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BROWSE 24,896 MULTI-DISCIPLINARY RESEARCH PREPRINTS

covid-192567terrestrial642infectious diseases551clinical
pharmacology536general505oncology443epidemiology416vertebrate402ecological
experiment348general obstetrics342ecosystem318virus310



MOST RECENT

Barcoding and traditional health practitioner perspectives are informative to
monitor...

Fortunate Phaka

and 7 more

October 04, 2022
Published literature suggests that indigenous cultural practices, specifically
traditional medicine, are commonplace among urban communities contrary to the
general conception that such practices are associated to rural societies. We
reviewed literature for records of herptiles sold by traditional health
practitioners in urban South Africa, then used visual confirmation surveys, DNA
barcoding, and folk taxonomy to identify the herptile species that were on sale.
Additionally, interviews with 11 SePedi and IsiZulu speaking traditional health
practitioners were used to document details of the collection and pricing of
herptile specimens along with the practitioners’ views of current conservation
measures aimed at traditional medicine markets. The herptile specimens sold by
traditional health practitioners included endangered and non-native species. The
absorbance ratios of DNA extracted from the tissue of herptiles used in
traditional medicine were found to be unreliable predictors of whether those
extractions would be suitable for downstream applications. From an initial set
of 111 tissue samples, 81 sequencing reactions were successful and 55 of the
obtained sequences had species level matches to COI reference sequences on the
NCBI GenBank and/or BOLD databases. Molecular identification revealed that
traditional health practitioners sometimes mislabel the species they use. The
mixed methodology employed here is useful for conservation planning as it
updates knowledge of animal use in indigenous remedies and can accurately
identify species of high conservation priority. Furthermore, the study
highlights the possibility of collaborative conservation planning with
traditional health practitioners.
Alternation in follow-up echocardiographic indices in patients with COVID-19: a
prosp...

Yeganeh Pasebani

and 8 more

October 03, 2022
Background Cardiovascular complications are frequently reported among patients
with pulmonary coronavirus disease 2019 (COVID-19) infection. Echocardiography
has been immensely implemented for diagnosing cardiovascular involvements. We
aimed to evaluate the changes in echocardiographic parameters in health care
workers infected with COVID-19 during follow-up. Methods This prospective study
was conducted during Iran’s third COVID-19 wave in November 2020 among health
care workers who were infected with COVID-19 but otherwise healthy. A total of
100 patients underwent echocardiographic examination six to eight weeks
following recovery, an early follow-up. Six months after the COVID-19 diagnosis,
as the late follow-up, 63 subjects underwent echocardiographic evaluations.
Moreover, based on clinical and radiological evidence, individuals were
categorized into two groups of non-severe and severe COVID-19. Results The
participants’ mean age was 40.4±8.1 years. In the non-severe COVID-19 group,
Right Ventricle Free-Wall Global Longitudinal Strain (RVFWGLS) significantly
decreased in the follow-up echocardiogram (-32.3±4.6% vs. -28.8±5.8%,
p-value=0.002). RV Fraction Area Change (RV-FAC) (46.6% [43.6-53] vs. 39.7%
[25-43] , p-value <0.001) and, Tricuspid Annular Plane Systolic Excursion
(TAPSE) (21 mm [19-24] vs. 23 mm [20-25], p-value=0.09) did not show a
significant change. In the severe COVID-19 group in late echocardiogram, RVFWGLS
showed no statistically significant change (-28.3%±3.5 vs. -28.6%±5.1,
p-value=0.79). The RV-FAC (47.2% [42.3-52.2] vs. 36.4% [31.1-45], p-value=0.002)
showed a significant decrease, and TAPSE (22.5 mm [19.1-24.2] vs. 23 mm [21-25],
p-value= 0.55) was comparable. Conclusion Although LV and RV functions did not
vary significantly over time in our entire cohort, different patterns of changes
were discovered according to baseline function.
Chronic high glucose causes podocyte epithelial-mesenchymal transition through
lactat...

