
Published: January 2024

Wolbachia are a group of intracellular bacteria known to be prevalent
among arthropods. Wolbachia infection cause declines of host
populations, and also gives rise to host resistance to a wide range of
pathogens. Over the past few decades, Wolbachia is used as a biological
tool to control mosquito vectors. The study was aimed to identify
Wolbachia strains in field collected St. albopicta from different
breeding sites in Kerala. A total of 105 Samples were collected from 3
different areas with different breeding sites, areca nut planation in
Kasaragod (North Kerala), rubber and pineapple plantation in Kottayam
(Central Kerala) and tyres and containers in Thiruvananthapuram (South
Kerala). The positive samples showing clear intensity were selected from
general as well as strain specific samples for sequencing. The samples
prior to sending for sequencing was extracted and purified using gel
extraction kit and lyophilized. The sequences were aligned using
ClustalW software. Then further phylogenetic analysis were made using
MEGA 5 software. The positive samples were found to have 95% A(wAlbA)
and B(wAlbB) super infection with 5% and 3% single infection of wAlbA
and wAlbB strains respectively.
Excessive and asymmetrical removal of heterozygous sites by maxSharedH biases downstream population genetic inference: Implications for hybridization between two primroses
Authors: Zhang Jie , Pina-Martins Francisco , Jin Zushi , Cha Yongpeng , Liu Zuyao , Peng Junchu , Zhao Jianli , Li Qingjun
Published: January 2024

Techniques of reduced-representation sequencing (RRS) have
revolutionized ecological and evolutionary genomics studies. Precise
establishment of orthologs is a critical challenge for RRS, especially
when a reference genome is absent. The proportion of shared heterozygous
sites across samples is an alternative criterion for filtering paralogs,
as divergent lineages should be less likely to share heterozygosity. In
the prevailing pipeline for variant calling of RRS data - PYRAD/IPYRAD,
maxSharedH is an often overlooked parameter with implications to
detecting and filtering paralogs according to shared heterozygosity.
Using empirical GBS data of two primroses (Primula alpicola Stapf
and Primula florindae Ward) and their putative hybrids, we
explore the impact of maxSharedH on filtering paralogs and
further downstream analyses. Our study sheds light on the simultaneous
validity and risk of filtering paralogs using maxSharedH, and its
significant effects on downstream analyses of outlier detection,
population assignment, and demographic modelling, emphasizing the
importance of attention to detail during bioinformatics processes. The
mutual confirmation between results of population assignment and
demographic modelling in this study suggested maxSharedH = 0.10
has a potentially excessive and asymmetrical effect on the removal of
truly shared heterozygous sites as paralogs. These results indicate that
hybridization origin hypotheses of putative hybrids represented by
results with maxSharedH = 0.25 and 0.50 are more credible. In
conclusion, we revealed the critical hazard of paralogs filtration
according to sharing heterozygosity at first, so that we propose to use
specific protocols, rather than maxSharedH, to filter potential
paralogs for closely related lineages.
Population Pharmacokinetics of Isoniazid: A Systemic Review
Authors: Tan Wen Rui , Ghadzi Siti Maisharah Sheikh , Harun Sabariah Noor , Al Irfhan Ali Hyder
Published: January 2024

Background. Isoniazid (INH) is one of the drugs in the classical therapy
for pulmonary tuberculosis. Several INH population pharmacokinetic
models were established in the last ten years. This systemic review was
performed i) to summarize published population pharmacokinetic (PPK)
models of INH and ii) to summarize and explore identified covariates
influencing the INH pharmacokinetic models. Methods. A search of
publication for population pharmacokinetic analyses of INH either in
healthy volunteers or patients from 2011 to 2021 was conducted in PubMed
databases. Reviews, methodology articles, non-compartmental analysis,
in-vitro, and animal studies, were excluded. Results. 12 studies were
included in this review. INH pharmacokinetics was described as
two-compartment with first-order absorption and elimination in most of
the included studies. In most of the studies, N-acetyltransferase 2
(NAT2 ) genotype polymorphism (n=11) was the most common identified
covariates affecting INH pharmacokinetic parameters. Body weight (n=2)
and body mass index (BMI) (n=1) were the most common significant
covariates retained in the final model. Conclusions . The population
pharmacokinetic of INH has been extensively reviewed and the published
PPK models of INH and its parameters were summarized in this review. The
PPK variability of INH was reported to be explained mainly by the NAT2
genotype polymorphism on the clearance (CL) parameter. This review shows
that to optimise and rationalise the dosing regimen of INH, a patient’s
NAT2 genotype should be considered. Body weight and BMI value should be
taken into consideration when making dosing adjustments for INH to
achieve therapeutic range.
Histone deacetylase CsHDA6 mediates the regulated formation of the anti-insect metabolite α-farnesene in tea ( Camellia sinensis )
Authors: Wu Shuhua , Yang Yuhua , Chen Jiaming , Li Jianlong , Jian Guotai , Yang Jie , Mao Kaiquan , Zeng Lanting , Gu Dachuan
Published: January 2024

