bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Pronged Intracellular Co‐Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy
Authors: Meng Junli , Zhang Peisen , Chen Qizhe , Wang Zihua , Gu Yuan , Ma Jie , Li Wang , Yang Chen , Qiao Yuanyuan , Hou Yi , Jing Lihong , Wang Yong , Gu Zi , Zhu Lichong , Xu Haozhen , Lu Xueguang , Gao Mingyuan
Published: April 2022

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co‐delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid‐coated iron oxide nanoparticle is delivered as nanovaccine (IONP‐C/O@LP) that can co‐deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome‐mediated endocytosis. Such two‐pronged cellular uptake pattern enables IONP‐C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP‐C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen‐specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen‐specific immune responses in vivo.
Nanoscale Electrical Investigation of Transparent Conductive Electrodes Based on Silver Nanowire Network
Authors: Pham Sy Hieu , Ferri Anthony , Da Costa Antonio , Mohan M. M. Saj , Tran Van Dang , Nguyen Duy Cuong , Viville Pascal , Lazzaroni Roberto , Desfeux Rachel , Leclère Philippe
Published: April 2022

Presently, metallic nanowires (NWs) are the most promising materials to fabricate flexible transparent electrodes as an alternative to indium tin oxide. Here, the high performance of transparent conductive electrodes (TCEs) based on silver nanowires (AgNWs) percolation networks is reported. With optimized experimental conditions for the deposition, the AgNWs result in low sheet resistance of 10 Ω sq−1 combined with a high optical transmittance of 92.6% at λ = 550 nm. This leads to a valuable figure of merit as compared to other TCEs. In this study, the nanoscale electrical properties of the AgNWs are measured via conductive atomic force microscopy to characterize the percolation network. The electrical resistivity value calculated for a single AgNW is found to be about 12.35 µΩ cm, while a nanoscale conductivity map over an AgNW network bridging two electrodes has revealed high levels of current within the network over a distance of more than 1000 µm. The favorable determined conductivity results along with the high optical properties of the AgNWs network strongly suggest that thin‐film electrodes based on AgNWs will be a potential approach for future flexible electronic devices.
Mechano‐Chromic Photonic Crystals with Substrate‐Independent Brilliant Colors for Visual Sensing and Anti‐Counterfeiting Applications
Authors: Li Ang , Yang Dongpeng , Cao Cong , Hu Yang , Huang Shaoming
Published: April 2022

The mechano‐chromic photonic crystals (MPCs) show self‐restricted applications because they only exhibit bright reflective color on the black substrates but dim, complex, or white colors on substrates with different colors due to the superposition of incoherent scattering of light from MPCs and substrates. Herein, MPCs with substrate‐independent brilliant reflective colors, highly ordered structures, and superior mechano‐chromic performances are fabricated through the co‐assembly of same size silica and silica‐polydopamine (PDA) particles into the polymers. The silica‐PDA particles can efficiently absorb the harmful incoherent scattering of lights but show negligible effects on the long‐range order and thus endow MPCs with highly brilliant colors regardless of substrates. Compared to conventional MPCs, the as‐fabricated MPCs exhibit brilliant reflective colors on the white substrates at relaxing and stretching states, showing their great potential as real visual sensors. Moreover, based on the characteristics of MPCs, double‐layer photonic patterns with the color‐independent properties of each side at pristine states, showing diverse changes of colors on both sides upon stretching, are prepared and can be used for anti‐counterfeiting.
Communication practices of parents and unaffected sibling needs in families impacted by a diagnosis of Angelman syndrome
Authors: Turnwald Abigail , Thompson Talia , Nori Kelly , Duis Jessica
Published: April 2022

Angelman syndrome (AS) is a rare neurodevelopmental condition affecting approximately 1 in 15,000 individuals. To date, limited research elucidates how parents communicate about AS with unaffected siblings and their needs. This study aimed to understand if, when, and what parents are communicating with unaffected siblings. The study also evaluated unaffected siblings' knowledge of AS and their perceptions of their siblings with AS. Recruitment took place through social media platforms and a multidisciplinary Chromosome 15 clinic. Families were eligible for the study if they had a child diagnosed with AS and at least one unaffected sibling age five years or older. Two novel surveys, one for the parent and one for each of the unaffected siblings, were created based on a detailed literature review and input from AS professionals. Eighty‐two families met the criteria and completed the required surveys. The majority of parents (94%) discussed AS with the unaffected siblings, but despite these discussions 41% of unaffected siblings still had unanswered questions. This study highlights the need for improved communication between parents and the unaffected siblings and emphasizes the importance of educational materials for unaffected siblings.
Recent Trends in Nickel‐Catalyzed C−S Bond Formation
Authors: Kanchana U. S. , Diana Elizabeth J. , Mathew Thomas V.
Published: April 2022

