bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory acceptability of biofortified foods and food products: a systematic review
Authors: Huey Samantha L , Bhargava Arini , Friesen Valerie M , Konieczynski Elsa M , Krisher Jesse T , Mbuya Mduduzi N N , Mehta Neel H , Monterrosa Eva , Nyangaresi Annette M , Mehta Saurabh
Published: August 2023

Context

It is important to understand the sensory acceptability of biofortified food products among target population groups if biofortification is to be realized as a sustainable strategy for mitigation of micronutrient deficiencies, able to be scaled up and applied through programs.

Objective

This systemic review aims to summarize and synthesize the sensory acceptability of conventionally bred iron-, zinc-, and provitamin A–biofortified food products.

Data Sources

MEDLINE (PubMed), AGRICOLA, AgEcon, CABI Abstracts (Web of Science), and organizational websites (eg, those of HarvestPlus and CGIAR and their partners) were searched for relevant articles. No access to any market research that may have been internally conducted for the commercial biofortified food products was available.

Data Extraction

This review identified articles measuring the sensory acceptability of conventionally bred biofortified food products. Extraction of the hedonic ratings of food products was performed.

Data Analysis

An “Acceptability Index %” was defined based on hedonic scoring to determine an overall rating, and used to categorize biofortified food products as “acceptable” (≥70%) or “not acceptable” (<70%). Additionally, this review narratively synthesized studies using methods other than hedonic scoring for assessing sensory acceptability.

Conclusions

Forty-nine studies assessed the acceptability of 10 biofortified crops among children and adults, in mostly rural, low-income settings across Africa, Latin America, and India; food products made from mineral and provitamin A–biofortified food products were generally acceptable. Compared with studies on provitamin–A biofortified food products, few studies (1 to 2 each) on mineral-enhanced crops such as rice, cowpeas, lentils, and wheat were found, limiting the generalizability of the findings. Similarly, few studies examined stored biofortified food products. Few commercial food products have so far been developed, although new varieties of crops are being continuously tested and released globally. Certain crop varieties were found to be acceptable while others were not, suggesting that particular varieties should be prioritized for scale-up. Determining sensory acceptability of biofortified food products is important for informing programmatic scale-up and implementation across diverse populations and settings.
The regulatory effect of intermittent fasting on inflammasome activation in health and disease
Authors: Wang Chenchen , Liu Zhiqin , Cai Jinpeng , Xu Xi
Published: August 2023

Intermittent fasting (IF), one of the most popular diets, can regulate inflammation and promote health; however, the detailed molecular mechanisms are not fully understood. The present review aims to provide an overview of recent preclinical and clinical studies that have examined the effect of IF on inflammasome signaling, and to discuss the translational gap between preclinical and clinical studies. Three databases (PubMed, Web of Science, and Embase) were searched to identify all relevant preclinical and clinical studies up to October 30, 2022. A total of 1544 studies were identified through the database searches, and 29 preclinical and 10 clinical studies were included. Twenty-three of the 29 preclinical studies reported that IF treatment could reduce inflammasome activation in neurological diseases, metabolic and cardiovascular diseases, immune and inflammatory diseases, gastrointestinal diseases, and pulmonary diseases, and 7 of the 10 clinical studies demonstrated reduced inflammasome activation after IF intervention in both healthy and obese participants. Among various IF regimens, time-restricted eating seemed to be the most effective one in terms of inflammasome regulation, and the efficacy of IF might increase over time. This review highlights the regulatory effect of IF on inflammasome activation in health and disease. Future studies using different IF regimens, in various populations, are needed in order to evaluate its potential to be used alone or as an adjunct therapy in humans to improve health and counteract diseases.
Management of Medullary Thyroid Cancer: Patterns of Recurrence and Outcomes of Reoperative Surgery
Authors: Papachristos Alexander J , Nicholls Laura E , Mechera Robert , Aniss Ahmad M , Robinson Bruce , Clifton-Bligh Roderick , Gill Anthony J , Learoyd Diana , Sidhu Stan B , Glover Anthony , Delbridge Leigh , Sywak Mark
Published: August 2023

Background

There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center.

Patients and Methods

A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data.

Results

In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018).

Conclusion

Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control.
New conjecture on exact Dirac zero-modes of lattice fermions
Authors: Yumoto Jun , Misumi Tatsuhiro
Published: August 2023

We propose a new conjecture on the relation between the exact Dirac zero-modes of free and massless lattice fermions and the topology of the manifold on which the fermion action is defined. Our conjecture claims that the maximal number of exact Dirac zero-modes of fermions on finite-volume and finite-spacing lattices defined by a discretizing torus, hyperball, their direct-product space, and hypersphere is equal to the summation of the Betti numbers of their manifolds if several specific conditions on lattice formulations are satisfied. We start with reconsidering exact Dirac zero-modes of naive fermions on the lattices whose topologies are a torus, hyperball, and their direct-product space (TD × Bd). We find that the maximal number of exact zero-modes of free Dirac fermions is in exact agreement with the sum of Betti numbers $\sum ^{D}_{r=0} \beta _{r}$ for these manifolds. Indeed, the 4D lattice fermion on a torus has up to 16 zero-modes while the sum of Betti numbers of T4 is 16. This coincidence holds also for the D-dimensional hyperball and their direct-product space TD × Bd. We study several examples of lattice fermions defined on a certain discretized hypersphere (SD), and find that it has up to two exact zero-modes, which is the same number as the sum of Betti numbers of SD. From these facts, we conjecture the equivalence of the maximal number of exact Dirac zero-modes and the summation of Betti numbers under specific conditions. We discuss a program for proof of the conjecture in terms of Hodge theory and spectral graph theory.
Patients with rheumatoid arthritis presenting with mono- or oligo-arthritis and high VAS-ratings remain the most fatigued during 5 years of follow-up
Authors: Boeren Anna M P , Verstappen Marloes , Looijen Agnes E M , de Jong Pascal H P , van der Helm-van Mil Annette H M
Published: August 2023