Ting Zheng

and 6 more

October 03, 2022
Background and Purpose: Diabetic nephropathy (DN) closely relates to
morphological and functional changes in podocytes, and anaerobic glycolysis
represents the predominant energy source of podocytes. However, it is unknown
whether lactate accumulation in chronic high glucose caused
epithelial-mesenchymal transition (EMT) of podocytes through lactate-derived
histone lactylation. Experimental Approach: We examined biomarkers of podocytes
and mesenchymal cells as well as lactylation of histone lysine residues (HKla)
in mouse MPC cells cultured with high glucose (HG) or lactate (LA). Moreover,
these indices were observed in MPCs after HG co-culture with multiple
interventions of lactate levels, and differently expressed genes (DEGs) were
screened using RNA sequencing. Finally, renal pathological characteristics and
histone lactylation were investigated in diabetic mice with lactate-lowering
treatments. Key Results: Both HG and LA decreased nephrin levels while increased
collagen IV levels in MPCs, and HG and LA stimulation synchronously elevated
HKla levels. However, co-treatment with oxamate or dichloroacetate reducing
lactate levels alleviated decreases in nephrin and ZO-1 levels and increases in
collagen IV and α smooth muscle actin levels as well as HKla levels in
HG-cultured MPCs, but co-treatment with rotenone diversely affected these
indices. RNA sequencing found eleven DEGs in HG-cultured MPCs after oxamate or
dichloroacetate intervention and qPCR experiments validated four of them.
Importantly, oxamate or dichloroacetate treatment attenuated renal functions,
EMT, and histone lactylation in kidney of diabetic mice. Conclusion and
Implications: This study clarified that lactate mediated chronic high
glucose-caused podocyte EMT through lactate-induced histone lactylation, and
then promoted the pathological process of DN.
Fully Integrated downstream process to enable Next Generation Manufacturing

Irina Ramos

and 6 more

October 03, 2022
Next generation manufacturing (NGM) has evolved over the past decade to a point
where large biopharmaceutical organizations are making large investments in the
technology and considering implementation in clinical and commercial processes.
There are many well-considered reasons to implement NGM. For the most part,
organizations will not fund NGM unless the implementation benefits the funding
organization by providing reduced costs, reduced time or additional needed
capabilities. Productivity improvements gained from continuous purification are
shown in this work, which used a new system that fully integrates and automates
several downstream unit operations of a biopharmaceutical process to provide
flexibility and easy implementation of NGM. The equipment and automation
supporting NGM can be complicated and expensive. Biopharmaceutical Process
Development considered two options: (1) design its own NGM system or (2) buy a
pre-built system. PAK BioSolutions (Virginia, US), provides a turn-key automated
and integrated system that can operate up to four continuous purification stages
simultaneously, while maintaining a small footprint in the manufacturing plant.
The PAK system provides significant cost benefits (~10x lower) compared to the
alternative – integration of many different pieces of equipment through a
Distributed Control System (DCS) that would require significant engineering time
for design, automation and integration. Integrated and Continuous
Biomanufacturing can lead to significant reductions in facility size, reduced
manufacturing costs, and enhanced product quality when compared to the
traditional batch mode of operation. The PAK system uses new
automation strategies that robustly link unit operations. We present the
optimized process fit, sterility and bioburden control strategy, and automation
features (such as pH feedback control and in-line detergent addition) that
enabled continuous operation of a 14 day end-to-end monoclonal antibody
purification process at the clinical manufacturing scale.
Discovering Interactions in Augmentation Strategies: Impact of Duloxetine on the
Meta...

Teresa Margraff

and 5 more

October 03, 2022
Objective: Although clinically widespread, scientific evidence for augmentation
strategies in the treatment of severe mental illnesses is still limited.
Combining different drugs increases the potential for drug-drug interactions
enhancing the risk of adverse drug reactions. We aimed to unravel potential
pharmacokinetic interactions between ari-piprazole and duloxetine. Methods:
Plasma concentrations of aripiprazole from a large therapeutic drug monitoring
da-tabase were analyzed. Two groups of 78 patients each, receiving aripiprazole
as a monotherapy, or combined with duloxetine, were compared addressing a
potential impact of duloxetine on the metabolism of aripiprazole being reflected
in higher plasma concentrations of aripiprazole and higher dose-adjusted plasma
concentra-tions (C/D). Results: Patients co-medicated with duloxetine showed
significantly higher plasma concen-trations of aripiprazole (p=0.02) than in the
control group by 54.2% while the dose-adjusted plasma concentrations were 45.6%
higher in the co-medication group (p=0.001). Conclusions: Combining duloxetine
and aripiprazole leads to significantly higher drug concentra-tions of
aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a
lesser extent of CYP3A4 by duloxetine. Clinicians have to consider potentially
occurring adverse drug reactions caused by increased plasma levels of
aripiprazole when adding duloxetine to a treatment regimen with aripiprazole.
Inclusion Body Myositis Triggerred with Long-term Imatinib Use