Recently, sulphur containing molecules have witnessed significant recognition due to their wide application in various fields. In this regard, the synthesis of such C−S containing moieties has become a distinguished and omnipresent research sector in organic chemistry. The transition metal catalysts have been widely utilized in this field for the C−S bond formation. Among them, nickel catalysts have attracted great attention owing to their relatively lower toxicity, highly economical, plentiful and efficient metal which come up as a substitute for toxic and expensive 4d and 5d transition metals. The latest advancement in nickel‐catalyzed C−S bond making reactions are reviewed and covers literature from 2015–2021.
A review of the function and evolution of the cecal appendix
Authors: Smith Heather F.
Published: April 2022

Since its initial discovery in the 1500s, the cecal appendix has been an anatomical structure of great intrigue, notorious for its inconvenient tendency to become inflamed and often require surgical intervention. Appendicitis is one of the most common indications for emergency abdominal surgery, costing healthcare systems billions of dollars globally and causing tens of thousands of deaths annually. Yet, recent studies have indicated that the appendix may serve important protective functions in fortifying the body's immune response against invading pathogens and re‐inoculating the gut with commensal bacteria after periods of gastrointestinal illness. While the cecal appendix was once believed to be a synapomorphy of hominoids (humans and other great apes), recent studies suggested that it is a recurrent trait found in several other species of primates, rodents, lagomorphs, marsupials, and monotremes. Mapping appendiceal and other gastrointestinal traits across a mammalian consensus phylogeny revealed that the cecal appendix has evolved independently numerous times throughout mammalian evolution, significantly more than would be expected due to chance alone, suggesting that the appendix is adaptively advantageous. However, attempts to identify an overarching ecological, behavioral, dietary, or environmental factor driving some species to evolve an appendix have been largely unsuccessful, indicating that the cecal appendix has a complex and diverse evolutionary history. This review discusses the current understanding of the pathophysiology, evolution, and possible functions of the appendix, both within humans and broadly across the class Mammalia.
Development of highly selective fluorescent ferrocenyl‐iminopyridine chemosensor for biologically relevant Fe3+
Authors: Sharma Himani , Singh Vaishali , Tamrakar Arpna , Nigam Kamlesh Kumar , Pandey Mrituanjay D. , Tiwari Kamal Kant , Pandey Rampal
Published: April 2022

Design, synthesis, characterization, and ion detection studies of two ferrocene‐appended Schiff bases namely N‐(2‐[ferrocenylamino]ethyl)‐5‐nitropyridin‐2‐amine (1) and ferrocenylamino‐1H‐imidazole‐4‐carboxamide (2) been reported. Both the chemosensors have been thoroughly characterized using Fourier transfer infrared, 1H and 13C nuclear magnetic resonance, high resolution mass spectrometry, and ultraviolet/visible (UV/visible) and fluorescence spectral techniques. Probes 1 and 2 were designed with the aim of appending the ferrocenyl group with pyridine ring having an amine substitution (for 1) and imidazole ring with an amide substitution (for 2). Interaction of these probes with a series of cations and anions was examined through UV/vis and fluorescence spectral techniques. Probe 2 exhibited an insignificant response towards anions and loss of selectivity for cations, whereas 1 displayed highly selective detection towards biologically important Fe3+ in 2:1 (probe:cation) stoichiometry. Notably, none of the cations and anions could interfere the selectivity of Fe3+ ensured by 1 in aqueous medium. The limit of detection for Fe3+ detection using 1 was determined to be 0.2 ppm. The results strongly suggest that 1 could find promising future application as a chemosensor for Fe3+ in biological systems for quantification and qualitative analysis.
“You are not alone”: Connecting through a bereaved parent mentor program for parents whose child died of cancer
Authors: McNeil Michael J. , Kiefer Ashley , Woods Cameka , Barnett Brittany , Berry‐Carter Kathryn , Clark Lisa , Mandrell Belinda N. , Snaman Jennifer , Kaye Erica C. , Baker Justin N.
Published: April 2022

Background

Bereavement after the death of a child is devastating and associated with worse physical and psychosocial well‐being in parents. Evidence suggests that parents desire and benefit from support provided by other bereaved parents. To foster this peer support, an institutional peer‐to‐peer mentorship program for bereaved parents was established, through which trained bereaved parent mentors offer support for newly bereaved parents.

Methods

Using a retrospective cohort design, we describe the characteristics of participants of the Bereaved Parent Mentorship program. Trained bereaved parent mentors documented encounters with newly bereaved parent mentees using a secure internet‐based form. Mentors summarized each encounter including any concerns or need for professional psychosocial support. Descriptive statistics were used to describe mentor and mentee characteristics; free text from encounter summaries was qualitatively analyzed using content analysis.

Results

A total of 1368 documented encounters occurred between 150 mentees and 39 mentors from January 1, 2014 to February 29, 2020. Only seven encounters (0.5%) were flagged as serious concern necessitating professional psychosocial support. Four key themes in the encounters between mentors and mentees emerged, including: descriptions of the grief experience, ways in which a mentor supported their mentee, challenges the mentor experienced in supporting the mentee, and personal benefit gained by the mentor from supporting their mentee.