Objectives

The severity of fatigue in RA has improved very little in recent decades, leaving a large unmet need. Fortunately, not all RA patients suffer from persistent fatigue, but the subgroup of patients who suffer the most is insufficiently recognizable at diagnosis. As disease activity is partly coupled to fatigue, DAS components may associate with the course of fatigue. We aimed to identify those RA patients who remain fatigued by studying DAS components at diagnosis in relation to the course of fatigue over a 5-year follow-up period in two independent early RA cohorts.

Methods

In all, 1560 consecutive RA patients included in the Leiden Early Arthritis Cohort and 415 RA patients included in the tREACH trial were studied. Swollen joint count, tender joint count, ESR and Patient Global Assessment (PGA) [on a Visual Analogue Scale (VAS)] were studied in relation to fatigue (VAS, 0–100 mm) over a period of 5 years, using linear mixed models.

Results

Higher tender joint count and higher PGA at diagnosis were associated with a more severe course of fatigue. Furthermore, patients with mono- or oligo-arthritis at diagnosis remained more fatigued. The swollen joint count, in contrast, showed an inverse association. An investigation of combinations of the aforementioned characteristics revealed that patients presenting with mono- or oligo-arthritis and PGA ≥ 50 remained the most fatigued over time (+20 mm vs polyarthritis with PGA < 50), while the DAS course over time did not differ. This subgroup comprised 14% of the early RA population. Data from the tREACH trial showed similar findings.

Conclusion

The RA patients who remain the most fatigued were those characterized by mono- or oligo-arthritis and high PGA (VAS ≥ 50) at diagnosis. This understanding may enable early-intervention with non-pharmacological approaches in dedicated patient groups.
Older Working Persons and the Gender Pay Gap: Estimations Using Gender Norm Variables in Peru
Authors: Cruz Saco María Amparo , Gil Mirian , Vergaray Valeria
Published: August 2023

This study investigated the gender pay gap in Peru among older working persons, i.e. sixty years of age and older, who represent more than half of this population. Cultural and social gender norm variables were incorporated as regressors in a Mincer-type income model. Household surveys for the period 2004–2021 were used to estimate the total gap and regional heterogeneities. Three gender norm variables substantially increase the explained portion of the gender pay gap in the Oaxaca–Blinder decomposition. We find that the estimated pay gap among older working persons is 68 percent, larger than the gender pay gap for younger workers as documented in diverse contributions.
CGMP Compliant Microfluidic Transfection of Induced Pluripotent Stem Cells for CRISPR-Mediated Genome Editing
Authors: Bohrer Laura R , Stone Nicholas E , Wright Allison T , Han Sewoon , Sicher Ian , Sulchek Todd A , Mullins Robert F , Tucker Budd A
Published: August 2023

Inherited retinal degeneration is a term used to describe heritable disorders that result from the death of light sensing photoreceptor cells. Although we and others believe that it will be possible to use gene therapy to halt disease progression early in its course, photoreceptor cell replacement will likely be required for patients who have already lost their sight. While advances in autologous photoreceptor cell manufacturing have been encouraging, development of technologies capable of efficiently delivering genome editing reagents to stem cells using current good manufacturing practices (cGMP) are needed. Gene editing reagents were delivered to induced pluripotent stem cells (iPSCs) using a Zephyr microfluidic transfection platform (CellFE). CRISPR-mediated cutting was quantified using an endonuclease assay. CRISPR correction was confirmed via digital PCR and Sanger sequencing. The resulting corrected cells were also karyotyped and differentiated into retinal organoids. We describe use of a novel microfluidic transfection platform to correct, via CRISPR-mediated homology-dependent repair (HDR), a disease-causing NR2E3 mutation in patient-derived iPSCs using cGMP compatible reagents and approaches. We show that the resulting cell lines have a corrected genotype, exhibit no off-target cutting, retain pluripotency and a normal karyotype and can be differentiated into retinal tissue suitable for transplantation. The ability to codeliver CRISPR/Cas9 and HDR templates to patient-derived iPSCs without using proprietary transfection reagents will streamline manufacturing protocols, increase the safety of resulting cell therapies, and greatly reduce the regulatory burden of clinical trials.
Dermatofibroma Versus Dermatofibrosarcoma Protuberans: A Nuclear Morphology Study
Authors: Khamdan Fatema , Brailsford Caroline , Dirr McKenzie A. , Sagut Pelin , Nietert Paul J. , Elston Dirk
Published: August 2023