Rabia Deniz

and 6 more

October 03, 2022
Inclusion body myositis (IBM) is an acquired myopathy of both inflammatory and
degenerative nature. Here we report a case of IBM associated with prolonged use
of imatinib not reported in the literature so far. An 81 years old male with a
history of gastrointestinal stromal tumor (GIST) operated 8 years ago was
evaluated for the progressive loss of weight and muscle strength leading to
total immobilization in 6 months. He was under imatinib for 8 years despite the
remission of GIST. Physical examination disclosed diffuse loss of muscle
strength, most prominently involvement of distal upper and proximal lower
extremity in an asymmetrical pattern with normal serum creatinine kinase level
(CK). Further investigations including bilateral thigh MRI, electromyography
(EMG), and PET/CT suggested myositis and degenerative myopathy and ruled out any
malignancy. Quadriceps femoris biopsy proved the diagnosis of IBM and no trigger
except for imatinib was displayed. Clinical improvement in terms of wieght loss
and muscle weakness was achieved after discontinuation of imatinib. Since
imatinib is widely used in different conditions, it is important to be aware of
even its rare adverse effects. Poor response of IBM to conventional
immunosuppressive agents enhances the value of etiology identification to
relieve symptoms in addition to supportive care.
Methylprednisolone use in children with severe pneumonia caused by SARS-CoV-2

Osman Oguz Demir

and 7 more

October 03, 2022
Objective: This study aimed to evaluate the effectiveness and optimal use of
corticosteroids in children with severe coronavirus disease 2019 (COVID-19)
pneumonia. Methods: We conducted a retrospective study and included patients
(aged<18 years) with severe COVID-19 pneumonia and/or acute respiratory distress
syndrome (ARDS) who received standard doses (2–4 mg/kg/day) and high doses (>250
mg/day) of methylprednisolone (MPZ). We adjusted for patients on steroid
treatments with a propensity score and patient survival. Results: Fifty-nine
patients were included: 61% were male, the median age was 8 (interquartile range
[IQR], 2–15) years. The overall survival was 84.4% in patients treated with
standard-dose MPZ (n = 45, 76.3%) and 92.2% in patients treated with high-dose
MPZ (n = 14, 23.7%; p = 0.67). The demographic, clinical, and laboratory data
didn’t differ significantly after propensity score matching, apart from
bradycardia, which was a prominent feature of the high-dose group. The clinical
and radiological response rates on Day 7 were higher and the need for invasive
mechanical ventilation (IMV) was lower in the high-dose group. Conclusion: Pulse
MPZ treatment seems to result in better clinical and radiological responses,
with less need for IMV, although the mortality rate doesn’t differ between
standard and high-dose regimens of MPZ.
Cofactor engineering for efficient production of α-farnesene by rational
modification...

sheng-ling Chen

and 3 more

October 03, 2022
α-Farnesene, an acyclic volatile sesquiterpene, plays important roles in
aircraft fuel, food flavoring, agriculture, pharmaceutical and chemical
industries. Here, we enhanced α-farnesene production through reconstructing the
biosynthetic pathways of NADPH and ATP in Pichia pastoris. First, the native
oxiPPP was reconstructed by over-expressing the key enzymes in oxiPPP or/and
inactivating glucose-6-phosphate isomerase (PGI), indicating that combined
over-expression of ZWF1 and SOL3 improves NADPH supply and thus increasing
α-farnesene production while inactivation of PGI was not because of the
decreased cell growth. Next, different expression level of heterologous cPOS5
were introduced into P. pastoris, and found that low intensity expression of
cPOS5 facilitated α-farnesene biosynthesis. Finally, ATP was increased by
overexpression of APRT and inactivation of GPD1. The resultant strain P.
pastoris X33-38 produced 3.09±0.37 g/L of α-farnesene in shake-flask
fermentation, which was 41.7% higher than that of the parent strain. These
results provide a new perspective to construct industrial-strength α-farnesene
producer by rational modification of NADPH and ATP regeneration pathway in P.
pastoris.
A rare case of cortisol and estradiol secreting PNET of the adrenal gland: a
case rep...

