bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Knowledge Regarding Furcation Defects among Dental Practitioners: A Multinational Survey
Authors: Gummaluri Shiva Shankar , KK Shivalingesh , Sharma Swati , Manjunath R G Shiva , Shrestha Riya Duwal , Panguluri Thanmayi
Published: January 2024

This study was undertaken to assess knowledge regarding furcation defects among dental fraternity. This is an open-ended, randomized, web-based cross-sectional multinational online survey. A total of 904 responses were gathered by sending 13 questions through a google form. Data were expressed in frequency and percentages. Chi-square test was performed to determine significant difference between gender, education level and variation between dentists of India and other countries. P value <0.05 was considered to be statistically significant. Present study had 650 dentists from India and 254 dentists from other countries. For overall knowledge regarding furcation, 90.7% (average of first and second question) of dentists had knowledge regarding furcation. There was no significant difference between males (range 54%-93%) and females (range 46%- 95%) (p>0.05) in terms of knowledge. Majority (88.7%) of post-graduates knew about the use of Nabers probe for furcation measurements and values were significant (p<0.05). Present study also revealed 65%-67% of undergraduates and post-graduates knew that Degree II furcation defects showed predictable periodontal regeneration, however values were non-significant (p>0.05). There was no statistical significance (p>0.05) between dentists of India and other countries. Dental fraternity in general had adequate knowledge regarding the furcation defects, their treatment modalities and expected complications.
The optimal control for time-fractional non-Newtonian fluid equations
Authors: Shao Guangming
Published: January 2024

This paper is concerned with the non-Newtonian fluid equations with the
time-fractional derivative of the order
$\alpha\in(0,1)$. We first establish
existence criterion of weak solutions in the case that the dimension
$n=2$ by dint of the classical Faedo-Galerkin approximations method.
Then we prove the sufficient condition of optimal pairs.
Global existence and blowup of solutions of quasilinear fractional reaction-diffusion equation with singular potential
Authors: Li Jianjun , Wang Kankan
Published: January 2024

In this paper, we consider the quasilinear fractional reaction-diffusion
equation with singular potential the existence, decay estimate and long
time asymptotic behavior of the global solution and the blowup behavior
of the solution are discussed. Because of the non-locality of fractional
Laplacian operator, the Caffarelli-Silvestre extension method is used to
transform the nonlocal problem into an elliptic problem with dynamic
boundary conditions. Firstly, the global existence of the solution is
proved under appropriate assumptions, and on this basis, the decay
estimate and long time asymptotic behavior of the global solution and
the blow-up behavior of the local solution are obtained by using the
potential well methods.
Genome-wide association study identifies variants of GhSAD1 conferring chilling tolerance in cotton
Authors: Ge Chang , Wang Li , Yang Yong , Liu Rui , Li Shi , Liu Shao , Chen Jing , Shen Qian , Ma Hui , Li Yang , Zhang Si , Pang Chao
Published: January 2024

Cold stress is a major environmental factor affecting plant growth and
development. Although some plants have developed resistance to cold
stress, the molecular mechanism underlying it is poorly understood.
Therefore, the aim of this study was to identify genes conferring cold
resistance in cotton. Here, we identified cold tolerance gene in cotton
(Gossypium hirsutum L.) using genome-wide association study
(GWAS) with 200 cotton accessions collected from different regions. A
variant of the gene was also identified. The results of the study showed
that GhSAD1 improved cold-stress resistance
in cotton by increasing abscisic aldehyde (ABAld) and amino acid
contents under chilling stress conditions.
GhSAD1 introduction considerably increased
chilling tolerance in Arabidopsis transgenic plants, whereas
GhSAD1 plants exhibited chilling-sensitive
phenotype. Additionally, we found that
GhSAD1 regulated chilling stress responses
in cotton through the activity of c-repeat binding factor, which binds
to the promoter region of the gene and regulates the ABA signalling
pathway under chilling conditions. Overexpression of
GhSAD1 induced COR genes expression
and improved metabolic profile under cold stress. Collectively, the
findings of the study contribute to our understanding of the underlying
mechanism of GhSAD1 in cold-stress response in cotton. Moreover,
GhSAD1 could serve as candidate gene in improving crop stress.
Host population-connectivity is a major influencer of the genetic structure of Theileria annulate
Authors: Babiker Hamza , Al-Hamidhi Salama , Parveen Asia , Iqbal Furhan , Asif Muhammad , Akhtar Naheed , Elshafie Elshafie I. , Beja-Pereira Albano
Published: January 2024

The genetic structure of parasites is expected to mirror that of their
hosts, as host dispersal is the primary driver to parasite spread.
Theileria ( T.) annulata is a tick-borne protozoan
parasite that is responsible for bovine theileriosis worldwide. The
present study examined analyzed a set of specific micro/mini-satellites
and the genetic structure of T. annulata in cattle breeds from
Pakistan (Indian sub-continent) compared to that in Oman (Middle East),
Tunisia (Africa) and Turkey (Europe). A high level of genetic diversity
was observed among T. annulata detected in cattle from Pakistan
comparable to that in Oman, Tunisia, and Turkey. T. annulata
genotypes from these four countries form genetically distinct groups
that are geographically sub-structured and this trend is correlated with
geographical distance between these countries. The parasite population
in Oman overlapped with that the T. annulata population in Africa
and the Indian Subcontinent. The observed pattern of genetic
differentiation of T. annulata accords well with that seen among
cattle breeds in the Near East - European (Turkey), African (Libya), the
Indian-Subcontinent (India) and the Arabian Peninsula. In conclusion, we
are reporting dispersal of host affects the genetic structure of
T. annulata.
Crossing Our T’s: An Unusual Presentation of Infantile T-cell Leukemia
Authors: Rahim Mahvish , Colace Susan , Belsky Jennifer
Published: January 2024