The locally invasive soft-tissue sarcoma, dermatofibrosarcoma protuberans (DFSPs), shares certain histologic features of the much more common and benign dermatofibroma (DF). While immunohistochemical stains, specifically cluster of differentiation 34 and Factor XIIIa, can be used to distinguish the 2 entities using microscopy, these markers are not entirely sensitive nor specific. Three-dimensionally, DFSP nuclei resemble a “puck” or “coin”-like shape. As hematoxylin/eosin-stained slides are prepared, these “puck” nuclei are fixed in an infinite number of orientations depending on their current position in rotation about their axes within the tumor cells. Under histological examination, this random nuclear positioning produces the appearance of 2 predominate morphologies: an ovoid “disk” shape (en face) and a narrow spindled shape (side view), which distribute in a roughly 50:50 ratio throughout the tumor sample slide. Nuclear morphology was analyzed in 324 DFSP and DF samples at high magnification (×400) to determine the presence or absence of a predominant morphology in which nuclei appear to alternate between an ovoid (en face) and spindled (side view) throughout most of the tumor sample. An alternating ovoid-spindled nuclear morphology was the predominant cytology in 98% of DFSP and was not predominant in 100% of DF samples (P < 0.001). This morphology was found to be highly specific (Sp = 1) and sensitive (Sn = 0.98) for DFSP. This unique nuclear morphology may be a more sensitive and specific diagnostic tool in identifying DFSP from DF in comparison with costly immunohistochemical stains.
Anaplastic Large Cell Transformation of Mycosis Fungoides: Case Report and Review of the Literature
Authors: Flerova Elizaveta , Alpdogan Onder , Bhatti Safiyyah , Nikbakht Neda , Wang Zi-Xuan , Gong Jerald Z.
Published: August 2023

We report a 48-year-old man with CD30+ large cell transformation of mycosis fungoides (tMF) with distinctive anaplastic morphology. The patient initially presented with folliculotropic and syringotropic mycosis fungoides (MF) manifested as occipital scalp plaque and trunk and extremities patches. Six years later, he progressed to the tumor stage from his scalp lesion and developed cervical lymphadenopathy. Lymph node and scalp biopsies showed diffuse infiltration of CD30+ anaplastic cells with multinucleated, hallmark-like, Hodgkin–Reed–Sternberg-like, histiocytoid forms, indistinguishable from anaplastic large cell lymphoma (ALCL). T-cell receptor gamma gene (TCRg) rearrangement studies revealed identical clones in the initial MF scalp lesion and nodal anaplastic lesion, confirming the transformation. Ancillary studies showed absence of IRF4/DUSP22 and ALK rearrangements and positive RB1, SMARCA4, SOCS1, and TP53 mutations. The patient achieved partial response with systemic chemotherapy. Our case is an example of tMF presenting as the morphology and phenotype of ALCL. Because clinical behavior and therapeutic options of tMF and primary cutaneous ALCL may be different, it is clinically relevant to differentiate these 2 entities. The proof of clonal relationship may be useful in diagnostically challenging cases with features overlapping between tMF and primary cutaneous ALCL.
Defect rocksalt structures in the La-Na-N system
Authors: Yuan Yao , Kloß Simon D. , Attfield J. Paul
Published: August 2023

Sodium azide (NaN
3
) is a versatile nitrogen source that can be used for the synthesis of new nitrides under high-pressure and temperature conditions. Reactions between lanthanum nitride (LaN) and sodium azide (NaN
3
) at 800°C under 8 GPa pressure have led to the discovery of two defect rocksalt phases which are the first reported ternaries in the La-Na-N system. Preliminary structure assignments have been made based on fits to powder X-ray diffraction profiles. One phase is La

1−
x

Na

3
x

N with vacancies at octahedral La sites and interstitial tetrahedral Na cations. This phase has a tetragonally distorted rocksalt structure (space group
I
4

/

mmm
,
a
 = 3.8704(2) and
c
 = 5.2098(3) Å for nominal
x
 = 0.10) and the distortion decreases with increasing Na content (space group
I
4

/

mmm
,
a 
= 3.8060(2) Å,
c 
= 5.2470(3) Å for nominal
x
 = 0.14), further giving a cubic phase (
a
 = 5.3055(2) Å) for nominal
x
 = 0.25. This coexists with another cubic

F
m

3
¯

m

phase (
a
 = 5.1561 (5) Å), tentatively identified as rocksalt ‘NaN
1/3
’ stabilized by a small amount of La; NaLa

y

N

(1+3
y
)/3

with
y
 ≈ 1%. These initial investigations reveal that the high-pressure La-Na-N phase diagram may be rich in defect rocksalt-type materials although further work using neutron diffraction will be needed to confirm the structures.