Mechanical wounding is a common factor inducing herbivore-induced plant
volatiles (HIPVs) production during almost all insect infestations.
Additionally, α-farnesene is one of the HIPVs that accumulate in tea
plants following infestations by most insects. However, the specific
mechanism underlying the wounding-regulated accumulation of α-farnesene
remains unclear, especially at the level of epigenetic regulation.
Moreover, α-farnesene in tea plants has not been functionally
characterized. In this study, we observed that histone deacetylase
inhibitors treatment can induce the accumulation of α-farnesene.
Subsequent analyses of protein interactions and GUS activity revealed
that the histone deacetylase CsHDA6 can interact directly with CsMYC2,
which is an important transcription factor in the jasmonic acid (JA)
pathway, and co-regulate the expression of the key α-farnesene synthesis
gene CsAFS. Wounding caused by an insect infestation affected
CsHDA6 production at the transcript and protein levels, while also
inhibiting the binding of CsHDA6 to the CsAFS promoter. The
resulting increased acetylation of histones H3 and H4 in CsAFS
enhanced the expression of CsAFS and the accumulation of
α-farnesene. Furthermore, a large amount of α-farnesene can protect tea
plants from tea geometrid infestations by attracting the natural enemy
of the insect pest. In conclusion, our study demonstrated the effect of
histone acetylation on the production of tea plant HIPVs and revealed
the importance of the CsHDA6-CsMYC2 transcriptional regulatory module
for the accumulation of the anti-insect metabolite α-farnesene in tea
plants following an insect infestation.
EP ROUNDS Symptomatic bradycardia: hold the beta blocker?
Authors: Littmann Laszlo
Published: January 2024

Per journal policy, no abstract is required for the section EP Rounds.
Rocket-shape crossing technique: a combination of lead extraction and modified venoplasty for device upgrade with venous occlusion
Authors: Morita Junji , Kondo Yusuke , Haraguchi Takuya , Nagashima Michio , Kitai Takayuki , Fujita Tsutomu
Published: January 2024

Introduction A 54-year-old man with superior vena cava occlusion was
referred to our institution for an upgrade to cardiac resynchronization
therapy defibrillator. Methods and results Right ventricular lead
extraction with modified venoplasty, rocket-shape crossing technique
(RCT), was performed. In RCT, the integration of the inflated balloon,
halfway inside the laser sheath, and the laser sheath are advanced
through the occlusion like a “rocket-shape crossing”. Conclusion
Modified venoplasty can be useful during device upgrades in patients
with venous occlusion.
Enigmatic cysts discovered in a population of European salamanders
Authors: Manenti Raoul , Mercurio Silvia , Melotto Andrea , Barzaghi Benedetta , Epis Sara , Tecilla Marco , Pennati Roberta , Scarì Giorgio , Ficetola Gentile Francesco
Published: January 2024

New pathologies are causing dramatic declines and extinctions of
multiple amphibian species. In 2013, we found fire salamanders with
undescribed cysts at the throat level in one population in Northern
Italy, which existence is not reported in amphibians yet. With the aim
of describing this novel phenomenon, we performed repeated surveys to
assess the frequency of affected salamanders from 2014 to 2020, and
integrated morphological, histological and molecular analyses. Cysts
affected up to 22 % of salamanders of the study population and started
spreading to nearby populations. Cysts are formed by mucus surrounding
cells about 10 μm long, characterized by numerous undulipodia.
Morphological and genetic analyses did not yield a clear match with any
described organism or salamander cell. The occurrence of these cysts
calls for more studies on the origin and impact on wild populations.
Factors associated with husband’s involvement in birth preparedness and complication readiness in urban slums of Mangaluru, India: a cross-sectional community-based study
Authors: Shivalli Siddharudha , Murugesh Ramya , Kaup Soujanya , Narayanswamy Anusha
Published: January 2024