Conclusion

This structured Bereaved Parent Mentorship program fostered rich interactions between bereaved parent participants, with very few encounters requiring professional assistance. Future research will assess the impact of bereaved mentor programs on resilience and psychosocial, physical, and functional well‐being of parents.
An Adaptive Auto‐Synthesizer using Online PAT Feedback to Flexibly Perform a Multistep Reaction
Authors: Liu Junliang , Sato Yusuke , Yang Fan , Kukor Andrew J. , Hein Jason E.
Published: April 2022

Automated chemical synthesizers have become more common in recent years but struggle to apply rigid procedures to broad substrate scopes. We have developed an adaptive auto‐synthesizer that uses online HPLC and FTIR measurements to adapt to the changing reactivities of different substrates, allowing precise control of reaction conditions. To do so, we designed a flexibly‐timed procedure consisting of specific actions performed by our platform when specific reaction‐monitoring checkpoints are met. Online HPLC allowed our system to autonomously separate, label and quantify most reaction components, with orthogonal FTIR enabling non‐UV active species to be additionally tracked. We tested our platform with CDI‐mediated multistep amidation reactions using a variety of different acid and amine substrates. To demonstrate the high reproducibility and control afforded by our system, we determined the relative rates of both acid activation and subsequent amidation, providing insight into substrate reactivities and the reaction mechanism.
Aromatase inhibitors and the incidence of Parkinson disease: A population‐based cohort study
Authors: Khosrow‐Khavar Farzin , Azoulay Laurent , Montastruc Jean‐Louis , Montastruc François , Renoux Christel
Published: April 2022

Background

Current guidelines recommend the treatment of hormone receptor–positive breast cancer with aromatase inhibitors (AIs) and tamoxifen in the adjuvant setting. Some observational studies have raised concerns that tamoxifen may be associated with an increased risk of Parkinson disease (PD). However, no studies have directly compared the risk of PD between AIs and tamoxifen in women diagnosed with breast cancer.

Methods

Using the UK Clinical Practice Research Datalink, the authors assembled a cohort of women newly diagnosed with breast cancer and newly treated with either AIs or tamoxifen between January 1, 1995, and December 31, 2017. Patients were followed 1 year after treatment initiation (ie, a 1‐year lag) until an incident diagnosis of PD or were censored at death from any cause, the date of transfer out of the practice, or the end of the study period (December 31, 2018). Cox proportional hazards models with inverse probability of treatment weights were used to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for PD comparing AIs with tamoxifen and accounting for more than 30 confounders.

Results

In all, 30,140 women with nonmetastatic breast cancer were identified: 13,838 initiated AIs, and 16,302 initiated tamoxifen. Compared with tamoxifen, AIs were not associated with an increased risk of PD (HR, 0.94; 95% CI, 0.60‐1.47). Consistent results were observed across all secondary and sensitivity analyses.

Conclusions

In this large observational study, the use of AIs, in comparison with tamoxifen, was not associated with an increased risk of PD in women diagnosed with nonmetastatic breast cancer in a real‐world setting.

Lay Summary

Previous studies have indicated that tamoxifen may increase the risk of Parkinson disease in the treatment of breast cancer.

However, no studies have directly compared the risk of Parkinson disease between aromatase inhibitors and tamoxifen.

This study included 30,140 women diagnosed with breast cancer and treated with aromatase inhibitors or tamoxifen.

Overall, compared with tamoxifen, aromatase inhibitors were not associated with an increased risk of Parkinson disease in women diagnosed with breast cancer.

This study provides an important addition to the comparative safety profile of aromatase inhibitors and tamoxifen in the treatment of breast cancer.
Peripheral blasts are associated with responses to ruxolitinib and outcomes in patients with chronic‐phase myelofibrosis
Authors: Palandri Francesca , Bartoletti Daniela , Iurlo Alessandra , Bonifacio Massimiliano , Abruzzese Elisabetta , Caocci Giovanni , Elli Elena M. , Auteri Giuseppe , Tiribelli Mario , Polverelli Nicola , Miglino Maurizio , Heidel Florian H. , Tieghi Alessia , Benevolo Giulia , Beggiato Eloise , Fava Carmen , Cavazzini Francesco , Pugliese Novella , Binotto Gianni , Bosi Costanza , Martino Bruno , Crugnola Monica , Ottaviani Emanuela , Micucci Giorgia , Trawinska Malgorzata M. , Cuneo Antonio , Bocchia Monica , Krampera Mauro , Pane Fabrizio , Lemoli Roberto M. , Cilloni Daniela , Vianelli Nicola , Cavo Michele , Palumbo Giuseppe A. , Breccia Massimo
Published: April 2022

Background

The presence of peripheral blasts (PB) is a negative prognostic factor in patients with primary and secondary myelofibrosis (MF) and PB ≥4% was associated with a particularly unfavorable prognosis. Ruxolitinib (RUX) is the JAK1/2 inhibitor most used for treatment of MF‐related splenomegaly and symptoms. Its role has not been assessed in correlation with PB.

Methods

In 794 chronic‐phase MF patients treated with RUX, we evaluated the impact of baseline percentage of PB on response (spleen and symptoms responses) and outcome (RUX discontinuation‐free, leukemia‐free, and overall survival). Three subgroups were compared: PB‐0 (no PB, 61.3%), PB‐4 (PB 1%‐4%, 33.5%), and PB‐9 (PB 5%‐9%, 5.2%).