This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.
P-V-T
equation of state of boron carbide
Authors: Somayazulu Maddury , Ahart Muhtar , Meng Yue , Ciezak Jennifer , Velisavlevic Nenad , Hemley Russell J.
Published: August 2023

We report the
P-V-T
equation of state measurements of B
4
C to 50 GPa and approximately 2500 K in laser-heated diamond anvil cells. We obtain an ambient temperature, third-order Birch–Murnaghan fit to the
P-V
data that yields a bulk modulus
K
0
of 221(2) GPa and derivative, (d
K
/d
P
)
0
of 3.3(1). These were used in fits with both a Mie–Grüneisen–Debye model and a temperature-dependent, Birch–Murnaghan equation of state that includes thermal pressure estimated by thermal expansion (
α
) and a temperature-dependent bulk modulus (d
K
0
/d
T
). The ambient pressure thermal expansion coefficient (
α
0 
+ α
1
T
), Grüneisen
γ
(
V
) = 
γ
0
(
V
/
V
0
)

q

and volume-dependent Debye temperature, were used as input parameters for these fits and found to be sufficient to describe the data in the whole
P-T
range of this study.

This article is part of the theme issue ‘Exploring the length scales, timescales and chemistry of challenging materials (Part 1)’.
A structural study of PrCrO
3
under extreme conditions: a comparison with the effects of doping
Authors: Bull C. L. , Funnell N. P. , Ridley C. J.
Published: August 2023

The nuclear and magnetic structure of

PrCrO

3

has been investigated using neutron and X-ray powder diffraction as a function of pressure and temperature. The orthorhombic symmetry (space group

P
b
n
m

) remains stable up to the highest temperature (1500 K) and pressure (approx.

6
 

GPa

) considered. There is a crossover in the magnitude of the
a-
and
b
-lattice parameters at approximately 1135 K, caused by competing effects of octahedral tilting and distortion. The material is antiferromagnetic (

T
N

≈
240

 K) with

P

b
′

n
′

m

symmetry, with a maximum moment of

2.34
(
2
)

μ
b

on the

Cr

3
+

sites aligned along the direction of the

a

-axis. The application of pressure shows an abnormal softening in the unit-cell volume, which is suggestive of a continuous approach to a second-order phase transition. Raman spectroscopy measurements at ambient temperature were collected as a function of pressure up to approximately

12

 GPa, with discontinuous mode behaviour further suggesting the existence of a transition above 7 GPa. The measured structural changes in

PrCrO

3

are compared extensively in the wider context of other lanthanide orthochromites, and the comparative effects of
A
- and
B
-site substitution on the polyhedral tilts and distortion are discussed.

This article is part of the theme issue ‘Exploring the length scales, timescales and chemistry of challenging materials (Part 1)’.
Thermodynamic anomalies, polyamorphism and all that
Authors: Fijan Domagoj , Wilson Mark
Published: August 2023

The appearance and evolution of thermodynamics anomalies, and related properties, are studied for two classes of system, modelling those dominated by covalent and ionic interactions, respectively. Such anomalies are most familiar in the density but are also present in other thermodynamics variables such as the compressibility and heat capacity. By systematically varying key model parameters the emergence and evolution of these anomalies can be tracked across the phase space. The interaction of the anomalies can often be rationalized by thermodynamics ‘rules’. The emergence of these anomalies may also be correlated with the appearance of polyamorphism, the existence of multiple amorphous states which differ in density and entropy.

This article is part of the theme issue ‘Exploring the length scales, timescales and chemistry of challenging materials (Part 1)’.
Stable and metastable structures of tin (IV) oxide at high pressure
Authors: Sneed Daniel T. , Smith G. Alexander , Kearney John S. C. , Childs Christian , Park Changyong , Lawler Keith V. , Salamat Ashkan , Smith Dean
Published: August 2023

We have analysed

SnO

2

with a combination of synchrotron X-ray diffraction and X-ray absorption spectroscopy across a pressure range of

0
→
82.9

 GPa with thermal annealing by a

CO

2

laser allowing access to all of the known high-density polymorphs of

SnO

2

, and here report their crystallographic information. The metastability of the post-rutile

α

-

PbO

2

and

PdF

2

structures in

SnO

2

are investigated by experiment and PW-DFT simulations, revealing a complex energetic landscape and suggesting a significant dependence of the observed phases on the pressure–temperature pathway taken in experiment.

This article is part of the theme issue ‘Exploring the length scales, timescales and chemistry of challenging materials (Part 1)’.
The structure of molten calcium ferrite under various redox conditions
Authors: Shi Caijuan , Alderman Oliver L. G. , Tamalonis Anthony , Weber J. K. R. , Benmore Chris J.
Published: August 2023

Laser-heated melts based on the 43CaO–57Fe
2
O

3−
x

eutectic, close to the calcium ferrite (CF) composition, were measured with high-energy X-ray diffraction using aerodynamic levitation over a range of redox states controlled by CO/CO
2
gas atmospheres. The iron–oxygen coordination number was found to rise from 4.4 ± 0.3 at 15% Fe
3+
to 5.3 ± 0.3 at 87% Fe
3+
. Empirical potential structure refinement modelling was used to obtain the ferric and ferrous partial pair distribution functions. It was found that the Fe
2+
iron–oxygen coordination number is consistently approximately 10% higher in CF than in pure iron oxide, while Fe
3+
is essentially identical in all but the most oxygen-rich environments (where it is higher in CF compared with FeO

x

). The model also shows calcium octahedra to be the dominant species across all redox environments, although the population of CaO
7
increases with the availability of oxygen at the expense of CaO
4
and CaO
5
.