Mohammad Naghizadeh

and 4 more

October 03, 2022
: We report a rare case of cortisol secreting extracranial primary
neuroectodermal tumor (PNET) originating from adrenal gland in adulthood. PNETs
are typically not functional, making this case extremely rare. cortisol
secreting PNETS are as of yet, unheard of.
Strategies to prevent self-ligation of adapters used in enzyme mediated
methylation s...

peng Qi

and 14 more

October 03, 2022
In our recent effort of developing methylation-dependent endonuclease mediated
methylation sequencing technology, efficiency and reproducibility were
restrained by adapters' self-ligation. In the present study, three strategies to
prevent self-ligation of adapters used in enzyme mediated methylation sequencing
have been developed. Our data have demonstrated that these strategies can either
inhibit or eliminate the adapters' self-ligation. These strategies are crucial
in enzyme-mediated methylation sequencing and may be useful in some other
genomic sequencing technologies.
Covariance matrix estimation via bilinear shrinkage regularization

Bin Zhang

and 1 more

October 03, 2022
The problem of estimating a covariance matrix plays crucial in signal processing
and other related fields. This paper proposes a novel bilinear shrinkage
estimation by simultaneously regularizing the sample mean and the SCM via the
linear shrinkage technique. Through a one-one mapping of the weight parameters,
the bilinear shrinkage estimation can be expressed as a generalization version
of the well-known linear shrinkage estimation. Available covariance matrix
estimators are developed by parametric and nonparametric methods for different
target matrices. In our numerical simulations, the bilinear shrinkage estimators
can reach lower Frobenius losses compared with the existing linear shrinkage
estimators. Moreover, the proposed covariance matrix estimators can work well in
application to large array signal processing.
Severe rhabdomyolysis associated with etoposide-nedaplatin chemotherapy in a
patient...

Xiaohu Xu

and 3 more

October 03, 2022
Etoposide combined with platinum drugs is the first-line chemotherapy for small
cell lung cancer（SCLC）. Here, we describe the first case with small cell lung
cancer, who developed severe rhabdomyolysis after etoposide-nedaplatin
chemotherapy. He complained of progressive generalized muscle pain and weakness
after first cycle chemotherapy for SCLC, accompanied by elevated creatine kinase
(CK), myoglobin (Mb), alanine aminotransferase (ALT), spartate aminotransferase
(AST) and lactate dehydrogenase (LDH). Examination and inquiry of medical
history were used to exclude the factors of rhabdomyolysis caused by trauma,
strenuous activities, infections, hyperthermia and immunity, the patient was
diagnosed with severe rhabdomyolysis induced by chemotherapy. After treatment
with intravenous fluids and methylprednisolone, the patient’s symptoms were
relieved and laboratory tests were significantly improved. An unexpected
situation is that the lung CT scan showed that the lung mass was significantly
smaller than that before chemotherapy, but the reason is not clear.
Rhabdomyolysis induced by anti-cancer drugs, especially chemotherapy drugs, is
rarely reported and easily overlooked. Therefore, physicians should be aware of
this rare but potentially serious complication when using chemotherapy drugs.