Objective: To assess the level of husband’s involvement in and the key
factors associated with birth preparedness and complication readiness
(BPCR) in urban slums of Mangaluru, Karnataka, India Design:
Cross-sectional community-based study Setting: 21 urban slums in
Mangaluru, India Population: Resident men in 21 urban slums (whose wife
had childbirth/s within one year) selected by multi-stage random
sampling. Methods: We interviewed eligible husbands using a
semi-structured questionnaire to collect data on socio-demography,
wife’s obstetric and antenatal care (ANC) details, and husband’s
involvement in six key BPCR practices. Main Outcome Measure: Husband’s
optimal BPCR involvement (i.e. followed minimum four of six practices).
Results: Of the 214 eligible husbands, 207 participated (96.7%-response
rate) and 50.2% (95%CI:43.3-57.2) displayed optimal BPCR involvement.
98.6% of wives had ≥4 ANC visits, and 91.8% of husbands escorted wives
for ANC at least once. Literate wife (AdjOR:6.5; 95%CI:1.4-28.9), ANC
in first trimester (AdjOR:7.8; 95%CI:1.01-61.1), and receiving adequate
advice on BPCR (AdjOR:47.8; 95%CI:10.4-219.8) were associated with
husband’s optimal BPCR involvement. Conclusions: Only half of the
husbands showed optimal BPCR involvement, and it was associated with
wife’s literacy, ANC in first trimester, and receiving adequate BPCR
information. Although nine of 10 husbands escorted their wives for ANC
at least once, only about one-fourth of them received adequate
information on BPCR, emphasising missed opportunities for health
education during ANC. Grassroots health workers should engage husbands
during ANC and explain various BPCR practices. Further qualitative
research may help develop socio-culturally contextualised strategies to
enhance the husband’s role in BPCR.
Rhegmatogenous Retinal Detachment with Spontaneous Dialysis of the Ora Serrata in Neurofibromatosis Type 1: A Case Report
Authors: Shrestha Richa , Bhatt Swechha , Shrestha Pooja , Sapkota Prakash , Keshari Rajani , Manandhar Anu , Bhattarai Iwa
Published: January 2024

Here, we present a case of a 36-year-old man with Neurofibromatosis Type
1 with spontaneous dialysis of ora serrata with no prior history of
ocular trauma, possibly linked to abnormal cell-matrix formation in
Neurofibromatosis Type 1.
Clinical Features and Treatment Strategies of Precursor B-cell Lymphoblastic Leukemia with C-myC Rearrangement in Childhood
Authors: Wang Xiang , Huang Jun , Wu kefei , Yu Lisha , Pan Ci , Chen Jing , Shen Shuhong , Chen Changcheng , Mi Qiang
Published: January 2024

Background: “Rare cases of Burkitt leukemia/lymphoma (BL) exhibiting a
precursor B-cell phenotype (termed herein pre-BLL) were admitted by WHO
Classification of Hematopoetic and Lymphoid Tissue, recent evidence
suggests that these neoplasms genetically and epigenetically resemble
precursor B-cell leukemia/lymphoma (pB-acute lymphoblastic
leukemia/lymphoblastic lymphoma (ALL)/LBL) rather than BL. The clinical
features and treatment of childhood pre-BLL with C-myC rearrangement are
poorly understood. Methods：The clinical features, treatment strategies
and follow-up information of 9 cases with pre-BLL diagnosed by Shanghai
Children’s Medical Center affiliated to Shanghai Jiao Tong University
School of Medicine from 2011 to 2020 were retrospectively analyzed.
Results: All the 9 cases were confirmed to be pre-BLL by flow cytometry
and fluorescence in situ hybridization, morphological classification
were L2/L3, immunophenotype was CD10, CD19 positive, CD20, TDT, CD34
selective expression, sIgM negative, Kappa and Lambda light chain
negative. Most of the pre-BLL cases were accompanied by elevated lactate
dehydrogenase (LDH), uric acid levels. 5 cases received intensive
chemotherapy with overlapping regimen, and all achieved sustained
remission except for 1 case relapse and death. Among the 4 cases who
received low-intensity chemotherapy for acute lymphoblastic leukemia, 2
cases died due to early relapse of the disease. Conclusions: Pre-BLL
cases are rare. and intensive chemotherapy treatment according to
protocols for mature B-cell NHL. Currently, the treatment strategies are
still controversial. Considering the small number of cases, multi-center
clinical studies should be actively carried out to find a standard
treatment plan.
Evolutionary analysis of THAP9 transposase: conserved regions, novel motifs
Authors: Rashmi Richa , Nandi Chandan , MAJUMDAR sharmistha
Published: January 2024

THAP9 is a transposable element-derived gene that encodes the THAP9
protein, which is homologous to the Drosophila P-element
transposase (DmTNP) and can cut and paste DNA. However, the exact
functional role of THAP9 is unknown. Here, we perform evolutionary
analysis and extensive in silico characterization of THAP9,
including predicting domains and putative post-translational
modification sites. We predict previously unreported mammalian-specific
post-translational modification sites that may play a role in the
subcellular localization of THAP9. We also observe that although THAP9
has evolved under a strong pervasive purifying selection, yielding high
conservation of THAP9, there are distinct class-specific conservation
patterns of key functional residues in certain domains. Furthermore,
investigation of THAP9 expression profiles in various cancer and matched
normal datasets demonstrated underexpression and overexpression in
testicular cancers and thymic epithelial tumors, respectively, thus
suggesting a possible role of THAP9 in cancer.
Prolonged Prothrombin Time Does Not Correlate with Clinical Bleeding Symptoms in Newly Diagnosed Pediatric Leukemia Patients
Authors: Al-Ghafry Maha , Haimed Abraham , Su Julia , Acharya Suchitra
Published: January 2024