This article is part of the theme issue ‘Exploring the length scales, timescales and chemistry of challenging materials (Part 1)’.
Exploring the length scales, timescales and chemistry of challenging materials (Part 1)
Authors: Wilding Martin C. , Sella Andrea , Howard Christopher A. , Jorge Sobrido Ana , Catlow C. Richard A.
Published: August 2023

This themed issue explores the different length scales and timescales that determine the physics and chemistry of a variety of key materials, explored from the perspective of a wide range of disciplines, including physics, chemistry, materials science, Earth science and biochemistry. The topics discussed include catalysis, chemistry under extreme conditions, energy materials, amorphous and liquid structure, hybrid organic materials and biological materials. The issue is in two parts, with the present part exploring glassy and amorphous systems and materials at high pressure.

This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.
Glass transition temperatures and crystallization kinetics of a synthetic, anhydrous, amorphous calcium-magnesium carbonate
Authors: Hess Kai-Uwe , Schawe Jürgen E. K. , Wilding Martin , Purgstaller Bettina , Goetschl Katja E. , Sturm Sebastian , Müller-Caspary Knut , Sturm Elena V. , Schmahl Wolfgang , Griesshaber Erika , Bissbort Thilo , Weidendorfer Daniel , Dietzel Martin , Dingwell Donald B.
Published: August 2023

We report the first calorimetric observations of glass transition temperatures and crystallization rates of anhydrous, amorphous calcium-magnesium carbonate using fast scanning differential scanning calorimetry. Hydrous amorphous Ca
0.95
Mg
0.05
CO
3
 · 0.5H
2
O (ACMC) solid was precipitated from a MgCl
2
–NaHCO
3
buffered solution, separated from the supernatant, and freeze-dried. An aliquot of the freeze-dried samples was additionally dried at 250°C for up to 6 h in a furnace and in a high-purity N
2
atmosphere to produce anhydrous ACMC. The glass transition temperature of the anhydrous Ca
0.95
Mg
0.05
CO
3
was determined by applying different heating rates (1000–6000 K s
−1
) and correcting for thermal lag to be 376°C and the relaxational heat capacity was determined to be
C
p = 0.16 J/(g K). Additionally, the heating rate dependence of the temperature that is associated with the corrected crystallization peaks is used to determine the activation energy of crystallization to be 275 kJ mol
−1
. A high-resolution transmission electron microscopy study on the hydrous and anhydrous samples provided further constraints on their compositional and structural states.

This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.
Comparison of the therapeutic efficacy of antibiotic-loaded polymeric tissue scaffold and bone cement in the regeneration of infected bone tissue
Authors: Konya Petek Şarlak , Konya Mehmet Nuri , Yılmaz Bilge Kağan , Kaga Elif , Kaga Sadık , Çetinkol Yeliz
Published: August 2023

Background

Local antibiotic applications have been used in osteomyelitis as an adjunctive treatment method. Biodegradable materials are also used for the same purpose by adding antibiotics. The fact that it does not require additional surgery to be removed is an important advantage. The current study is therefore intended to develop a biodegradable drug-loaded polymeric scaffold with a good antibiotic release that can be an alternative to antibiotic-impregnated bone cement.

Methods

A tissue scaffold containing poly (2-hydroxyethyl methacrylate) (PHEMA) was prepared in our laboratory and loaded with Ertapenem and Daptomycin(E&D) antibiotics.

To evaluate drug release kinetics, the absorbance values of the scaffold loaded with E&D were measured with the spectrometer.

For microbiological tests, (E&D) impregnated cement and scaffold, as well as the control scaffold and cement samples were investigated for their antibacterial activities on Staphylococcus aureus and Klebsiella pneumoniae strains using the disc diffusion method.

Results

The Daptomycin zone diameter in S. aureus ATCC strain was 17 mm, 24 mm for scaffold, and 22 mm for cement. Scaffold was found to be more effective than cement against S. aureus strain. On K. pneumoniae ATCC strain, it was found that this strain was resistant to Ertapenem, but the zone diameter was 21 mm for scaffold and 20 mm for cement. Ertapenem-loaded scaffold was found to be more effective than cement.

When we evaluated the release profiles, for the Daptomycin-loaded cement group, 98%of Daptomycin was cumulatively released within 30 min, and for the Daptomycin-loaded scaffold group, 100%of Daptomycin was cumulatively released in 6 days. To compare Ertapenem- loaded cement and scaffold, 98% of Ertapenem was cumulatively released within 10 min in the cement group. For the scaffold group, 100% of Ertapenem was cumulatively released in 17 days. It was found that e scaffold released the antibiotic more slowly and for a longer duration.
Phenotypic plasticity of antibiotic resistance, metabolism byproduct utilization and the evolution of mutually beneficial cooperation inEscherichia coli
Authors: Ye Nan , Hou Beibei , Song Jianxiao , Dunn Derek W , Ma Zhanshan (Sam) , Wang Rui-Wu
Published: August 2023

