bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Four Cucumber Germplasm Genotypes, Grown in Qatar and the Indian Agro-climatic Zone, Based on Its Phenotypic Traits
Authors: Khan Muvin , Garg Amar Prakash , Jain Sourabh , Tanushiri .
Published: May 2023

This study included four genotypes of cucumber (IC257296, IC420405, GYNE-5, PUSA SANYOG) which were evaluated based on phenotypic traits when grown under two different soil zones of Doha (Qatar) and Meerut (India). Statistical analysis to estimate various genetic parameters like phenotypic and genotypic variance, phenotypic and genotypic coefficient of variation (PCV and GCV), broad sense heritability and genetic gain and principal component analysis (PCA) of genotypes was done in order to assess the magnitude of variability for various agro-metrical characters. In Indian soil zone, highest yield was observed in GYNE-5, while, in Qatar soil zone, highest yield was observed in PUSA SANYOG. The phenotypic coefficient of variation (PCV) was higher than its corresponding genotypic counterpart (GCV) for all characters studied. High broad-sense heritability was associated with all the traits in both zones except fruit length. Days to edible maturity, fruit length and fruit width showed low genetic gain in qatar zone; hence, heterosis breeding would be recommended. Principal  component analysis involved vine length and days to edible maturity as the most discriminating trait that accounted for greater variability in cucumber in qatar zone, and it should be considered in cucumber improvement programs. Correlation analysis represent that yield was positively correlated with fruit length and fruit width, while, fruit per plant showed positive significant correlation with vine length. Present findings suggest that PUSA SANYOG may be cultivated in other areas with similar climatic conditions. This study will help to improve the protected agriculture model of Qatar and revenue generation for the farmers.
An Inclusive Approach to Addiction Care—Helping the Helpers
Authors: Pollack Harold A. , Schneider John A. , Taxman Faye S.
Published: May 2023

This Viewpoint discusses the idea of helping the helpers, those who are supporters or caregivers to individuals with substance use disorder.
Cost-effectiveness of Increasing Buprenorphine Treatment Initiation, Duration, and Capacity Among Individuals Who Use Opioids
Authors: Claypool Anneke L. , DiGennaro Catherine , Russell W. Alton , Yildirim Melike F. , Zhang Alan F. , Reid Zuri , Stringfellow Erin J. , Bearnot Benjamin , Schackman Bruce R. , Humphreys Keith , Jalali Mohammad S.
Published: May 2023

Importance

Buprenorphine is an effective and cost-effective medication to treat opioid use disorder (OUD), but is not readily available to many people with OUD in the US. The current cost-effectiveness literature does not consider interventions that concurrently increase buprenorphine initiation, duration, and capacity.

Objective

To conduct a cost-effectiveness analysis and compare interventions associated with increased buprenorphine treatment initiation, duration, and capacity.

Design and Setting

This study modeled the effects of 5 interventions individually and in combination using SOURCE, a recent system dynamics model of prescription opioid and illicit opioid use, treatment, and remission, calibrated to US data from 1999 to 2020. The analysis was run during a 12-year time horizon from 2021 to 2032, with lifetime follow-up. A probabilistic sensitivity analysis on intervention effectiveness and costs was conducted. Analyses were performed from April 2021 through March 2023. Modeled participants included people with opioid misuse and OUD in the US.

Interventions

Interventions included emergency department buprenorphine initiation, contingency management, psychotherapy, telehealth, and expansion of hub-and-spoke treatment programs, individually and in combination.

Main Outcomes and Measures

Total national opioid overdose deaths, quality-adjusted life years (QALYs) gained, and costs from the societal and health care perspective.

Results

Projections showed that contingency management expansion would avert 3530 opioid overdose deaths over 12 years, more than any other single-intervention strategy. Interventions that increased buprenorphine treatment duration initially were associated with an increased number of opioid overdose deaths in the absence of expanded treatment capacity. With an incremental cost- effectiveness ratio of $19 381 per QALY gained (2021 USD), the strategy that expanded contingency management, hub-and-spoke training, emergency department initiation, and telehealth was the preferred strategy for any willingness-to-pay threshold from $20 000 to $200 000/QALY gained, as it was associated with increased treatment duration and capacity simultaneously.

Conclusion and Relevance

This modeling analysis simulated the effects of implementing several intervention strategies across the buprenorphine cascade of care and found that strategies that were concurrently associated with increased buprenorphine treatment initiation, duration, and capacity were cost-effective.
SAMHSA and FDA move toward ‘medication only’
Authors: Knopf Alison
Published: May 2023

Receiving buprenorphine should not be contingent upon receiving counseling as well, the federal government has said in a “Dear Colleague” letter issued May 9. The letter, from the Food and Drug Administration (FDA) and the Substance Abuse and Mental Health Services Administration (SAMHSA), states that “an often‐cited barrier to prescribing buprenorphine for the treatment of OUD [opioid use disorder] is the perception that patients must engage in counseling and other services in order to start or continue receiving the medication,” and goes on: “This letter serves to clarify the importance of counseling and other services as part of a comprehensive treatment plan, but to also reiterate that the provision of medication should not be made contingent upon participation in such services.”
Acute and Repeated Ozone Exposures Differentially Affect Circadian Clock Gene Expression in Mice
Authors: Sundar Isaac Kirubakaran , Duraisamy Santhosh Kumar , Choudhary Ishita , Saini Yogesh , Silveyra Patricia
Published: May 2023