Prolonged prothrombin time (PT) and/or activated partial thromboplastin
time (aPTT) are frequently seen in newly diagnosed pediatric leukemia
patients (NDPLP), which can lead to delayed diagnostic and therapeutic
procedures due to concern for bleeding. In this single center
retrospective study of NDPLP we analyzed these parameters in 93 patients
(aged 1-21 years). None had a personal history of bleeding, but 33.3%
had bleeding symptoms within 30 days of presentation, predominantly
mucosal bleeding (80.6%) and petechiae (64.5%). Median laboratory
values at diagnosis: white blood cell count 15.7, hemoglobin 8.1,
platelets 64, PT 13.2, and a PTT 31. Red blood cells were administered
in 41.2%, platelets in 52.9%, FFP in 7.8%, and vitamin K in 21.6%
based on institutional cut-off values for replacement or clinical
symptoms. Prolonged PT was found in 54.8% of patients (factor VII
33.1% (interquartile range [IQR] 19.4-50.5), while aPTT was
prolonged in 5.4%. Anemia and thrombocytopenia did not correlate with
prolonged PT (p=0.73 and p=0.18 respectively), or prolonged aPTT (p=0.52
and 0.42). Leukocytosis and neutrophilia showed significant correlation
with elevated PT (p<0.001 and <0.01 respectively),
but not aPTT (p=0.3 and 0.5). Bleeding symptoms upon presentation did
not correlate with prolonged PT (p=0.83), prolonged aPTT (p=1) or anemia
(p=0.06) but had significant correlation with thrombocytopenia
(p=<0.0001) and elevated AST (p=0.05). Therefore, a prolonged
PT in NDPLP may not necessitate the reflexive use of blood product
replacement in the absence of significant bleeding, which is likely
related to leukocytosis than to a true coagulopathy.
Trade-offs in dormancy phenology in endotherms and ectotherms
Authors: Constant Théo , Dobson F. , Giroud Sylvain , Habold Caroline
Published: January 2024

Seasonal dormancy (e.g. diapause, hibernation) is widely considered an
adaptation for surviving life-threatening conditions during part of the
year. However, the selective pressures acting on dormancy are poorly
studied. An underestimated common aspect is the high survival rate
during dormancy compared to the active period, perhaps due to the
reduced risk of predation and competition. We hypothesize that dormancy
phenology is influenced by a trade-off between the reproductive benefits
of being active and the survival benefits of being dormant. Using a
phylogenetic comparative method and more than 20 hibernating mammals, we
find that the sex difference in hibernation phenology is explained by
sex differences in physiological constraints that may influence this
trade-off. Consistent with the trade-off hypothesis, the sex that spends
more time in an activity directly associated with reproduction (e.g.
testicular maturation, gestation) or indirectly (e.g. recovery from
reproductive stress) spends less time in hibernation. Some of the tested
parameters such as testes maturation or a late mating period during the
active season also influence the sex difference in dormancy phenology
among ectotherms (e.g. reptiles, invertebrates). We then gathered
evidence that dormancy in non-life-threatening periods that are
unfavorable for reproduction may be more widespread than previously
thought.
Thermal Performance Optimization of Miniature Heat Sink Devices Using Hybrid Nanofluid
Authors: SRIVASTAVA KARTIK , sahoo rashmi
Published: January 2024

The present numerical investigation carried out to obtain the dimensions
and parameters for thermal performance optimization of miniature heat
sink devices using hybrid nanofluid. Microchannels and minichannels of
the surface area of 1x1cm2 and 4x4cm2 were optimized. Water and 1% vol.
fraction of Al2O3-MWCNT (50:50)/water hybrid nanofluid was used as
coolants. In this study, the heat sinks are thermally optimized on a
numerical basis by using basic governing equations, applying boundary
conditions and assumptions, and carrying out the optimization scheme.
Also, the effect of pressure drop with friction factor, Nusselt number,
heat transfer coefficient, and fin efficiency of channel walls on
Reynolds number are studied, and comparative analysis is accomplished.
Results revealed that a heat sink with lower total thermal resistance
would consume more pumping power. However, the thermal performance of
the coolant is improved by hybrid nanofluids with a marginal rise in the
pumping power
Spatially explicit dynamic N-mixture models with interspecific interactions
Authors: Zhao Qing , Fuller Angela , Royle J.
Published: January 2024