Results

At 3 and 6 months, spleen responses were less frequently achieved by PB‐4 (P = .001) and PB‐9 (P = .004) compared to PB‐0 patients. RUX discontinuation‐free, leukemia‐free, and overall survival were also worse for PB‐4 and PB‐9 patients (P = .001, P = .002, and P < .001, respectively).

Conclusions

Personalized approaches beyond RUX monotherapy may be useful in PB‐4 and particularly in PB‐9 patients.
Solvophobically‐Driven Merocyanine Dye Assembly: Predominant Dipole‐Dipole Interactions Over Hydrogen‐Bonding
Authors: Rajak Aritra , Kumar Singh Ajeet , Roy Lisa , Das Anindita
Published: April 2022

Merocyanine dye assembly in nonpolar solvents is driven by electrostatic dipole‐dipole interactions, which make hierarchical structures of merocyanine less favorable, due to the compensation of its dipole moment in the discrete antiparallel dimer state. Herein, we describe the self‐assembly of a merocyanine dye (MC−OH) into higher aggregates in aqueous medium (with 10% dioxane) by synergistic effect of dipole‐dipole interactions and strong dispersion forces, which remains underexplored for its known molecular stabilization in polar solvents. Our results reveal that in the crystal packing, strong intermolecular hydrogen (H)‐bonding predominates over the dipole‐dipole interactions, which confines the dye into a head‐to‐head parallel π‐stacked assemblage. When intermolecular H‐bonding in water is curtailed, antiparallel dimers by dipolar interactions become predominant. Several of these antiparallel dimers laterally cluster through solvophobically‐induced π‐stacking and form stable nanodiscs, which exhibit efficient hydrophobic dye sequestering properties. At higher concentration, the nanodiscs are transformed into elongated nanotapes. The computational studies support the experimental findings and emphasize the competing nature of multiple noncovalent interactions in guiding the dye assembly under different conditions.
The influence of plasma evolution on a kinetic scenario of plasma collisional relaxation
Authors: Erofeev V.I.
Published: April 2022

A reduction of the two‐time formalism [V. I. Erofeev, Journal of Plasma Physics 85, 905850104 (2019)] to a highly informative scenario of redistribution of plasma particles in momentum due to Coulomb collisions is reported. The standard case of an ideal classical ionized homogeneous plasma is considered. It is found that the leading‐order approximation of the scenario is consistent with the well‐known Lenard–Balescu Equation [A. Lenard, Ann. Phys. 10, 390–400 (1960); R. Balescu, Phys. Fluids 3, 52–63 (1960)]. A correction to the collision integral of this equation is developed to account for the time variation of plasma parameters. This correction is shown to differ from its analogs related to the existing generalizations of the Lenard–Balescu kinetic equation [Yu.L. Klimontovich, Kinetic theory of nonideal gases and nonideal plasmas (Pergamon Press, Oxford [1982]); V.V. Belyi, Yu.A. Kukharenko, J. Wallenborn, Journal of plasma physics 59, 657–669 (1998)].
Sex differences and modifiable dementia risk factors synergistically influence memory over the adult lifespan
Authors: LaPlume Annalise A. , McKetton Larissa , Anderson Nicole D. , Troyer Angela K.
Published: April 2022

Introduction

More women than men develop Alzheimer's disease, yet women perform better and show less decline on episodic memory measures, a contradiction that may be accounted for by modifiable risk factors for dementia.

Methods

Associations among age, sex, modifiable dementia risk factors, and cognition were measured in a cross‐sectional online sample (n = 21,840, ages 18 to 89).

Results

Across four tests of associative memory and executive functions, only a Face‐Name Association task revealed sex differences in associative memory that varied by age. Men had worse memory than women (the equivalent of performing similar to someone 4 years older) across ages. Men had larger age differences than women (ie, worse memory in older ages) among people with no to one risk factor, but not those with multiple risk factors.

Discussion

Because the relationship between dementia risk factors and age‐related memory differences varies between men and women, sex‐specific dementia prevention approaches are warranted.
Disturbance decreases genotypic diversity by reducing colonization: Implications for disturbance–diversity feedbacks
Authors: Kollars Nicole M. , Stachowicz John J.
Published: April 2022

One objective of eco‐evolutionary dynamics is to understand how the interplay between ecology and evolution on contemporary timescales contributes to the maintenance of biodiversity. Disturbance is an ecological process that can alter species diversity through both ecological and evolutionary effects on colonization and extinction dynamics. While analogous mechanisms likely operate among genotypes within a population, empirical evidence demonstrating the relationship between disturbance and genotypic diversity remains limited. We experimentally tested how disturbance altered the colonization (gain) and extinction (loss) of genets within a population of the marine angiosperm Zostera marina (eelgrass). In a 2‐year field experiment conducted in northern California, we mimicked grazing disturbance by migratory geese by clipping leaves at varying frequencies during the winter months. Surprisingly, we found the greatest rates of new colonization in the absence of disturbance and that clipping had negligible effects on extinction. We hypothesize that genet extinction was not driven by selective mortality from clipping or from any stochastic loss resulting from the reduced shoot densities in clipped plots. We also hypothesize that increased flowering effort and facilitation within and among clones drove the increased colonization of new genets in the undisturbed treatment. This balance between colonization and extinction resulted in a negative relationship between clipping frequency and net changes in genotypic richness. We interpret our results in light of prior work showing that genotypic diversity increased resistance to grazing disturbance. We suggest that both directions of a feedback between disturbance and diversity occur in this system with consequences for the maintenance of eelgrass genotypic diversity.
Enzymatic removal of sialic acid enables iCIEF stability monitoring of charge variants of a highly sialylated bispecific antibody
Authors: Peters Björn‐Hendrik , Bautista James , Slaney Thomas R. , Guo Hongyue , Huang Richard Y.‐C. , Krause Mary E. , Zeng Ming , Cheng Julie , Chen Zhi
Published: April 2022