Browse more recent preprints


RECENTLY PUBLISHED IN SCHOLARLY JOURNALS

Geobacter sulfurreducens metabolism at different donor/acceptor ratios

Hanna Marianne Frühauf-Wyllie

and 1 more

September 13, 2022
Geobacter species have great application potential in remediation processes and
electrobiotechnology. In all applications, understanding the metabolism will
enable target-oriented optimization of the processes. The typical electron donor
and carbon source of the Geobacter species is acetate, while fumarate is the
usual electron acceptor. Here, we could show that depending on the
donor/acceptor ratio in batch cultivation of G. sulfurreducens different product
patterns occur. With a donor/acceptor ratio of 1:2.5 malate accumulated as an
intermediate product but was metabolized to succinate subsequently. At the end
of the cultivation, the ratio of fumarate consumed and succinate produced was
approximately 1:1. When fumarate was added in excess, malate accumulated in the
fermentation broth without further metabolization. After the addition of acetate
to stationary cells, malate concentration decreased immediately and additional
succinate was synthesized. Finally, it was shown that also resting cells of G.
sulfurreducens could efficiently convert fumarate to malate without an
additional electron donor. Overall, it was demonstrated that by altering the
donor/acceptor ratio, targeted optimization of the metabolite conversion by G.
sulfurreducens can be realized.
Functional Consequence and Therapeutic Targeting of Cryptic ALK Fusions (ALK fus
) in...

Makia K. Manselle

and 6 more

September 05, 2022
Acute Myeloid Leukemia (AML) patients have a wide array of cytogenetic and
molecular aberrations which can influence response to therapy. Monosomy7 (Mono7)
is a rare subset within pediatric AML (prevalence of 4-5%), that is highly
associated with poor outcomes. Fusions involving the ALK gene (14.3%) were
exclusively identified within this high-risk cohort while absent across all
other AML. Given the dismal outcomes of Mono7, we evaluated the use of
crizotinib, an FDA-approved tyrosine kinase inhibitor, used to treat patients
with ALK fusions. Our findings suggest that crizotinib may serve as a novel
therapy for these patients.
On the left or on the right…side of the table. Where do you stand?

Arnaldo Dimagli

and 1 more

August 26, 2022
Being able to perform surgery first-hand represents the backbone of every
training program and the key to successful development of the new generation of
skilful surgeons. In this issue of the Journal, Comanici et al. presented a
thorough systematic summary of the current evidence on the outcomes of
cardiothoracic operations performed by trainees.1 Taking for granted the
importance of training young surgeons, it is paramount to identify and tackle
any potential obstacles hindering the surgical growth of a trainee.
Acute Lymphoblastic Leukemia of the Central Nervous System Presenting with Rapid
Weig...

Connor P. Hall

and 1 more

August 24, 2022
Acute Lymphoblastic Leukemia of the Central Nervous System Presenting with Rapid
Weight GainConnor P. Hall1 and Alan D. Friedman11Division of Pediatric Oncology,
Johns Hopkins University School of Medicine, Baltimore, Maryland,
USACorrespondence: Alan D. Friedman, MDJohns Hopkins UniversityCRB I, Rm. 253
1650 Orleans St. Baltimore, Maryland 21231 Phone: 410-955-2095; Fax:
410-955-8897 Email: afriedm2@jhmi.eduWord Count: 863Number of Figures: 1Running
Title: Rapid Weight Gain in ALLKey Words: acute lymphoblastic leukemia/ relapse/
weight gain/ central nervous systemAbbreviations:
Total arch replacement versus proximal aortic replacement in acute type A aortic
diss...

Matti Jubouri

and 4 more

August 23, 2022
Background: Acute type A aortic dissection (ATAAD) is a life-threatening medical
condition requiring urgent surgical attention. It is estimated that 50% of ATAAD
die within 24 hours of onset, with the mortality rate is increasing by 1-2%
every additional hour without prompt intervention. A variety of ATAAD surgical
repair techniques exist which has sparked controversy within the literature,
with the main two strategies being proximal aortic replacement (PAR) and total
arch replacement (TAR). Nevertheless, the question of which of these two
strategies if the more optimal is still debatable. Aims: This commentary aims to
discuss the recent study by Sa and colleagues which presents a pooled analysis
of Kaplan-Meier-derived individual patient data from studies with follow-up
comparing aggressive (TAR) and conservative (PAR) approaches to manage ATAAD
patients. Methods: A comprehensive literature search was performed using
multiple electronic databases including PubMed, Ovid, Google Scholar, EMBASE and
Scopus in order to collate the relevant research evidence. Results: The more
aggressive TAR approach for treating ATAAD seems to yield more favourable
results including more optimal long-term survival as well as a lower need for
reoperation. The frozen elephant trunk (FET) technique can be considered the
mainstay TAR technique. Conclusion: It is valid to conclude that TAR with FET is
the superior strategy for managing ATAAD patients.
Adverse complications of Frozen elephant trunk, do we have enough quality data?