T-Cell Acute Lymphoblastic Leukemia (T-ALL) is commonly diagnosed in
adolescents and is a rare diagnosis in children under 12 months of age.
There is little guidance regarding the details of management and
outcomes for infantile T-ALL, in particular the use of nelarabine in an
infant. Additionally, the genomic landscape of this rare oncologic
presentation has not been well documented. We present the unique
management, genomics, outcomes, and clinical course of a patient with
the diagnosis of infantile T-ALL.
An unusual case of chronic and reversable pulmonary hypertension
Authors: Suárez Paola del Coromoto Leon , Larrinoa Iñigo Rúa-Figueroa Fernández de , Urso Stefano , Esmenota Jose Domingo Marín , Nogales Eliú , Portela Francisco
Published: January 2024

Behcet’s Disease (BD) is currently classified as “variable vessel
vasculitis” (Chapel Hill, 2012). It is a chronic, multisystemic,
inflammatory rheumatic disease. Its main manifestations are
mucocutaneous, neurological, cardiovascular, pulmonary and
musculoskeletal. Vascular involvement of BD, so-called “angio-Behcet”,
appears in 7%-29% of patients. Arterial complications, such as
arterial stenoses, pseudoaneurysms, and ruptures occur in a 1-14% range
and represent a major cause of morbidity and mortality in BD patients.
We, herein, report the case of a large aortic pseudoaneurysm producing
severe pulmonary hypertension in a patient with angio-Behcet who had
previously undergone aortic root replacement.
Impaired T lymphocyte subsets early predict acute kidney injury in sepsis patients
Authors: Li Guanglan , Zhang Yu , He Ganyuan , Hao Wenke , Hu Wenxue
Published: January 2024

Objective: Acute kidney injury (AKI) is a frequent complication of
sepsis patients and is associated with high morbidity and mortality.
Early recognition of sepsis-associated AKI (SA-AKI) is crucial to
provide supportive treatment and improve prognosis. Thus, the objective
is to analyze the early discriminative predictive information regarding
T lymphocyte subsets of SA-AKI. Methods: We evaluated the relationships
of T lymphocyte subsets and clinical parameters of sepsis patients, and
assessed their potential roles in SA-AKI diagnosis. The following T
lymphocyte subsets were studied: total T lymphocyte (CD3+), helper T
lymphocyte (T helper, CD3+CD4+), cytotoxic T lymphocyte (CTL, CD3+CD8+),
totally activated T lymphocyte (CD3+HLADR+), early activated T
lymphocyte (CD4+CD69+, CD8+CD69+), regulatory T lymphocyte (Treg,
CD4+CD25+, CD8+CD25+). Results: A total of 171 patients with sepsis were
enrolled. The incidence of AKI was 80.1%. The percentages of total T
lymphocyte, CTL, and totally activated T lymphocyte of SA-AKI patients
were lower than those in non-SA-AKI patients. There were no significant
differences in the percentages of T helper, early activated T
lymphocyte, and Tregs between SA-AKI group and non-SA-AKI group.
Univariate logistic regression analysis showed percentages of total T
lymphocyte, CTL, and totally activated T lymphocyte were protective
factors for SA-AKI. Multivariate logistic regression analysis revealed
percentage of totally activated T lymphocyte had a negative association
with SA-AKI independently. Moreover, ROC analysis showed that total T
lymphocyte, CTL, and totally activated T lymphocyte had discriminatory
abilities. Conclusions: Impaired total T lymphocyte, CTL, and totally
activated T lymphocyte could contribute to early diagnosis for SA-AKI.
Atrial proarrhythmias of ivabradine by inducing intracellular calcium overload and delayed afterdepolarizations in rabbit heart
Authors: Wang Chengyu , Lin Mingjie , Yang Qiaomei , Li Gang , Liu Xiaoyan , Zhang Qing , Yu Shandong , Wu Lin
Published: January 2024

Background: Ivabradine (IVA) inhibits
hyperpolarization-activated cyclic nucleotide channel to reduce pacing
current with a possible increasing risk of atrial fibrillation (AF).
Objective: To determine the effects of IVA on atrial action
potentials, atrial arrhythmic activities and intracellular calcium
homeostasis. Methods: Langendorff-perfused hearts and atrial
myocytes from New Zealand White rabbits were used to record 12-lead
ECGs，left atrial monophasic APs and Ca sparks.
Ca handing related protein from left atrium were
tested using western blotting. Results: IVA (0.1-10 μM) slowed
the HR and prolonged the atrial MAPD (n=8,
p<0.05) and induced atrial arrhythmias in 26% and 77% of
hearts paced at cycle lengths of 350 ms and 570 ms, respectively (n=23
and 13, p<0.05). In hearts treated with either 0.3 µM
acetylcholine (ACh) or 2 nM ATX-II with modulated atrial MAPDs, IVA
(0.1-10 µM) caused either shortening or prolongation of
MAPD, respectively (n=18 and 21, p<0.05) and
atrial arrhythmias in 61.9% and 44.4% of hearts (p<0.05).
IVA induced delayed afterdepolarizations in 41.7%, 62.5% and 50% of
cells in the absence and presence of either ATX-II or ACh, respectively
(n=12, 8 and 8, p<0.05). IVA (0.03-3 μM) increased the
frequency, amplitude and full width at half-maximum (n=22,
p<0.05), and the expression of ryanodine receptor and
Na/Ca exchanger with decreased
sarcoplasmic reticulum calcium pump (n=4-5, p<0.05).
Conclusion: IVA caused a blunted HR reduction and increased
atrial proarrhythmic risk in hearts with slow rate, enhanced vagal tone
and late I, and DADs resulting from enhanced
Ca release.
A Quality Improvement Initiative: Routine End of Therapy Bone Marrow Aspirates in Pediatric B cell Acute Lymphoblastic Leukemia in Oman
Authors: Mughairy Alyaa Al , Khan Shadhiya Al , Al-Ghaithi Ibrahim , Williams Suzan
Published: January 2024