Antibody‐based therapeutic proteins have highly complex molecular structures. The final therapeutic protein product may contain a wide range of charge variants. Accurate analysis of this charge variant composition is critical to determine manufacturing process consistency and protein stability and ultimately helps to ensure that patients receive a safe and efficacious product. Here, a highly sialylated bispecific antibody (bsAb‐1) challenged the ability to monitor stability by imaged capillary isoelectric focusing (iCIEF). This challenge was overcome by optimization of the iCIEF master mix buffer (adjustment of urea concentration, addition of l‐arginine) and enzymatic removal of sialic acid. The method was qualified by assessing linearity, precision, LOD, LOQ, accuracy, and robustness in accordance with ICH guidance. Main species loss detectability increased up to approximately fivefold compared to the iCIEF method without desialylation when monitoring changes in stressed samples. Importantly, the results of the iCIEF method with desialylation correlated with results obtained through LC–MS tryptic peptide mapping and enabled analysis of formulation development stability samples. Finally, this analytical method shows the potential to assess low‐concentration formulation development samples down to a sample concentration of 0.1 mg/ml.
Anisotropic double‐Gaussian analytical wake model for an isolated horizontal‐axis wind turbine
Authors: Soesanto Qidun M. B. , Yoshinaga Tsukasa , Iida Akiyoshi
Published: April 2022

An anisotropic double Gaussian (DG) model for analytical wake modeling to predict the streamwise wake velocity behind an isolated non‐yawed horizontal‐axis wind turbine is proposed. The proposed model is based upon the conservation of mass and momentum inside a streamtube control volume. The wake growth rate parameters to distinguish the wake expansion rate between lateral and vertical directions were tuned based on numerical and measurement data of utility‐scale turbines. It was found that the proposed model can give feasible predictions within the full‐wake region under different inflow conditions. In addition, the other analytical models based on top‐hat shape and single Gaussian approaches were evaluated for comparison. The root‐mean‐square error statistical analysis was used to evaluate the performance of each examined model under different flow conditions. In general, the proposed model outperformed the other examined models in all wake region categories, particularly within the near‐wake region and the onset of the far‐wake region, which are beyond the scope of the conventional approach for analytical wake modeling. This advantage gives the potential for the proposed model to provide a better prediction for the wake flow estimation within tightly packed wind farms.
Effect of alfalfa substituted with ramie on the expression of apoptotic genes in the gastrointestinal tracts of goats
Authors: Liu Qian , Fu Chao , Yang Hai , Zhou Chuanshe , Kang Jinhe , Chen Liang , Kong Zhiwei , Tan Zhiliang , Tang Shaoxun
Published: April 2022

The study investigated the effect of alfalfa hay substituted with ramie silage on the expression of apoptotic genes in the gastrointestinal tract of goats. Thirty‐two goats were randomly allocated into four groups, in which the alfalfa was substituted with ramie at 0%, 35%, 75%, and 100% levels, respectively. In the rumen, the mRNA expression of Bax was significantly up‐regulated (p = .0007) when alfalfa was 100% substituted by ramie; the mRNA expression of Bcl‐2/Bax was significantly down‐regulated (p = .02) when alfalfa was 100% substituted by ramie compared with the 75% substituted treatment; the protein expression of Bcl‐xl was significantly down‐regulated (p = .03) when alfalfa was 100% substituted by ramie compared with 35% and 75% substituted treatments, respectively. In the jejunum, the mRNA expression of p53 was significantly up‐regulated (p = .01) when alfalfa was 100% substituted by ramie compared with 0% and 35% substituted treatments; the protein expression of p53 was significantly up‐regulated (p = .001) when alfalfa was 35% substituted by ramie compared with 0% and 75% substituted treatments. However, the activity of Caspase‐3 was not affected by different substituting levels of ramie in the rumen and jejunum of goats (p > .05). In conclusion, ramie with high substitution had strong antinutritional effect, which might promote the apoptosis in the gastrointestinal tract of goats in a caspase‐independent manner, thus affecting the growth and development of goat. It was suggested that ramie should not replace alfalfa more than 35% in the process of goat feeding.
The impact of increasing the United Kingdom national minimum wage on self‐reported health
Authors: Maxwell Jacob , Pryce Robert , Wilson Luke B.
Published: April 2022