Interspecific interactions and movement are key factors that drive the
coexistence of metapopulations in heterogenous landscapes. Yet, it is
challenging to understand these factors because separating movement from
local population processes relied on capture-based data that are
difficult to collect. Recent development of spatially explicit dynamic
N-mixture models (SEDNMs) made it possible to draw inference on local
population growth and movement using count data of unmarked populations.
Here, we further developed SEDNMs to account for interspecific
interactions and both false positive and false negative observation
errors. Simulations showed that the models provide unbiased parameter
estimates regardless of the ecological system (competition,
predator-prey), observation process (binomial, Poisson), and sampling
situation. Case studies further demonstrated the capabilities of these
models in revealing important ecological processes including
competition, predator-prey interactions, movement patterns, and
differential habitat preferences. The flexible structures of these
models make them highly adaptive and relevant in population and
community ecology.
Urinary Clearance of 11-Nor-9-Carboxy-Δ9-Tetrahydrocannabinol (THCCOOH): A Detailed Pharmacokinetic Analysis
Authors: Sempio Cristina , Huestis Marilyn , Kaplan Bruce , Klawitter Jost , Christians Uwe , Henthorn Thomas
Published: January 2024

Background. Urine is a common matrix for screening for cannabis use.
Urine assays typically measure total THCCOOH concentrations after
hydrolysis cleaves the glucuronide. Urine THCCOOH concentration is
adjusted by urine creatinine concentration or specific gravity, to
account for variable hydration states. Therefore, we performed a
population pharmacokinetic analysis of the urinary THCCOOH excretion,
urinary flow rate, and creatinine excretion rate data. Methods. Urine
was obtained over 168 hours from 6 subjects who smoked low (15.8 mg) and
high dose (33.8 mg) THC cigarettes on two occasions. Samples were
analyzed for THCCOOH concentration by GC/MS and volume, time and
creatinine concentration measured. A population pharmacokinetic model of
the urinary clearance of THCCOOH was created from these data and
potential covariates of urine creatinine concentration and urine
creatinine excretion rate were assessed. Results. Elimination clearance
of THCCOOH was estimated as 0.104 ± 0.088 L/min and its urinary
clearance was 0.0022 ± 0.0015 L/min. Total urine excretion of THCCOOH
was estimated a 2.3%. Urine flow rate and urine creatinine
concentrations were significantly correlated, r2 0.35. Creatinine
excretion rate was 129.6 ± 71.0 mL/min and the intra-subject variability
was 31-52% (SD%) during the week. Urinary creatinine excretion rate
was a significant covariate for the urinary clearance of THCCOOH.
Conclusions. Creatinine Clearance is a significant covariate for urinary
THCCOOH clearance. Only 2-3% of bioavailable THC is excreted as THCCOOH
and THCCOO-glucuronide via the urine. Correction of urine drug and/or
metabolite concentration with urine creatinine concentration or specific
gravity may be more problematic than previously appreciated.
Modeling the effect of probiotics on tilapia lake virus (TiLV)-infected farmed tilapia
Authors: Yang Ying-Fei , Yamkasem Jidapa , Surachetpong Win , Lin Yi-Jun , Shu-Han * , Lu Tien-Hsuan , Chen Chi-Yun , Wang Wei-Min , Liao Chung-Min
Published: January 2024

Probiotics have been used as one of the most promising dietary
interventions to alleviate disease transmission in aquaculture. However,
there are limited studies on probiotic uses in modulating the highly
contagious virus such as tilapia lake virus (TiLV) that is seriously
threatening global tilapia production. We assessed commercially
available probiotic supplement use in TiLV-infected tilapia and
performed mortality and cohabitation assays. We developed a mechanistic
approach to predict dose-response interactions of probiotic effects on
mortality and innate immune gene response. We used a
susceptible-infected-mortality disease model to assess key
epidemiological parameters known as transmission rate and basic
reproduction number ( R) based on our viral
load dynamics data. We found that the most marked benefits of probiotics
are significantly associated with immune system enhancements
(~30%) and disease transmission (~80%)
and R (~70%) reductions in
tilapia populations, resulting in a higher tolerance of farming
densities (~400 folds) in aquaculture. These findings
provide early insights as to how probiotic use-related factors may
influence TiLV transmission and the immune responses in TiLV-infected
tilapia. Our study facilitates understanding the mode of action of
probiotics in disease containment and predicting better probiotic
dosages in diet and supplements to achieve the optimal culturing
conditions. Overall, our analysis assures that further study of
rationally designed and targeted probiotics, or mechanistic modeling is
warranted on the basis of promising early data of this approach.
Stability of a flexible missile and asymptotics of the eigenvalues of fourth order boundary value problems
Authors: Zinsou Bertin
Published: January 2024