The utility of end of treatment bone marrow aspirates (EOTBMA) and
cerebral spinal fluid analysis (EOTCSF) in B-cell acute lymphoblastic
leukemia (B-ALL) is unclear. A retrospective review, n=50, B-ALL age
1-18 years at diagnosis, having EOTBMA and EOTCSF, at a single
institution 2010-2018 was conducted. No bone marrow or CNS relapse was
detected by EOTBMA or EOTCSF. 4/50 (8.0%) patients relapsed at a median
of 2.5 years (range 0.9-4.5 years). Consensus to abandon routine EOTBMA
occurred by presenting results to faculty. Our data supports absence of
utility of routine EOTBMAs and EOTCSF in pediatric B-ALL. Disseminating
local data facilitated consensus in implementing best practice.
“Likelihood to be diagnosed or misdiagnosed” revisited: the Efficiency Index
Authors: Larner Andrew
Published: January 2024

Objectives: To calculate an “efficiency index” (EI) based on “numbers
needed” metrics (specifically to diagnose and to misdiagnose) for
cognitive screening instruments which are commonly used in suspected
dementia, and to compare these values with those of a previously
described “likelihood to be diagnosed or misdiagnosed” (LDM) metric
also based on “numbers needed” metrics. Methods: Datasets from
pragmatic test accuracy studies examining four brief cognitive screening
instruments (Mini-Mental State Examination, MMSE; Montreal Cognitive
Assessment, MoCA; Mini-Addenbrooke’s Cognitive Examination, MACE;
Free-Cog) were analysed to calculate values for EI and LDM, and to
examine their variation with test cut-off for MACE,. Findings: EI and
LDM had similar values for all the screening instruments examined but EI
was simpler to calculate than LDM. Both metrics showed similar maxima
across a range of cut-offs for MACE. The differing score range of EI and
LDM allowed the former, but not the latter, to be qualitatively
classified as for likelihood ratios, with three of the tests (MMSE,
MACE, Free-Cog) achieving a “moderate” increase in the likelihood of
dementia diagnosis. Conclusions: The efficiency index (EI) metric
indicates the utility or inutility of diagnostic tests in a way that is
easily intelligible for both clinicians and patients, illustrating the
inevitable trade-off between diagnosis and misdiagnosis.
ON THE FRACTIONAL LUCAS DIFFERENCE SEQUENCE SPACES
Authors: Karakas Murat
Published: January 2024

In this article, we compound the fractional order difference operator
with the Lucas matrix and introduce the new difference sequence spaces.
Also, we investigate some topological properties and give Schauder
basis. Finally, we examine the geometric structure of this space.
Genome of the estuarine oyster reveals climate impact and adaptive plasticity
Authors: Li Ao , Dai He , Guo Ximing , Zhang Ziyan , Zhang Kexin , Wang Chaogang , Wang Wei , Chen Hongju , Xuming Li , Zheng Hongkun , Zhang Guofan , LI LI
Published: January 2024

Understanding genomic bases of environmental adaptation is central to
evolutionary biology and important for assessing adaptive potential of
organisms under rapid climate change. Climate change is causing profound
changes in world’s ocean, and genomic studies on keystone marine species
such as the estuarine oyster (Crassostrea ariakensis) may inform
how marine ecosystems respond to environmental shifts. We constructed a
chromosome-level assembly of the estuarine oyster genome that spans
613.89 Mb and encodes 29,631 proteins. Resequencing of 264 wild
individuals across wide latitude distribution revealed remarkably low
genomic diversity in the estuarine oyster compared with its sister
species and fine population structures shaped by historical glaciation,
geological events and oceanographic forces. Genes from regions under
selection were mostly involved in responding to temperature and salinity
stress, demonstrating selection by these two environmental factors is a
strong evolutionary force. Genes under selection included a large
cluster of tandemly duplicated members of the solute carrier membrane
transport protein families which are also expanded in two other
low-salinity oyster species, highlighting the significance of membrane
transporter expansion in estuarine adaptation. Genes exhibiting high
plasticity showed strong selection in upstream regulatory regions that
modulate transcription, indicating selection favoring plasticity. This
study revealed genomic signatures of past glaciation and fine population
structures shaped by climate history, physical forces and selection in a
bivalve mollusc. Our results show gene expansion and selection in
regulatory regions enhance phenotypic plasticity that is critical for
organisms to survive and adapt to rapidly changing environments.
Design of a Long-pass Filter with Effects on Fluorescence Image Observation for Surgical Fluorescence Microscope Applications
Authors: Kim Jinkyu , Yoon Ki-Cheol , Kim Kwang Gi
Published: January 2024

Fluorescein sodium (FL) has been widely used in disease diagnosis and
surgery. It is a yellow-dye that fluoresces when the light at
wavelengths from 400 nm to 490 nm is irradiated, and its fluorescence
can be observed with a surgical fluorescence microscope and a long-pass
filter. However, even if an advanced microscope is used, it fails to
produce a clear fluorescence image. As a result, it is possible that
surgeons are experiencing difficulty in distinguishing tumors from blood
vessels. Thus, this paper investigated the effects of a long-pass filter
on the fluorescence image and discovered characteristics that affect the
quality of the image. In this study, 0.0102mM of FL and a near-infrared
camera were prepared, and the fluorescence was observed both in the
presence and absence of a long-pass filter. By comparing two different
types of the image, it was revealed that a filter is a necessary
component in fluorescence microscopy as it blocks undesired light.
Furthermore, the intensity of fluorescence after passing through a
fabricated filter and a conventional filter was measured. It was
discovered that a filter that transmitted the more light has higher
transmittance (T) and lower power loss (PL) and optical density (OD).
Given that an image becomes clearer if a filter transmits more light, it
was concluded that a filter with higher T and lower PL and OD would
produce a clearer fluorescence image. If this type of a filter is used
in surgery, surgeons will be able to more effectively carry out tumor
resection.
How to Enhance Pharmaceutical Career Readiness during MD Pharmacology?
Authors: Leekha Saikiran , Chaudhari pratishtha
Published: January 2024