There is a growing but mixed literature on the health effects of minimum wages. If minimum wage changes have a statistically significant impact on health, this suggests health effects should be incorporated into cost‐benefit analyses to capture wider policy impacts. Whilst most existing UK based literature examines the introduction of a minimum wage, this paper exploits the 2016, 2017 and 2018 UK National Minimum Wage (NMW) increases as natural experiments using a series of difference‐in‐differences models. Short Form‐12 (SF‐12) mental and physical component summary scores are used as dependent variables. In the base case and all sensitivity analyses, the estimated impact of NMW increases on mental and physical health are insignificant. The policy implication is that health effects should not be included in cost‐benefit analyses examining the NMW.
Src homology 3 domain binding kinase 1 protects against hepatic steatosis and insulin resistance through the Nur77–FGF21 pathway
Authors: Ahuja Palak , Bi Xinyi , Ng Chun Fai , Tse Margaret Chui Ling , Hang Miaojia , Pang Brian Pak Shing , Iu Elsie Chit Yu , Chan Wing Suen , Ooi Xin Ci , Sun Anqi , Herlea‐Pana Oana , Liu Zhixue , Yang Xiuying , Jiao Baowei , Ma Xin , Wu Kelvin Ka Lok , Lee Leo Tsz On , Cheng Kenneth King Yip , Lee Chi Wai , Chan Chi Bun
Published: April 2022

Background and Aims:

Metabolism in the liver is dysregulated in obesity, contributing to various health problems including steatosis and insulin resistance. While the pathogenesis of lipid accumulation has been extensively studied, the protective mechanism against lipid challenge in the liver remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity.

Approach and Results:

Enhanced Sbk1 expression was found in the liver of high‐fat diet (HFD)–induced obese mice and fatty acid (FA)–challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver‐specific SBK1 knockout (Lsko) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox (Fl/Fl) control mice when fed the HFD. The HFD‐fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high‐fructose diet–induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1‐overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism.

Conclusions:

Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77–FGF21 pathway.
Head and neck cancer organoids as a promising tool for personalized cancer therapy: A literature review
Authors: Mohtasham Nooshin , Mohajer Tehran Farnaz , Abbaszadeh Hamid
Published: April 2022

Background and Aim

Chemotherapy and targeted therapy are used in treating head and neck cancers (HNCs) either alone or in combination with surgery, especially in advanced tumors but these treatments have resulted in variable outcomes in different patients. This, along with the introduction of new therapies to improve the survival of patients makes it necessary to search for models that can predict the response to treatment among different patients. Organoids, as three‐dimensional culture models, have been studied more widely in non‐HNCs and to a lesser extent in HNCs as tools to predict treatment outcomes. We aimed to conduct a review to validate the use of organoids as a preclinical tool for the treatment of HNCs patients.

Methods

A comprehensive literature search was separately performed by both authors in PubMed and google scholar databases, using the following keywords: “organoid,” “head and neck cancer,” “personalized medicine,” “chemotherapy,” and “targeted therapy.” The articles published up to September 2021 were included in this review and selected according to a quality appraisal method.

Results

Examination of HNC‐derived organoids made in various studies showed that these organoids had the ability to recapitulate original tumor features, including histopathological properties, functional characteristics, and expression of molecular markers in almost all of the studies. Differential sensitivity to chemotherapy drugs similar to in vivo was observed in sensitivity testing. Epidermal growth factor receptor (EGFR) expression levels were different between organoids from different patients and EGFR expression level was found to correlate with the response to anti‐EGFR targeted therapy. A similar result was reported for organoids derived from salivary adenoid cystic carcinoma.

Conclusion

Since HNC‐derived organoids seem to recapitulate characteristics of original tumors and to show differential responses to different chemotherapy and targeted therapy agents, these organoids might have the potential to be used as preclinical prediction tools for the treatment of HNC patients.
Cross‐border insolvency in Hong Kong: Developments and updates
Authors: Yung Patrick
Published: April 2022

In recent years, particularly in 2020 and 2021, the Hong Kong High Court has been actively developing its common law framework in relation to the recognition of and assistance to foreign insolvency representatives. This article aims to provide an update to the common law recognition framework in Hong Kong and argues that the recent developments are intended to achieve two objectives, namely harmonizing the Hong Kong common law position with the relevant principles under the UNCITRAL Model Law on Cross‐border Insolvency; and strengthening the implementation of the mutual recognition framework on corporate insolvency proceedings between Mainland China and Hong Kong. This article also discusses how some of the unresolved issues in the Hong Kong common law recognition framework may be approached in light of these two objectives.
Introduction to a special section on the supervisee's perspective of reflective supervision/consultation
Authors: Barron Carla C. , Eaves Tanika
Published: April 2022