Fourth order problems with the differential equation
$y^{(4)}-(gy’)’=\lambda^2y$, where
$g\in C^1[0,a]$ and $a>0$, occur
in engineering on stability of elastic rods. They occur as well in
aeronautics to describe the stability of a flexible missile. Fourth
order Birkhoff regular problems with the differential equation
$y^{(4)}-(gy’)’=\lambda^2y$ and eigenvalue
dependent boundary conditions are considered. These problems have
quadratic operator representations with non self-adjoint operators. The
first four terms of the asymptotics of the eigenvalues of the problems
as well as those of the eigenvalues of the problem describing the
stability of a flexible missile are evaluated explicitly.
Derivation and assessment of a sex-specific fetal growth standard: secondary analysis of a prospective observational study
Authors: Blue Nathan , Allshouse Amanda , Heerboth Sarah , grobman william , Mercer Brian , Shanks Anthony , Bregand-White Julia , Simhan Hyagriv , Reddy Uma , Saade George , Parry Samuel , (USA) Robert Silver
Published: January 2024

Objective: To derive and test the implications of a sex-specific fetal
growth standard. Design: Secondary analysis of a prospective
observational cohort. Setting: Eight U.S. centers. Population or Sample:
Nulliparas followed longitudinally through pregnancy. A lower-risk
subgroup (exclusions: chronic hypertension, pre-gestational diabetes,
suspected aneuploidy, preterm delivery) was selected for fetal growth
equation derivation. Methods: Fetal weights at 14-20 weeks, 22-29 weeks,
and birth were used to derive a sex-specific fetal growth equation. We
compared rates of SGA and LGA by sex using the sex-specific and
sex-neutral (Hadlock) standards. Using the full unselected cohort, we
assessed outcomes and clinical management according to SGA and LGA
status. Main outcome measures: Proportion considered SGA and LGA;
obstetric interventions relevant to SGA and LGA. Results: We derived a
sex-specific equation using 7,280 infants. The sex-neutral standard
diagnosed SGA more often in female and LGA more often in male newborns.
The sex-specific standard resolved these disparities. Using the full
unselected cohort (N=8,339), newborns reclassified from SGA to AGA by
the sex-specific standard were more likely to be delivered for growth
restriction with comparable risk of morbidity compared to newborns
considered AGA by both methods. Newborns reclassified from AGA to LGA by
the sex-specific standard had higher rates of cesarean for arrest of
descent, cesarean for arrest of dilation, and shoulder dystocia than
newborns considered AGA by both methods. Conclusions: The sex-neutral
standard generates sex disparities in SGA and LGA at birth. A
sex-specific standard resolves these disparities and may improve growth
pathology risk stratification.
Remote care and triage of obstetric patients with COVID-19 in the community: operational considerations.
Authors: Bircher Charles , Wilkes Matt , Zahradka Nicole , Wells Emily , Prosser-Snelling Edward
Published: January 2024

We outline the operational model and outcomes of a successful Maternity
Virtual Ward (MVW) established during the SARS-CoV-2 pandemic. Between
October 2021 and February 2022, 429 patients were referred, of which 228
were admitted to the MVW. Total bed-days was 1,182, mean length of stay
was 6 days (SD 2.3, range 1-14 days). Fifteen (6.6%) required hospital
admission and one (0.4%) critical care. There were no deaths. Patients
alluded to increased safety, comfort, and ease with the technology.
Attention should be given to identifying clinical champions, triage
criteria, technology selection, and flexible escalation pathways,
adaptable to changing patterns of disease.
Progression of atherosclerosis in the grafts using for coronary artery bypass: Non-functional high-density lipoprotein and overexpression of LOX-1?
Authors: Arslantürk Oğuz , Aydin Ahmet , Gumus Fatih , Saydam Onur , Aydın Kubra S. , Zeybek Dilara , Canpınar Hande , Guvener Murat
Published: January 2024