The traditional career path from MD Pharmacology to the medical
affairs(MA) within pharmaceutical industry is becoming increasingly
challenging and competitive. The MA role has evolved from a ‘medical-
knowledge-and-support-only’ role to a ‘strategic decision-making,
scientific partner’. Traditional MD Pharmacology background and related
knowledge are essential but may no longer be sufficient to ensure
‘Day-1-preparedness’ for an MA role. Transitioning from a medical
college environment to the corporate environment would become easier if
one develops certain additional soft and hard skills as elaborated in
this article. The objective of this manuscript is to recommend how to
better-equip the MD Pharmacology residents to be a confident,
resourceful and successful MA professionalS. We also elucidate on key
skill gaps and the suggested approaches to invest the residency time
more judiciously to bridge those gaps for developing more industry-ready
pharmacologists. A special segment on changes pertaining to COVID-19
pandemic is also included.
Tetrapeptides targeting the testosterone binding site of ZIP9 stimulate myotube formation in myogenic cells and mineralization in osteogenic cells
Authors: Malviya Viveka , Bulldan Ahmed , Wende Raffael , Möller Marie-Louise , Schreiner Peter , Scheiner-Bobis Georgios
Published: January 2024

Background and Purpose: Pro-androgenic substances are often used to
treat muscle- or bone-related disorders. Their interactions with the
classical androgen receptor (AR), however, trigger a series of
undesirable effects. It would be of great benefit if the positive
androgenic effects could be obtained by circumventing the classical AR.
Experimental Approach: ZIP9 is a recently identified membrane-bound
androgen receptor of physiological significance. Using in silico methods
we identified and verified the extracellular localization of its
androgen binding site and designed small peptides that fit in it without
interacting with the AR. Six tetrapeptides with the best docking
properties were synthesized and further investigated. Key Results: All
tetrapeptides displaced T-BSA-FITC, a membrane-impermeable testosterone
analog, from the surface of mouse myogenic L6 cells that express ZIP9
but not the AR. Silencing the expression of ZIP9 with siRNA prevented
this labeling. All tetrapeptides act pro-androgenic: in L6 cells they
stimulated the expression of myogenin, triggered activation of focal
adhesion kinase, and prompted the fusion of L6 myocytes to syncytial
myotubes. In human osteoblastic SAOS-2 cells that express AR and ZIP9
they reduced the expression of alkaline phosphatase and stimulated
mineralization. These latter effects were prevented by silencing ZIP9
expression, indicating that the osteoblast/osteocyte conversion is
exclusively mediated through ZIP9. Conclusions and Implications: Our
results demonstrate that the synthetic tetrapeptides, by acting as
ZIP9-specific androgens, have the potential to replace testosterone or
testosterone analogs in the treatment of bone- or muscle-related
disorders by circumventing the undesirable effects mediated through the
classical AR.
Human CYSLTR1 and GSDML gene polymorphisms detection kit provides a new idea for individualized treatment of asthma and improvement of prognosis.
Authors: Jin Zheng Shuo , Kong Lingjun  , Pan Zhou-Xian , Zhong Min , Yang Yongshi , Dou Yaling , Sun Jin-Lu
Published: January 2024

Background: Identification of gene polymorphisms and SNP analysis of
individual patients have become crucial to select the best drug response
and ensure optimal care, especially for genes directly related to
asthma, such as CYSLTR1 and GSDML gene polymorphisms, an efficient and
accurate detection method is helpful for the development of precision
therapy. The novel detection kit we used has a reading accuracy of
99.999% for each base and the cost of detection is only 80 minutes.
Objectives: In this study, a novel kit produced by Wuhan healthcare
Biotechnology Co., LTD was used to detect CYSLTR1 and GSDML gene
polymorphisms in asthma patients and the reliability of the novel kit
was verified. Methods: The efficiency of the new kit was validated
compared to gold standard, gene sequencing methods, and the close
association of CYSLTR1 and GSDML SNPs with allergic asthma was also
tested. As a result, the most effective drugs were obtained for patients
with different gene locus expressions. Results: Identifying 367
publication participants for analysis by two different methods, we
validated the reliability of the reagents with “gold standard” assays
in full agreement with the DNA direct sequencing method. Our study
focused on CYSLTR1 and GSDML gene polymorphisms to select the most
effective drugs for asthma treatment, with leukotriene modulators being
more effective in patients with the AA genotype of CYSLTR1 rs320995 and
β2 agonists being more effective in patients with the TC genotype of
CYSLTR1 rs320995.
Automated dander dispersal in a cat Naturalistic Exposure Chamber
Authors: Haya Laura , Mehri Rym , Somers-Neal Shawn , Mosselaer Stefan Van de , Spence Ashley , Kelly Suzanne , Matida Edgar , Yang William
Published: January 2024