The definition and implementation of reflective supervision/consultation (RS/C) in the infant early childhood mental health field (IECMH) has largely been driven by expert supervisors, researchers, and leaders in the field. The voice of the frontline practitioner, the most likely recipient of RS/C has had less prominence in the scholarly discourse, leaving unclear supervisees’ perspectives on the meaning and value of RS/C. This special section addresses supervisees’ experiences with RS/C across five studies. In the first two papers, researchers examined supervisees’ perspectives on essential components of RS/C and perceived impacts of RS/C on their work. In paper 3, researchers report on perceived associations between RS/C and professionals’ well‐being. The fourth paper addresses experiences in RS/C and professionals’ use of reflective practices. Finally, researchers in the fifth paper present the psychometric properties of an observational tool that focuses on the interaction between supervisors and supervisees. Collectively, the studies promote understanding about supervisees’ perspectives and experiences that may benefit future research studies aimed at investigating the role of RS/C in well‐being and practice and provide information for program administrators considering the inclusion of RS/C in professional development efforts.
Guide to radiation therapy use in companion animals
Authors: Elliott James
Published: April 2022

Background: Radiation therapy (RT) is an important component of a multimodality approach to treating cancer in companion animals. Many owners that receive a cancer diagnosis for their pet never get to consult with a veterinary oncologist, and so it is important that clinicians involved in cancer diagnosis or treatment (whether a general practitioner, internal medicine clinician, surgical specialist or neurologist) have a basic understanding of the equipment used, the basic mechanism of action, the indications, as well as the expected side effects of RT.

Aim of the article: This article provides an updated review of veterinary RT. This is particularly timely, given the current investment in RT facilities in the UK, which will revolutionise the incorporation of RT into veterinary medicine in the near future.
Approach to generalised alopecia in dogs: use and abuse of endocrine testing
Authors: Cerundolo Rosario
Published: April 2022

Background: Alopecia can be a concerning discovery for owners to make in their dogs, as well as a frustrating and challenging condition for veterinary surgeons to investigate. However, successful management can be achieved by undertaking a methodical approach to correct diagnosis.

Aim of the article: This article guides veterinary surgeons through the diagnostic approach to generalised alopecia. Clinical cases have been included to help colleagues successfully manage similar scenarios without running unnecessary, often expensive, diagnostic tests.
Dealing with gastrointestinal disease in ferrets
Authors: Livingstone Madonna
Published: April 2022

Background: Ferrets have been domesticated for approximately 3000 years, yet many veterinary professionals feel unequipped to treat them. Since the 1980s, the worldwide increase in the popularity of ferrets as pets means that these curious creatures are being presented to general practice more frequently. As seen with cats and dogs, most ferret owners identify their pets as members of their family and, as such, they expect a high level of care from vets.

Aim of the article: This article encourages clinicians to realise that they can apply the same clinical skills to ferrets that they use on a daily basis to diagnose and treat causes of gastrointestinal disease in dogs and cats. Several species‐specific conditions will be covered, including conditions of the oral cavity, stomach and intestine.
Human health and safety in small animal veterinary anaesthesia
Authors: Powley Lucy
Published: April 2022

Background: Veterinary practice is a hazardous work environment with high levels of occupation‐related injuries and illness reported compared to general practitioners of human medicine (Nienhaus and others 2005). There are occupational hazards that veterinary staff may face when performing veterinary anaesthesia and so it's important to know how to minimise the risks.

Aim of the article: This article outlines the physical, biological, chemical and potential psychological hazards encountered in veterinary anaesthesia, and examines what can be done to minimise the risks to those involved.
Impact of maternal desvenlafaxine exposure on brain development in pregnant albino rats and their fetuses
Authors: Ahmed Sarah H. , El Ghareeb Abd El Wahab A. , El‐Rahman Heba Ali Abd , Almaaty Ali H. Abu
Published: April 2022

Depression during pregnancy adversely affects fetal development. Desvenlafaxine drug is used for the treatment of gestational depression. In light of the well‐established role of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in regulating neurogenesis and neural survival, the role of S100b in nerve cell energetic metabolism, differentiation of neurons and glial cells, an aberrant increase in NGF, BDNF and S100b expression in the fetal brain may contribute to desvenlafaxine cognitive disorders by altering brain development. This study is trying to determine the effect of desvenlafaxine on brain development. Thirty timed pregnant rats (from the 5th to the 20th day) were divided into three groups: control, low dose (5.14 mg/kg/day) and high dose (10.28 mg/kg/day) of desvenlafaxine where all animals received the corresponding doses by gavage. Maternal and fetal brain samples were fixed for histological, immunohistochemical (IHC) study of NGF and evaluated for BDNF and S100b genes expression. Desvenlafaxine induced some of the histopathological alterations in maternal and fetal rat brains. Moreover, IHC analysis of maternal and fetal rat brains showed that groups treated with desvenlafaxine demonstrated a significant increase of NGF protein immunoreactivity compared with that in the controls. Gene expression results revealed upregulation of messenger RNA BDNF and S100B expression. According to developmental changes in the brain, desvenlafaxine affects neonatal growth during pregnancy, which may lead to delay of brain development. So, it is essential to survey the roles of antidepressant drugs on neonatal development during pregnancy.
Plasma extracellular vesicle derived protein profile predicting and monitoring immunotherapeutic outcomes of gastric cancer
Authors: Zhang Cheng , Chong Xiaoyi , Jiang Fangli , Gao Jing , Chen Yang , Jia Keren , Fan Meng , Liu Xuan , An Jin , Li Jian , Zhang Xiaotian , Shen Lin
Published: April 2022