Although tag-based donation and recognition have well explained how the cooperative individuals are positively assorted if the cooperative individuals possess some signals and are also able to detect such signals, an additional mechanism is required to explain why some individuals pay the costs of evolving such a tag that may not be rewarded subsequently, and how such tag-based cooperative individuals will meet other similar individuals with a very low mutation rate. Here, we show that many and even allEscherichia colibacteria cells in the increased antibiotic concentration will plastically evolve to be antibiotic resistant individuals who could protect antibiotic sensitive strain from the attack of antibiotics, and the antibiotic resistant strain could reversibly evolve to be antibiotic sensitive in non-antibiotic supplement medium but in a harsher environment with low glucose. A further experiment showed that antibiotic-sensitiveE. colistrain could in turn help reduce the concentration of indole produced by the resistant strain. This metabolic product is harmful to the growth of the antibiotic-resistant strain but benefits the antibiotic-sensitive strain by helping turn on the multi-drug exporter to discharge the antibiotic. The utilization of metabolism byproduct indole produced by antibiotic-resistant cells benefits antibiotic-sensitive cells, while the indole-absorbing service of antibiotic sensitive cells unconsciously help in nullifying the indole side effect on antibiotic resistant strain, and a mutual benefit cooperation could therefore evolve.
Disentangling the spinal mechanisms of illusory heat and burning sensations in the Thermal Grill Illusion
Authors: Mitchell Alexandra G. , Ehmsen Jesper Fischer , Christensen Daniel Elmstrøm , Stuckert Anna Villaume , Haggard Patrick , Fardo Francesca
Published: August 2023

The Thermal Grill Illusion (TGI), a phenomenon in which the juxtaposition of innocuous warm and cold temperatures on the skin elicits a burning sensation, offers a unique perspective to how pain occurs in response to harmless stimuli. We investigated the role of the spinal cord in the generation of the TGI across two experiments (total n = 80). We applied heat and cold stimuli to dermatomes, areas of skin innervated by a single spinal nerve, that mapped onto adjacent or nonadjacent spinal segments. Enhanced warm and burning ratings during the TGI were observed when cold and warm stimuli were confined within the same dermatome. Further, we found the spatial organisation of warm and cold stimuli within and across dermatomes affected TGI perception. Perceived warmth and burning intensity increased when the cold stimulus projected to the segment more caudal to the warm stimulus, whilst perceived cold during the TGI decreased, compared to the opposite spatial arrangement. This suggests the perception of TGI is enhanced when cold afferents are projected to spinal segments positioned caudally in relation to those receiving warm afferents. Our results indicate distinct interaction of sensory pathways based on the segmental arrangement of afferent fibres and are consistent with current interpretations of the spread and integration of thermosensory information along the spinal cord.
Human plasma cells engineered to secrete bispecifics drive effectivein vivoleukemia killing
Authors: Hill Tyler F. , Narvekar Parnal , Asher Gregory , Camp Nathan , Thomas Kerri R. , Tasian Sarah K. , Rawlings David J. , James Richard G.
Published: August 2023

Bispecific antibodies are an important tool for the management and treatment of acute leukemias. Advances in genome-engineering have enabled the generation of human plasma cells that secrete therapeutic proteins and are capable of long-termin vivoengraftment in humanized mouse models. As a next step towards clinical translation of engineered plasma cells (ePCs) towards cancer therapy, here we describe approaches for the expression and secretion of bispecific antibodies by human plasma cells. We show that human ePCs expressing either fragment crystallizable domain deficient anti-CD19 x anti-CD3 (blinatumomab) or anti-CD33 x anti-CD3 bispecific antibodies mediate T cell activation and direct T cell killing of specific primary human cell subsets and B-acute lymphoblastic leukemia or acute myeloid leukemia cell linesin vitro. We demonstrate that knockout of the self-expressed antigen, CD19, boosts anti-CD19 bispecific secretion by ePCs and prevents self-targeting. Further, anti-CD19 bispecific-ePCs elicited tumor eradicationin vivofollowing local delivery in flank-implanted Raji lymphoma cells. Finally, immunodeficient mice engrafted with anti-CD19 bispecific-ePCs and autologous T cells potently preventedin vivogrowth of CD19+acute lymphoblastic leukemia in patient-derived xenografts. Collectively, these findings support further development of ePCs for use as a durable, local delivery system for the treatment of acute leukemias, and potentially other cancers.

Key points

Using gene editing, we engineered human plasma cells that secrete functional bispecifics to target leukemia cells expressing CD19 or CD33

Engineered plasma cells secreting bispecifics suppress patient-derived leukemia in immunodeficient mice
Changes of cell-type diversity in the polyp-to-medusa metagenesis of the scyphozoan jellyfishAurelia coerulea(formerly sp.1)
Authors: Link Oliver , Jahnel Stefan M. , Janicek Kristin , Kraus Johanna , Montenegro Juan Daniel , Zimmerman Bob , Wick Brittney , Cole Alison G. , Technau Ulrich
Published: August 2023