Allergen exposure chambers (AEC) provide controlled allergen exposure to
allergic subjects for the clinical study of asthma and allergy. They
should ideally mimic natural allergen exposure, and provide better
control of allergen exposure than possible in field studies. For AEC
exposure to cat allergens, typically, either liquid allergen extract is
nebulized, or natural cat hair and dander are aerosolized by shaking cat
bedding. While bedding shaking is more naturalistic than liquid extract
exposure, it results in high variability of allergen levels. We have
developed an automated method of natural dander dispersal that uses
robotic vacuum cleaners with filters removed and modified for variable
suction. The system was validated in two rooms (14.4 m3 and 36.7 m3)
where two cats reside. The vacuums aerosolize aspirated dander that has
naturally accumulated on the floor. Dispersion was characterized by
measured airborne allergen (Fel d 1) and particle sizes and
concentrations in time and space during 1 and 2-hour tests. At optimized
parameters, Fel d 1 was found to be stable in time (2 hours), and
homogenous throughout the rooms. Average Fel d 1 was 55 (±9 SD) ng/m3 in
the smaller room and 79 (±30 SD) ng/m3 in the larger room, which are
comparable to exposure in homes with cats. This novel method of dander
dispersal provides controlled, safe exposure to cat allergens in a
clinical setting, while maintaining the naturalistic advantages of a
field exposure.
Mediators Linking Obesity to Childhood Asthma: the Role of Puberty, Physical Fitness, and Pulmonary Function
Authors: Chen Yang-Ching , Su Ming-Wei , Pan Wen-Harn , Lee Yungling
Published: January 2024

Background: Obesity and asthma are highly associated, but the mechanisms
underlying the association remain unknown. We examined five mediators
linking obesity with childhood asthma: (1) pulmonary function
impairment, (2) airway inflammation, (3) physical fitness, (4)
sleep-disordered breathing (SDB), and (5) early puberty. Methods: A
Mendelian randomization (MR) study with mediation analysis of data
obtained from 5,965 children as part of the Taiwan Children Health
Study. Cross-sectional regression analysis, MR two-stage least squares
method, and MR sensitivity analysis were carried out to investigate each
causal pathway. Prospective cohort analyses were used to confirm the
findings. Results: The increased asthma risk associated with obesity was
found to be mostly mediated through impaired pulmonary function, low
physical fitness, early puberty. In the MR analysis, body mass index was
negatively associated with FEV1/FVC and physical fitness index (β= −2.17
and −0.71; 95% CI, −3.92 to −0.42 and −1.30 to −0.13, respectively) and
positively associated with early puberty (OR, 1.09; 95% CI,
1.02–1.17). High FEV1/FVC and physical fitness index reduced the risk
of asthma (OR, 0.98 and 0.93; 95% CI, 0.97–0.99 and 0.88–0.98,
respectively), whereas SDB and early puberty increased the risk of
asthma (OR, 1.03 and 1.22; 95% CI, 1.01–1.05 and 1.05–1.42,
respectively). The three main mediators were low physical fitness,
impaired pulmonary function, and early puberty, with mediation
proportions of 91.4%, 61.6%, and 28.3%, respectively. Temporal
causality was further strengthened in prospective cohort analyses.
Conclusions: Interventions promoting physical fitness and pulmonary
function might effectively reduce obesity-induced asthma risk.
Impact of SARS-CoV-2 infection (COVID-19) on cytochromes P450 activity assessed by the Geneva cocktail.
Authors: Lenoir Camille , Terrier Jean , Gloor Yvonne , Curtin François , Rollason Victoria , Desmeules Jules , Daali Youssef , Reny Jean-Luc , Samer Caroline
Published: January 2024

Background and purpose Coronavirus Disease 2019 (COVID-19), caused by
SARS-CoV-2 infection, is a severe acute respiratory syndrome with an
underlying inflammatory state. We have previously demonstrated that
acute inflammation modulates cytochromes P450 (CYP) activities in an
isoform-specific manner. We therefore hypothesized that COVID-19 might
also impact CYP activities, and thus aimed to evaluate the impact of
acute inflammation in the context of SARS-CoV-2 infection on the six
main human CYPs activity. Experimental Approach This prospective
observational study was conducted in 28 patients hospitalized at the
Geneva University Hospitals (Switzerland) with a diagnosis of moderate
to severe COVID-19. They received the Geneva phenotyping cocktail orally
during the first 72h of hospitalization and after three months.
Capillary blood samples were collected 2h after cocktail administration
to assess the metabolic ratios (MRs) of CYP1A2, 2B6, 2C9, 2C19, 2D6 and
3A. CRP, IL-6 and TNF-α levels were also measured in blood. Key Results
CYP1A2, CYP2C19, and CYP3A MRs decreased by 52.6% (p=0.0001), 74.7%
(p=0.0006) and 22.8% (p=0.045), respectively, in COVID-19 patients.
CYP2B6 and CYP2C9 MRs increased by 101.1% (p=0.009) and 55.8%
(p=0.0006) respectively. CYP2D6 MRs variation did not reach statistical
significance (p=0.072). As expected, COVID-19 was a good acute
inflammation model as mean serum levels of CRP, IL-6 and TNF-α were
significantly (p<0.001) higher during SARS-CoV-2 infection.
Conclusion and implications CYP activities are modulated in an
isoform-specific manner by SARS-CoV-2 infection. The pharmacokinetics of
CYP substrates, whether used to treat the disease or as the usual
treatment of patients, could be therefore clinically impacted.
Translocator protein ligand Ro5-4864 promotes melanogenesis in a TSPO independent manner
Authors: Yue Yunyun , Liao Zi-xian , Wang Yi-chuan , Liu Qiu-yan , Dong Jing , Zhong Min , Chen Ming-han , Pan Yu-min , Zhong Hui , Shang Jing
Published: January 2024