Immune checkpoint inhibitor (ICI)‐based immunotherapy brought new hope for gastric cancer (GC) treatment. However, due to the lack of proper biomarkers, patient selection and outcome prediction for GC's immunotherapy remain unsatisfying. In this study, through applying an extracellular vesicle (EV) protein expression array, we assessed the correlation of plasma EV‐derived protein spectrum with outcomes of ICI‐related therapeutic combinations. Plasma from 112 GC patients received ICI‐related therapies were investigated retrospectively/prospectively as three cohorts. We identified four plasma EV‐derived proteins (ARG1/CD3/PD‐L1/PD‐L2) from 42 crucial candidate proteins and combined them as an EV‐score that robustly predicting immunotherapeutic outcomes at baseline and dynamically monitoring disease progression along with treatment. High EV‐score reflected microenvironmental features of stronger antitumour immunity, characterized by more activated CD8+ T/NK cells, higher TH1/TH2 ratio and higher expressions of IFN‐γ/perforin/granzymes in paired peripheral blood, which were verified by dataset analysis and in vivo experiments. EV‐score≥1 GC received more therapeutic benefits from ICIs, while EV‐score < 1 GC potentially benefited more from ICIs combining HER2‐targeted therapies. Collectively, through proposing a plasma EV‐score on protein level that powerfully predicting and monitoring GC's immunotherapeutic outcomes, our work facilitated clinical patient selection and decision‐makings, and provided mechanistical insights for immunotherapy‐related microenvironmental changes and improvements for current ICI‐regimens.
Clearance of HIV-1 or SIV reservoirs by promotion of apoptosis and inhibition of autophagy: Targeting intracellular molecules in cure-directed strategies
Authors: Chen Min , Li Min , Budai Marietta M , Rice Andrew P , Kimata Jason T , Mohan Mahesh , Wang Jin
Published: April 2022

The reservoirs of the HIV display cellular properties resembling long-lived immune memory cells that could be exploited for viral clearance. Our interest in developing a cure for HIV stems from the studies of immunologic memory against infections. We and others have found that long-lived immune memory cells employ prosurvival autophagy and antiapoptotic mechanisms to protect their longevity. Here, we describe the rationale for the development of an approach to clear HIV-1 by selective elimination of host cells harboring replication-competent HIV (SECH). While reactivation of HIV-1 in the host cells with latency reversing agents (LRAs) induces viral gene expression leading to cell death, LRAs also simultaneously up-regulate prosurvival antiapoptotic molecules and autophagy. Mechanistically, transcription factors that promote HIV-1 LTR-directed gene expression, such as NF-κB, AP-1, and Hif-1α, can also enhance the expression of cellular genes essential for cell survival and metabolic regulation, including Bcl-xL, Mcl-1, and autophagy genes. In the SECH approach, we inhibit the prosurvival antiapoptotic molecules and autophagy induced by LRAs, thereby allowing maximum killing of host cells by the induced HIV-1 proteins. SECH treatments cleared HIV-1 infections in humanized mice in vivo and in HIV-1 patient PBMCs ex vivo. SECH also cleared infections by the SIV in rhesus macaque PBMCs ex vivo. Research efforts are underway to improve the efficacy and safety of SECH and to facilitate the development of SECH as a therapeutic approach for treating people with HIV.
Climate change impacts on phenology and ripening of cv. Touriga Nacional in the Dão wine region, Portugal
Authors: Rodrigues Pedro , Pedroso Vanda , Reis Samuel , Yang Chenyao , Santos João A.
Published: April 2022

The present study is devoted to climate change impact assessment on the phenological development and ripening of cv. Touriga Nacional in the Dão Wine Region, Portugal. For this purpose, the dates of the three main phenological stages (budbreak, flowering and veraison) and two maturity stages are projected for two future periods (2041–2070 and 2071–2100), under two anthropogenic radiative forcing scenarios (RCP4.5 and RCP8.5), and compared against a baseline period (1991–2020). The phenological and maturity stages are simulated using phenological development models (PDMs) and a temperature‐based ripeness model (TRM), respectively. An overall advancement in both phenology and ripening stages are identified under future warmer climates, though site‐dependent. Furthermore, the advancements in phenology are more pronounced (a) for stages between the beginning of veraison and end of ripening than for the earlier stages, (b) for the long‐term future period (2071–2100) under RCP8.5 and (c) for the vineyard site “Viseu.” These changes are due to the combination of budbreak advancement with a shortening of some phenophases. The strongest shortening is found in the ripening period, while no significant changes in flowering timings and duration of the berry development period are projected. The advancement and the shortening of the grapevine growing season will shift ripening to the warmest part of the year. This twofold climate change impact of the air temperature on ripening may affect the sugar and organic acid balance, as well as the colour of the must. The current findings can be used by the regional winemaking sector in planning and implementing suitable climate change adaptation to enhance its climate resiliency and sustainability. Subsequent studies for this wine region should be carried out to assess the climate change impacts on late frost risk, on climatic viticultural zoning, on yield and berry quality at harvest.