Abstract Objectives: We aimed to
investigate the the role of non-functional High-Density Lipoprotein
(HDL) in the form of binding to Lectin-like oxidized low-density
lipoprotein receptor-1 (LOX-1) in patients with Coronary Artery Disaese
(CAD) regarding to progression of atherosclerosis.  Methods: Twenty-one patients who underwent multivessel CABG
using internal mammarian artery (IMA), radial artery (RA) and saphaneous
vein (SV) grafts between November 2019 and April 2020 were obtained.
Using CD31 to identify endothelial cells; LOX-1 expression in all cells
in culture was evaluated.  Findings: The study
consists of 21 patients, 17 (80.9%) males and 4 (19.04%) females.  We
found a significant positive correlation between HDL and LOX-1+ in the
specimens explanted from any type of grafts (SV, r=0.60; RA, r=0.48;
IMA, r=0.53). ~28% of variation in LOX-1+ for IMA
(F=7.03; p<0.05), ~36% of variation in LOX-1+
for SV (F=10.10; p<0.05) and ~24% of
variation in LOX-1+ in the RA (F=5.64; p<0.05) were explained
by HDL.  Conclusions:   In cases with high LOX-1
receptor expression, HDL binds to LOX-1 and loses its function.
Assessment and monitoring of HDL and LOX-1 may help physicians to
predict which patients may be harder to treat and allowing for
appropriate intervention.         Keywords: Atherosclerosis,
Coronary artery bypass grafts, Cardiovascular disease, LOX-1,
Lipoprotein.
Formidable forme fruste of long QT syndrome in a 24 year old female with an eating disorder
Authors: Garapati Sita Sai
Published: January 2024

Long QT syndrome (LQTS) is a myocardial repolarization disorder
characterised by a prolonged QT interval ( >470
milliseconds for men and >480 milliseconds for women) on
the electrocardiogram . It can be congenital or
acquired. Due to the incomplete penetrance and variable expressivity of
genes, this classification is not binary and hence confers different
risks. Acquired LQTS may represent a forme fruste of previously
clinically concealed congenital LQTS. Eating disorders affect 9% of the
population worldwide and carry with them one of the
highest mortality rate of any other psychiatric disorder (second to
opioid overdose) . Women have a 8.4% prevalence of
weighted means for lifetime eating disorders, compared to 2.2% in men
. Since the pandemic began, there has been a surge in
eating disorders according to the national eating disorders association.
Most of these are due to sudden cardiac arrest due to arrhythmias
or suicide. Multiple factors could prolong the QT
interval in such conditions, predisposing patients to malignant
ventricular arrhythmias like torsade de pointes. In eating disorders,
electrolyte abnormalities (hypokalemia and hypomagnesemia) can be caused
due to restrictive eating, purging/ self induced vomiting, refeeding
syndrome, laxative and diuretic abuse. Many antidepressant medications
used in treatment of the same could also cause QT prolongation. Patients
with severe eating disorders may also experience thiamine deficiency or
ipecac induced cardiomyopathy , which could increase
the risk of fatal arrhythmias. If an inherited predisposition for LQTS
is present, it becomes diagnostically apparent when exposed to multiple
inciting factors like these and could manifest in a lethal way.
Characterization of the growth dynamics of holostemparasitic Cuscuta species in the absence of hosts
Authors: Zawaira Alexander , Chen Luxi , Zhou Li , Bessonov Nikolay , Volpert Vitaly , Li Junmin
Published: January 2024

1. Cuscuta species are rootless, leafless and branchless stems without
meaningful photosynthesis. Hence, sink-free and source-free mechanistic
growth models are possible yet remain unexplored. Furthermore,
phytohormone expression has not yet been studied in the absence of
hosts. 2. We use mass conservation in second-order differential
equations to build mechanistic models for Cuscuta growth dynamics and
UPLC-MS/MS to identify and mathematically score phytohormone expression.
3. We identified four sequential stages of growth – exponential,
linear, parabolic deceleration and terminal stages and, in Cuscuta
chinensis, the phases are discernable by eye. 4. Analytical solutions to
the differential equations fit the growth data well and the model also
predicts faster growth in Cuscuta species with smaller seeds, in
agreement with the fact that Cuscuta chinensis attains terminal stage
faster than Cuscuta japonica. 5. We found evidence for stage-specific
phytohormone expression and for the existence of stem-wide phytohormone
gradients, especially for the Auxin components MEIAA and ICAId in
Cuscuta japonica. 6. We have built models for the roles of phytohormones
in Cuscuta growth dynamics, and performed ad hoc calculations which
suggest a continuously-increasing Cytokinin/Auxin ratio in growing
Cuscuta seedlings, thereby implying a maximum value beyond-which growth
slow-down begins. 7. Synthesis: We have created the first-ever
source-free and sink-free plant growth models using mass conservation in
second-order differential equations and in so-doing, uncovered four
growth stages in Cuscuta, observable by eye in Cuscuta chinensis. We
found stage-specific phytohormone expression and a likelihood of
stem-wide phytohormone expression gradients. We then brought it all
together by building models for the roles of phytohormones in Cuscuta
growth dynamics and by performing ad hoc calculations which have
suggested that the Cytokinin to Auxin ratio increases continuously in
growing Cuscuta seedlings, to perhaps attain a maximum value
beyond-which slow-down in growth begins.
A novel SLC26A9 inhibitor, S9-A13, reveals a minor contribution of SLC26A9 to constitutive airway chloride secretion
Authors: Jo Sungwoo , Centeio Raquel , Park Jinhong , Ousingsawat Jiraporn , Jeon Dong-kyu , Talbi Khaoula , Schreiber Rainer , Ryu Kunhi , Namkung Wan , Kunzelmann Karl
Published: January 2024