The 18-kDa translocator protein (TSPO) is highly conserved among
different species but with perplexing biochemical function. Multiple
ligands of TSPO show commendable regulatory activities among lots of
biological functions, such as neuroinflammation, cholesterol transport
and so on. These researches support that TSPO may be a potential target
for disease treatment and drug development. Previous studies have shown
that its ligand agonist benzodiazepines have the effect of promoting
melanin, but the specific mechanism is still unclear. In this research,
we firstly confirmed the melanogenesis promotion of Ro5-4864 in mouse
melanoma cell line, human skin tissue and zebrafish embryos through
inducing melanin synthesis and melanosome transport. Molecular genetics
and pharmacological studies showed that TSPO deficiency did not affect
melanin production in B16F10 cells and zebrafish embryos, nor did it
affect melanin promotion effect of Ro5-4864. The expression of lots of
melanogenesis related proteins, such as TYR, TRP-1, DCT, Mlph and Rab27
were upregulated in Ro5-4864 treatment cell with or without Tspo. These
results indicated that Ro5-4864 induced melanogenesis in a TSPO
independent manner. However, further research is still needed to clarify
the direct downstream target of Ro5-4864 in promoting melanogenesis.
PREVALENCE, RISK FACTORS, PHARMACOEPIDEMIOLOGY AND INNOVATIONS PREVENTION OF BRONCHIAL ASTHMA
Authors: Ganiev Bakhtiyor
Published: January 2024

Background: Industrial chemical compounds are also included in the list
of causative factors of bronchial asthma. The contribution of industrial
allergens to the formation of bronchial asthma is undeniable. The paper
considers the degree of knowledge of the prevalence and risk factors for
the formation of bronchial asthma to give a reasonable assessment of
domestic and foreign researchers’ published works to draw logical
conclusions from the research done. It helps to predetermine more
relevance of studying pharmacoepidemiology, measures prevention.
Methods: A stratified random sample design was used in this study,
including custom-designed questionnaires. Two sets of surveys were used
to identify asthma-like symptoms, which were then validated by
respiratory physicians using a pulmonary function test and bronchial
dilation test. Results: In studies carried out in conjunction with
professional pathologists, children were found to be sensitized to
industrial allergens (nickel, chromium, formaldehyde, etc.), which
contribute to the formation of bronchial asthma. Determining, however,
is the presence of atopy. Conclusions: Today the prevalence of BA is a
serious problem, not only from a medical but also from the social and
economic point of view. Many primary prevention strategies did not show
in randomized clinical trials sufficient proofs so that they were used
in clinical practice. Preventive interventions need to be taken to
reduce the disease burden at the community level. It will predetermine
further relevance of studying pharmacoepidemiology and measures for
primary secondary, and tertiary prevention of this disease.
Scar cosmesis in major head and neck operations: a systematic review of skin closure techniques
Authors: Williamson Andrew , Connelly Andrew , Awad Zaid
Published: January 2024

Background: The cosmetic appearance of head and neck surgical scars can
have a major impact on body image and quality of life. Numerous wound
closure methods such as staples, sutures, adhesives and surgical tape
are available, and our aim is to investigate whether one closure method
offers superior cosmetic outcomes over the others. Objectives: The
primary outcome was patient and clinician reported cosmetic appearance.
Secondary outcome measures such as post-operative complications were
also measured. Design: A systematic review was undertaken of Pubmed, Web
of Science and the Cochrane database. Searches were performed using the
MeSH terms “tissue adhesives”, “wound closure techniques”,
“surgical tape” and “sutures”, combined with various head and neck
operations using Boolean operators. Results: The initial search found
2753 papers, of which 2,721 were excluded after removal of duplicates
and screening. 32 papers underwent full text review and 7 were included
in the review. The studies did not show any significant difference in
cosmesis or wound complications. Surgical staples and tissue adhesives
had significantly shorter wound closure time than sutures. No studies
reported on head and neck scar’s impact on quality of life or body
image. Conclusions: From the studies presented here, there is no
significant difference in short term wound cosmesis using tissue
adhesives, sutures, or surgical staples. However, the papers included
are generally of poor quality and contained a moderate to high risk of
bias, and thus further studies are needed to establish the cosmetic and
quality of life impact of varying wound closure techniques following
head and neck surgery.
DEPOLYMERIZATION OF LIGNIN BY EXTRACELLULAR ACTIVITY OF PYCNOPORUS CINNABARINUS, TO OBTAIN CELLULOSE
Authors: Brambila Margarita M. , Guzmán-Gi Raymundo , Velasco-Bedrán Hugo , González-Brambila Oscar
Published: January 2024

A biotechnological process for cellulose recovery from cactus waste
through depolymerization of lignin by Pycnoporus cinnabarinus, is
presented. The delignification is carried out by fermentation in a batch
stirred bioreactor, with a culture medium enriched with nutrients and
minerals without added carbon sources, during a six-day span under
continuous feeding of oxygen. A factorial design of experiments (DOE)
for eight sets of factor values was selected for this study. The factors
were: particle size, pH level, and process temperature. For each
experiment, biomass, total reducing carbohydrates, and dissolved oxygen
concentrations were measured every 24 hours. At the end of each
experiment, the percentage of delignification, and cellulose recovery
was measured by Infrared (IR) spectroscopy. Up to 67% of
delignification and 22% of cellulose recovery were obtained by the
process. These results were analyzed by a factorial DOE in order to
maximize each response individually and to optimize both responses
together. The delignification of Opuntia ficus indica thorns has not
been previously reported to our knowledge.
Anti-Glutamic Acid Decarboxylase Auto Antibody associated neurological disorder in patients with Acute lymphoblastic leukemia treated with standard protocol
Authors: Vasileva Alisa , Popescu Marcela
Published: January 2024