The life cycle of most medusozoan cnidarians is marked by the metagenesis from the asexually reproducing sessile polyp and the sexually reproducing motile medusa. At present it is unknown to what extent this drastic morphological transformation is accompanied by changes in the cell type composition. Here, we provide a single cell transcriptome atlas of the cosmopolitan scyphozoanAurelia coeruleafocussing on changes in cell-type composition during the transition from polyp to medusa. Notably, this transition marked by an increase in cell type diversity, including an expansion of neural subtypes. We find that two families of neuronal lineages are specified by homologous transcription factors in the sea anemoneNematostella vectensisandAurelia coerulea, suggesting an origin in the common ancestor of medusozoans and anthozoans about 500 Myr ago. Our analysis suggests that gene duplications might be drivers for the increase of cellular complexity during the evolution of cnidarian neuroglandular lineages. One key medusozoan-specific cell type is the striated muscle in the subumbrella. Analysis of muscle fiber anatomy and gene expression raises the possibility that the striated muscles arise from a population of smooth muscle cells during strobilation. Although smooth and striated muscles are phenotypically distinct, both have a similar contractile complex, in contrast to bilaterian smooth and striated muscles. This suggests that inAurelia, smooth and striated muscle cells may derive from the same progenitor cells.

Teaser

Single cell transcriptome atlas across the jellyfish life cycle reveals emergence of novel medusa-specific cell types is associated with expression of medusa-specific paralogs.
Enhancing visual perceptual learning using transcranial electrical stimulation: transcranial alternating current stimulation outperforms both transcranial direct current and random noise stimulation
Authors: He Qing , Zhu Xinyi , Fang Fang
Published: August 2023

Diverse strategies can be employed to enhance visual skills, including visual perceptual learning (VPL) and transcranial electrical stimulation (tES). Combining VPL and tES is a popular method that holds promise for significant improvements in visual acuity within a short time frame. However, there is still a lack of comprehensive evaluation regarding the effects of combining different types of tES and VPL on enhancing visual function, especially with a larger sample size. In the present study, we recruited four groups of subjects (26 subjects each) to learn an orientation discrimination task with five daily training sessions. During training, subjects’ occipital region was stimulated by one type of tES (anodal transcranial direct current stimulation (tDCS), alternating current stimulation (tACS) at 10 Hz, high-frequency random noise stimulation (tRNS), and sham tACS) while performing the training task. We found that compared with the sham stimulation, both the high-frequency tRNS and the 10 Hz tACS facilitated VPL efficiently in terms of learning rate and performance improvement, while there was little modulatory effect in the anodal tDCS condition. Remarkably, the 10 Hz tACS condition exhibited superior modulatory effects to the tRNS condition, demonstrating the strongest modulation among the most commonly used tES types for further enhancing vision when combined with VPL. Our results suggest that alpha oscillations play a vital role in VPL. Our study provides a practical guide for vision rehabilitation.
Spatial landmark detection and tissue registration with deep learning
Authors: Ekvall Markus , Bergenstråhle Ludvig , Andersson Alma , Czarnewski Paulo , Olegård Johannes , Käll Lukas , Lundeberg Joakim
Published: August 2023

Spatial landmarks are crucial in describing histological features between samples or sites, tracking regions of interest in microscopy, and registering tissue samples within a common coordinate framework. Although other studies have explored unsupervised landmark detection, existing methods are not well-suited for histological image data as they often require a large number of images to converge, are unable to handle non-linear deformations between tissue sections, and are ineffective for z-stack alignment, other modalities beyond image data, or multimodal data. We address these challenges by introducing a new landmark detection and registration method, utilizing neural-network-guided thin-plate splines. Our proposed method is evaluated on a diverse range of datasets, demonstrating superior performance in both accuracy and stability compared to existing approaches.
Molecular fingerprints in the hippocampus of alcohol seeking during withdrawal
Authors: Pagano Roberto , Salamian Ahmad , Skonieczna Edyta , Wojtas Bartosz , Gielniewski Bartek , Harda Zofia , Cały Anna , Havekes Robbert , Abel Ted , Radwanska Kasia
Published: August 2023

Alcohol use disorder (AUD) is characterized by excessive alcohol seeking and use. Here, we investigated the molecular correlates of impaired extinction of alcohol seeking using a multidimentional mouse model of AUD. We distinguished AUD-prone and AUD-resistant mice, based on the presence of ≥ 2 or < 2 criteria of AUD and utilized RNA sequencing to identify genes that were differentially expressed in the hippocampus and amygdala of mice meeting ≥ 2 or < 2 criteria, as these brain regions are implicated in alcohol motivation, seeking, consumption and the cognitive inflexibility characteristic of AUD. Our findings revealed dysregulation of the genes associated with the actin cytoskeleton, including actin binding molecule cofilin, and impaired synaptic transmission in the hippocampi of mice meeting ≥ 2 criteria. Overexpression of cofilin in the polymorphic layer of the dentate gyrus (PoDG) inhibited ML-DG synapses, increased motivation to seek alcohol and impaired extinction of alcohol seeking, resembling the phenotype observed in mice meeting ≥ 2 criteria. Overall, our study uncovers a novel mechanism linking increased hippocampal cofilin expression with the AUD phenotype.