Background and purpose: The solute carrier 26 family member A9 (SLC26A9)
is an epithelial anion transporter that is assumed to contribute to
basal airway chloride conductance and airway surface hydration. It is a
genetic modifier in cystic fibrosis and therefore may serve as a
possible alternative Cl- secretory pathway in airways. Whether SLC26A9
or CFTR is responsible for airway Cl- transport under basal conditions,
is still unclear, due to the lack of a specific inhibitor for SLC26A9.
Experimental approach: In the present study we report a novel potent and
specific inhibitor for SLC26A9, which was identified by screening of a
drug-like small molecule library and subsequent chemical modifications.
Key results: The most potent compound S9-A13 inhibited SLC26A9 with an
IC50 of 90.9  13.4 nM in YFP fluorescence quenching assay. Notably,
S9-A13 did not inhibit other members of the SLC26-family and showed
little effects on other Cl- channels such as CFTR, TMEM16A, and VRAC.
Although S9-A13 clearly inhibited SLC26A9 when overexpressed in HEK293
cells, it showed little inhibitory effects on ion transport in highly
differentiated human airway epithelial cells or mouse trachea under
basal conditions, despite clear apical expression of SLC26A9 in ciliated
epithelial cells. Conclusions and Implications: Using the potent
inhibitor S9-A13, the present data demonstrate the lack of activity of
SLC26A9 in nonstimulated airways. Because on the contrary, the
CFTR-inhibitor CFTRinh-172 clearly inhibited transport in non-stimulated
airways, we conclude that CFTR rather than SLC26A9 is in charge of
constitutive Cl- transport in airways.
Frontal Lobe Development in Fetuses with Growth Restriction: A Case-Control Study
Authors: Peng Ruan , Zheng Qiao , Wu LiHong , Zheng Ju , Yin Xia , Xie HongNing
Published: January 2024

Objective: To evaluate the impact of fetal circulatory redistribution
(FCR) on frontal lobe development in fetuses with growth restriction
(FGR) compared with appropriately grown fetuses. Design: Case-control
study Setting: A referral center from August 2020 to July 2021.
Population/Sample: 324 appropriately grown fetuses were included to
establish Z-score reference ranges for frontal antero-posterior diameter
(FAPD) and occipito-frontal diameter (OFD). The case-control analyses
included 55 with FGR and 220 gestational age and fetal sex-matched
appropriately grown fetuses. Methods: FAPD and OFD were measured on
trans-ventricle view in FGR and appropriately grown fetuses. Main
Outcome Measures: We calculated Z-scores for FAPD and OFD in
appropriately grown fetuses. To compare intracranial parameters, we
randomly selected a control group of appropriately grown fetuses matched
with the FGR group at ultrasonography. We performed between-group
comparisons of FAPD Z-score, OFD Z-score, and FAPD/OFD ratio. Results:
All independent variables (GA, BPD, FL, and TCD) were strongly
correlated with FAPD and OFD. FAPD/OFD ratio was curvilinear related to
all the independent variables (GA, BPD, FL, and TCD). Compared with
appropriately grown fetuses, fetuses with FGR showed a significantly
lower FAPD/OFD ratio and FAPD Z-score. There was no significant
difference in the FAPD Z-score and FAPD/OFD ratio between fetuses with
FGR with and without FCR. Conclusions: The FAPD/OFD ratio slightly
varied during pregnancy, with a small reduction before and an increase
after about 33 gestational weeks. Fetuses with FGR showed impaired
frontal lobe growth; moreover, fetal frontal lobe development disorders
were not significantly different in FGR with FCR.
An open-source topology optimization modeling framework for the design of passive micromixer structure
Authors: Na Jian , Li Hong , Yan Peng , Li Xingang , Gao Xin
Published: January 2024

In the microfluidic systems, the structure of micromixer is one of the
important influence factors for the mixing performance. The traditional
trial-and-error method for the optimization design of micromixer
structure is difficult to consider both the mixing performance and power
dissipation. Here we show the topology optimization method of designing
the passive micromixer with the minimum power dissipation. The
micromixer structure is updated with the adjoint method and adjoint
variables are solved by the continuous adjoint equation derived
manually. The forward fluid problem and adjoint equation are constructed
using OpenFOAM. The optimal structure of micromixer is generated at
different mixing index constraint and Re in two-dimensional design
problem. Furthermore, in the three-dimensional optimal design, the
multiple spiral slice structures are produced along the micromixer,
which generate chaotic advection. This open-source topology optimization
modeling framework is effective to design optimal structure of
micromixer.