Objective: To report two cases with anti-GAD antibodies associated
neurological disorder in patients with acute leukemia who received
standard chemotherapeutic protocols. Clinical presentation and
intervention: Case 1: patient with biphenotypic acute leukemia developed
motor neurological symptoms while receiving induction therapy. Anti-GAD
antibodies were demonstrable in the CSF and serum, and the patient
responded to Intravenous Immunoglobulin (IVIG) therapy. Case 2: Patient
with relapsed B-Acute lymphoblastic leukemia (ALL) after allogenic stem
cell transplant developed progressive neurological symptoms. Anti-GAD65
antibodies were demonstrable in the serum, but not the CSF. The patient
did not respond to IVIG and had to be given plasmapheresis and steroids.
2-year follow-up status of both patients is provided. Conclusion:
Immunological etiology with Anti-GAD antibodies needs to be considered
in the differential diagnosis of central and peripheral neurological
illness in acute leukemia patients on standard chemotherapeutic
protocol. IVIG is an effective treatment for this condition. However, in
case of inadequate or no response, plasmapheresis with steroid or
rituximab should be considered. Long-term management is required to
prevent and manage relapse of autoimmune neurological illness.
Pharmacovigilance regulatory actions by National Pharmacovigilance centres in fourteen Middle Eastern Countries following COVID-19 Pandemic
Authors: Al-Zubiedi Sameh , Younus Manal , AL-Khalidi Sara , Ekelo Magnus , Alshammari Thamir
Published: January 2024

Background. Globally, pharmacovigilance activities were affected by
COVID-19. Therefore, several competent health authorities around the
world, including several countries in the Middle East, have issued
guidelines and practices to ensure that pharmacovigilance activities are
maintained and continued during the pandemic. Objective. The aim of this
study was to assess the impact of COVID-19, preparedness and performance
of national pharmacovigilance systems in participating countries during
COVID-19 pandemic. Methods. This was a cross- sectional study that was
conducted between July and October 2020. National pharmacovigilance
centres in 18 Arab countries in the Middle East were invited to
participate in this study. Descriptive analysis was used to summarize
and present the results of this study. Results. Responses were obtained
from 14 (77.8%) Arab countries. Ten of participating countries (71.4%)
have either specific national PV guidelines or local PV practices during
the COVID-19 pandemic. Adverse events reporting was the main PV activity
that was covered by PV guidelines and practices. National guidelines and
practices covered other PV activities in 8 (57.14%) of the
participating countries. Performance and practices of national PV
centres vary considerably among participating countries during the
pandemic. Conclusion. The findings highlight the differences in
preparedness and performance of different national PV centres in
participating Middle Eastern countries. Improving digital infrastructure
among participating countries could serve as a useful tool to minimize
the impact of the pandemic on PV activities.
The gut microbiome and gut-liver axis in NAFLD
Authors: Guo Chuanyong , Ji Jie , Wu Jianye , Wu Liwei , Feng Jiao , Li Jingjing , Yu Qiang , Dai Weiqi , Li Yan , Zheng Yuanyuan
Published: January 2024

Globally, nonalcoholic fatty liver disease (NAFLD) is the most common
liver disease with an incidence rate ranging from 6%–35% in adult
populations. NAFLD pathogenesis is closely related to insulin resistance
(IR) and the genetic susceptibility of acquired metabolic stress liver
injury. Similarly, the gut microbiota in NAFLD is being revaluated by
scientists as the gut and liver influence each other via the gut-liver
axis. This review focuses on the main mechanisms behind the intestinal
microbiota promotion of NAFLD occurrence and development, and outlines
new strategies to target the intestinal microbiota to facilitate NAFLD
therapies. The enterohepatic circulation of bile acids (BAs), deficient
intestinal barriers and increased permeability, and excessive gut
microbial metabolites all contribute to NAFLD deterioration. Equally,
lifestyle and diet therapy, antibiotics, probiotics and prebiotics, and
fecal microbiota transplantation (FMT) may provide reliable and safe
treatment perspectives for NAFLD.
Correction of a theorem in “Wiener index of a fuzzy graph and application to illegal immigration networks”
Authors: ghods masoud , rostami zahra
Published: January 2024

In the article, we review and critique the Corollary and Theorem of
“Wiener index of a fuzzy graph and application to illegal immigration
networks”, and in addition to providing examples of violations, we
modified the Theorem and presented the correct proof using the method of
its authors. Keywords: Fuzzy graph; Connectivity index; Wiener index;
Fuzzy tree; Fuzzy cycle
General health of patients presenting for osteopathy care: a consecutive sampling design using the PROMIS© Global Health measure.
Authors: Vaughan Brett , Mulcahy Jane , Park Alana , Paton Jay , Hender Timothy , Fitzgerald Kylie
Published: January 2024

Rationale, aims and objectives Health-related quality of life (HRQoL) is
comprised of the physical, social and mental health domains. A wide
variety of single and multi-item measures of HRQoL are available. The
PROMIS© V1.2 Scale – Global Health is a 10-item measure covering the
physical, social and mental health domains. The aim of the study was to
explore the use of the PROMIS© V1.2 Scale – Global Health in a patient
cohort seeking care for a musculoskeletal care. Method Patients an
osteopathy clinic (Melbourne, Australia) were invited to complete the
PROMIS© V1.2 Scale – Global Health along with other health demographics
prior to their initial consultation. The PROMIS© V1.2 Scale – Global
Health was scored as per the instructions. Inferential and correlation
statistics were used to explore associations with patient age, gender
and complaint chronicity. Results Three hundred and ninety-five (n=395)
completed the PROMIS© V1.2 Scale – Global Health scale. The Physical
Health mean T-score was 46.04 (+/- 6.06) and the Mental Health mean
T-score was 49.38 (+/- 7.26). Age and complaint chronicity were not
significantly different for both the Physical and Mental health
T-scores. Physical health mean T-scores were lower for female patients
compared to males with a medium effect size (p<0.01, d=0.31).
Conclusion(s) Physical health scores were lower than the American
general population norm. However, this is to be expected to given the
patient cohort sought care for a musculoskeletal complaint. The PROMIS©
V1.2 Scale – Global Health has the potential to be utilised as a
patient-reported outcome measure for those patients seeking
musculoskeletal care.
Being a medical student in the shadow of the COVID-19 Pandemic: Psychological reactions of Turkish medical students, and their views on distance education and working on the front line
Authors: Tanrıverdi Esra Çınar , Sincan Suat , Ozkurt Zulal , Sahingoz Mine , Kasali Kamber , Layik Mehmet Emin
Published: January 2024