Callum Howard

and 3 more

August 23, 2022
Frozen elephant trunk (FET) has in recent times become a mainstay for total arch
replacement (TAR) in aortovascular surgery and is indicated in order to treat a
spectrum of complex aortic pathologies. However, despite associated excellent
post-operative results it is incredibly important to recognise potential adverse
complications such as negative aortic remodelling, endoleak and distal
stent-graft induced new entry so that outcomes can be further improved. Below we
provide commentary on a recent article in the Journal of Cardiac Surgery
discussing the topic. Despite the fascinating outcomes of this systematic review
and meta-analysis the heterogeneity of the literature regarding these adverse
outcomes remains an issue which can only be solved with large multi-centre
trials directly comparing graft types as well as indications for surgery.
Outcomes Following Implementation of a Pediatric Cardio-Oncology Program

Zac Daniels

and 6 more

August 19, 2022
The comprehensive care that cancer patients require has become increasingly
complex and led to the creation of cardio-oncology clinics (COC). Ninety-five
patients were referred to our quaternary care COC. Initiation of oral heart
failure therapy (OHFT) or advanced cardiac therapies within 1 year following
referral were identified and risk factors for these were evaluated. Patients
older at the time of cancer diagnosis and with lower LV ejection fraction were
more likely to require OHFT. COC’s elicit a high degree of clinically actionable
information for pediatric patients suffering from not only cancer, but also
cardiomyopathy, a particularly high-risk patient population.
Commentary to: ‘Comparing Mid-Term Outcomes of Cox-Maze Procedure and Pulmonary
Vein...

Marco Moscarelli

and 1 more

August 17, 2022
There are no solid evidence from literature that compare Cox-Maze with pulmonary
vein isolation technique for atrial fibrillation in the context of concomitant
mitral valve surgery. While the first is perhaps more effective and linked to
higher freedom form atrial fibrillation, it is more invasive compared to the
pulmonary isolation.
The catastrophe of hypoxia in complex aortic surgery

Abraham Kayal

and 2 more

August 16, 2022
The catastrophe of hypoxia in complex aortic surgery
A capable numerical meshless scheme for solving distributed order
time-fractional rea...

Esmail Hesameddini

and 2 more

August 16, 2022
Distributed order fractional differential equations are efficient in describing
physical phenomena because of the differential order distribution. In this
paper, the distributed order time-fractional reaction-diffusion equation is
considered in the sense of Caputo fractional derivative. A hybrid method is
developed based on the Moving Kriging (MK) interpolation and finite difference
method for solving this distributed order equation. First, the distributed
integral is discretized by the $M$-point Gauss Legendre quadrature rule. Then,
the $L2-1_{\sigma}$ method is applied to approximate the solution of the
fractional derivative discretization. Also, the unconditionally stability and
rate of convergence $O(\tau^{2})$ of the time-discrete technique are
illustrated. Furthermore, the MK interpolation is applied in the space variables
discretization. Finally, some examples are presented to indicate the efficiency
of this method and endorsement the theoretical results.
The correlation between COVID-19 vaccination and cardiac surgery: when is safe
to vac...

Sara Zaidi

and 3 more

August 11, 2022
A document by Sara Zaidi, written on Authorea.
Mitigating Esophageal Injury after Atrial Fibrillation Ablation Guided by
Ablation In...

Jason Chinitz

and 1 more

August 09, 2022
Mitigating Esophageal Injury after Atrial Fibrillation Ablation Guided by
Ablation Index; CLOSEr to goalJason S. Chinitz, MD1 and Eli Q. Harris,
MD21.South Shore University HospitalNorthwell HealthBay Shore, NY2. Nassau
University Medical CenterEast Meadow, NYFinancial support : none.Disclosures :
Dr. Chinitz serves on the scientific advisory board for Biosense Webster and has
received consulting fees

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