Abstract Figure
Mouse model of multiple sclerosis induced by disrupting vesicular transport in oligodendrocytes
Authors: Chow Chun Hin , Huang Mengjia , Rai Jayant , Harada Hidekiyo , Eide Sarah , Sun Hong-Shuo , Feng Zhong-Ping , Monnier Philippe P. , Okamoto Kenichi , Zhang Liang , Sugita Shuzo
Published: August 2023

Multiple Sclerosis is an autoimmune demyelination disorder with unknown etiology. Despite the myelin damage, the roles of myelinating oligodendrocytes in driving disease progression remain unknown. We hypothesize that disrupting vesicular transport in oligodendrocytes during adolescence will disrupt myelin integrity and causes neuroinflammation. By creating a mouse model of SNAP-23 conditional knockout in mature oligodendrocytes, we showed that impairment in vesicular trafficking in oligodendrocytes causes demyelination. Neuroinflammation with infiltration of peripheral immune T cells into the central nervous system was observed accompanied by demyelination. Mechanistically, SNAP-23 removal in oligodendrocytes caused abnormal axon-myelin structures and impaired myelin protein trafficking, both can contribute to autoimmune activation and demyelination. With our novel animal model, we propose that oligodendrocyte injury is an endogenous early event in triggering Multiple Sclerosis.

One-Sentence Summary

Impaired vesicular transport in oligodendrocytes in adults caused demyelination and inflammation driving Multiple Sclerosis
G1/S Boundary Activates Interferon and Inflammatory Response Genes
Authors: Büyükkahraman Gözde , Kim Tae Hoon
Published: August 2023

Interferons (IFNs) have various roles in antiviral immunity, including curbing the immune system to prevent tissue damage and stimulating adaptive immunity. Due to its protective and destructive properties, IFN expression is tightly regulated. In contrast to its tight regulatory control, IFN expression is highly heterogeneous across many cell types upon pathogenic stimulus. The basis for this heterogenous IFN expression remains incompletely understood. Using single cell RNA-sequencing upon viral infection, we found that interferon expression is upregulated specifically in the late G1 phase of the cell cycle, and cell synchronization at the G1/S boundary boosts interferon expression. Furthermore, cell cycle arrest without any additional stimulus is sufficient to upregulate interferons and hundreds of other inflammatory response genes. Interferon upregulation at the G1/S boundary is cell type specific and not observed in non-immune cell types. Finally, we use ATAC-seq to identify potential transcription factors orchestrating this response. Together, these results uncover the cell cycle as a critical regulator of IFN expression in immune cells.
Hist2Vec: Kernel-Based Embeddings for Biological Sequence Classification
Authors: Ali Sarwan , Mansoor Haris , Chourasia Prakash , Patterson Murray
Published: August 2023

Biological sequence classification is vital in various fields, such as genomics and bioinformatics. The advancement and reduced cost of genomic sequencing have brought the attention of researchers for protein and nucleotide sequence classification. Traditional approaches face limitations in capturing the intricate relationships and hierarchical structures inherent in genomic sequences, while numerous machine-learning models have been proposed to tackle this challenge. In this work, we propose Hist2Vec, a novel kernel-based embedding generation approach for capturing sequence similarities. Hist2Vec combines the concept of histogram-based kernel matrices and Gaussian kernel functions. It constructs histogram-based representations using the uniquek-mers present in the sequences. By leveraging the power of Gaussian kernels, Hist2Vec transforms these representations into high-dimensional feature spaces, preserving important sequence information. Hist2Vec aims to address the limitations of existing methods by capturing sequence similarities in a high-dimensional feature space while providing a robust and efficient framework for classification. We employ kernel Principal Component Analysis (PCA) using standard machine-learning algorithms to generate embedding for efficient classification. Experimental evaluations on protein and nucleotide datasets demonstrate the efficacy of Hist2Vec in achieving high classification accuracy compared to state-of-the-art methods. It outperforms state-of-the-art methods by achieving > 76% and > 83% accuracies for DNA and Protein datasets, respectively. Hist2Vec provides a robust framework for biological sequence classification, enabling better classification and promising avenues for further analysis of biological data.
Characterizing the impact and maintenance of specialized toxin tolerance in a generalist species
Authors: Kropelin Grace , Scott Chialvo Clare H.
Published: August 2023

Understanding how plant-herbivore interactions can drive coevolution is a central goal of ecology and evolutionary biology. Of particular interest are the defenses produced by host plants/fungi and their impact on herbivore feeding strategies. In theimmigrans-tripunctataradiation ofDrosophila, mushroom-feeding species are classified as generalists, but their acceptable hosts include deadlyAmanitaspecies. In this study, we used behavioral assays to assess whether the mushroom-feeding speciesDrosophila guttiferais becoming a specialist and to characterize the impact of competition on host usage. We conducted feeding assays to confirm the presence of cyclopeptide toxin tolerance. We then completed host preference assays in female flies and larvae and did not find a preference for toxic mushrooms in either. Finally, we assessed the effect of competition on oviposition preference. We found that the presence of a competitor’s eggs on the preferred host was associated with the flies increasing the number of eggs laid on the toxic mushrooms. Our results suggest that an adaptation associated with specialized feeding behavior is not altering host usage and that competition plays a role in maintaining this trait. More broadly our work highlights how access to a low competition host resource helps to maintain adaptations with fitness costs.