Background: The COVID-19 pandemic had significant effects on medical
students. Objectives: This study aimed to investigate the psychological
impact of the COVID-19 pandemic on preclinical medical students and
determine their views about distance education and working on the
frontline. Methods: A cross-sectional study was conducted on 722
preclinical medical students. Data were collected with an online
questionnaire between 20 and 27 December 2020. A data collection form
including questions about sociodemographic characteristics, opinions
about distance education and frontline working, the Impact of Event
Scale-Revised (IES-R), and the Insomnia Severity Index (ISI) scales was
used for data retrieval. Results: The students’ mean age was 20.7±1.6
years, and 393 (54.4%) were female. Of the students, 699 (96.8%) were
concerned about their education, 181 (25.1%) had post-traumatic stress
disorder, and 171 (23.6%) had insomnia. Post-traumatic stress was
higher in women compared to men (χ2 =3.916, p=0.048), in those who had
acquaintances with COVID-19 compared to those who had not (χ2 =12.798,
p<0.001), those who had a fear of COVID-19 contamination to
their relatives compared to those who did not have such a fear (χ2
=34.463, p<0.001), those who followed COVID-19-related news on
social media compared to those who did not follow such information (χ2
=8.250, p=0.004), and those who had a high level of anxiety about the
interruption of their education compared to those who had less anxiety
(χ2 =42.147, p<0.001). PTSD was significantly higher in those
who had negative opinions towards distance education (χ2 =17.340,
p<0.007), and those with internet connection and quota
problems (p<0.001 and p=0.007 respectively). Conclusion: While
students are experiencing the psychological effects of the pandemic,
they also worry about the interruption of their education. Educators who
prepare students for the upcoming pandemics should also be aware of the
psychological effects and implement remedial interventions for their
mental health
A SQUAMOSA PROMOTER BINDING PROTEIN, LeSPL-CNR targeted by SlymiR157 negatively regulates Fe deficiency response in tomato roots
Authors: Zhu Hui Hui , Wang Jia-Yi , Jiang Dan , Hong Yiguo , Jiming Xu , Zheng Shao Jian , Yang Jian Li , Chen Wei Wei
Published: January 2024

Iron (Fe) homeostasis is critical for plant growth, development and
stress response, which is tightly controlled by intricated regulatory
networks in which transcription factors (TFs) play a central role.
Whilst a series of basic helix-loop-helix (bHLH) TFs have been
functionally characterized to contribute to Fe homeostasis, regulatory
layers beyond bHLH TFs remain largely unclear. Here, we demonstrate that
a SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) TF, LeSPL-CNR, negatively
regulates Fe deficiency responses in tomato roots. Fe deficiency rapidly
repressed the expression of LeSPL-CNR. However, Fe-deficiency-responses
were intensified in two LeSPL-CNR CRISPR/Cas9 gene editing transgenic
lines compared with wild-type plants. By comparative transcriptome
analyses, we identified 47 Fe-deficiency responsive genes including
SlbHLH101 whose expression were negatively regulated by LeSPL-CNR.
LeSPL-CNR is localized to nucleus and yeast one-hybrid and luciferase
reporter assays revealed that LeSPL-CNR could interact with GTAC motif
and BOX4 motif of SlbHLH101 promoter to repress its expression.
Moreover, Fe deficiency-induced expression inhibition of LeSPL-CNR is
correlated well with SlymiR157 expression induction. Additionally,
transgenic tomato overexpressing SlymiR157 displayed improved Fe
deficiency responses similar to that of LeSPL-CNR loss-of-function
mutants. Altogether, we propose that miR157-LeSPL-CNR module provided an
additional pathway that acts upstream of SlbHLH101 to regulate Fe
homeostasis in tomato roots.
The biofilm characteristics and management of skin flap infection following cochlear implantation: A prospective study from 2001 to 2021
Authors: Chen Xi-Hang , Chen Yuqing , Zhang Rong , Ye Shengnan , Lin Zhongyang , Lin Chang
Published: January 2024

Objective: To assess the clinical features and the management of skin
flap infection (SFI) following cochlear implantation (CI) and to
characterize the biofilm features by the scanning electron
microscopy.Setting: The study was conducted at a tertiary care
center.Participants: A total of 1,251 patients receiving CI in the First
Affiliated Hospital of Fujian Medical University between August 2001 and
March 2021 were enrolled. Scanning electron microscopy was utilized for
characterizing the etiology of infection. Main outcome measures: A
proposed stratification system was applied to optimize treatments for
post-operation flap infection.Results: After CI, SFI was reported in 16
patients (1.28%) and patients under 18-year-old were more prone to flap
infection. Staphylococcus Aureus was found to be the most common
bacterial culprit for flap infection, with 6 cases explored in this
group (6/16, 37.5%). Bacterial biofilm was observed within the
jelly-like substance on the surface of CI equipment of SFI patients. A
two-stage stratification was proposed for optimizing the treatment
schemes. Conservative therapy was recommended for stage I cases while
surgical treatment was the preferred method for stage II
patients.Conclusions: Pediatric patients are more susceptible to SFI
after CI. The formation of bacterial biofilm may be the vital cause of
SFI. The proposed stratification can facilitate the management of SFI.