Circadian rhythms have an established role in regulating physiological processes, such as inflammation, immunity, and metabolism. Ozone, a common environmental pollutant with strong oxidative potential, is implicated in lung inflammation/injury in asthmatics. However, whether O3 exposure affects the expression of circadian clock genes in the lungs is not known. In this study, changes in the expression of core clock genes are analyzed in the lungs of adult female and male mice exposed to filtered air (FA) or O3 using qRT‐PCR. The findings are confirmed using an existing RNA‐sequencing dataset from repeated FA‐ and O3‐exposed mouse lungs and validated by qRT‐PCR. Acute O3 exposure significantly alters the expression of clock genes in the lungs of females (Per1, Cry1, and Rora) and males (Per1). RNA‐seq data revealing sex‐based differences in clock gene expression in the airway of males (decreased Nr1d1/Rev‐erbα) and females (increased Skp1), parenchyma of females and males (decreased Nr1d1 and Fbxl3 and increased Bhlhe40 and Skp1), and alveolar macrophages of males (decreased Arntl/Bmal1, Per1, Per2, Prkab1, and Prkab2) and females (increased Cry2, Per1, Per2, Csnk1d, Csnk1e, Prkab2, and Fbxl3). These findings suggest that lung inflammation caused by O3 exposure affects clock genes which may regulate key signaling pathways.
Sequential‐Stimuli Induced Stepwise‐Response of Pyridylpyrenes
Authors: Zhang Yufeng , Zhang Shuai , Liang Chen , Shi Junqing , Ji Lei
Published: May 2023

Stimuli‐responsive materials, especially multi‐stimuli‐responsive materials, can sense external stimuli such as light, heat, and force, have shown great potential in drug delivery, data storage, encryption, energy‐harvesting, and artificial intelligence. Conventional multi‐stimuli‐responsive materials are sensitive to each independent stimulus, causing losses in the diversity and accuracy of the identification for practical application. Herein, a unique phenomenon of sequential‐stimuli induced stepwise‐response generated from elaborately designed single‐component organic materials is reported, which shows large bathochromic shifts up to 5800 cm−1 under sequential stimuli of force and light. In contrast to multi‐stimuli‐responsive materials, the response of these materials strictly relies on the sequence of stimuli, allowing logicality, rigidity, and accuracy to be integrated into one single‐component material. The molecular keypad lock is built based on these materials, pointing promising to a future for this logical response in significant practical applications. This breakthrough gives a new drive to classical stimuli‐responsiveness and provides a fundamental design strategy for new generations of high‐performance stimuli‐responsive materials.
Role of Potassium in Electrocatalytic Water Oxidation Investigated in a Volume‐Active Cobalt Material at Neutral pH
Authors: Liu Si , Farhoosh Shima , Beyer Paul , Mebs Stefan , Zaharieva Ivelina , Haumann Michael , Dau Holger
Published: May 2023

The oxygen evolution reaction (OER) is crucial in systems for sustainable production of hydrogen and other fuels. Catalytic OER materials often undergo potential‐induced redox transitions localized at metal sites. For volume‐active catalyst‐materials, these are necessarily coupled to charge‐compensating relocation of ions entering or leaving the material, which is insufficiently understood. The binding mode and mechanistic role of redox‐inert ions for a cobalt‐based oxyhydroxide material (CoCat) when operated at neutral pH in potassium‐phosphate (KPi) electrolyte are investigated by i) determination of K:Co and P:Co stoichiometries for various KPi‐concentrations and electrode potentials, ii) operando X‐ray spectroscopy at the potassium and cobalt K‐edges, and iii) novel time‐resolved X‐ray experiments facilitating comparison of K‐release and Co‐oxidation kinetics. Potassium likely binds non‐specifically within water layers interfacing Co‐oxyhydoxide fragments involving potassium–phosphate ion pairs. The potassium‐release kinetics are potential‐independent with a fast‐phase time‐constant of about 5 s and thus clearly slower than the potential‐induced Co oxidation of about 300 ms. It is concluded that the charge‐compensating ion flow is realized neither by potassium nor by phosphate ions, but by protons. The results reported here are likely relevant also for a broader class of volume‐active OER catalyst materials and for the amorphized near‐surface regions of microcrystalline materials.
Remodeling Serine Synthesis and Metabolism via Nanoparticles (NPs)‐Mediated CFL1 Silencing to Enhance the Sensitivity of Hepatocellular Carcinoma to Sorafenib
Authors: Li Senlin , Xu Lei , Wu Guo , Huang Ziqi , Huang Linzhuo , Zhang Fengqian , Wei Chunfang , Shen Qian , Li Rong , Zhang Lei , Xu Xiaoding
Published: May 2023

Tyrosine kinase inhibitors represented by sorafenib are the first‐line treatment for hepatocellular carcinoma (HCC), but the low response rate of HCC patient has become a clinical pain‐point. Emerging evidences have revealed that metabolic reprogramming plays an important role in regulating the sensitivity of tumor cells to various chemotherapeutics including sorafenib. However, the underlying mechanisms are very complex and are not fully elucidated. By comparing the transcriptome sequencing data of sorafenib‐sensitive and ‐insensitive HCC patients, it is revealed that cofilin 1 (CFL1) is highly expressed in the tumor tissues of sorafenib‐insensitive HCC patients and closely correlated with their poor prognosis. Mechanically, CFL1 can promote phosphoglycerate dehydrogenase transcription and enhance serine synthesis and metabolism to accelerate the production of antioxidants for scavenging the excessive reactive oxygen species induced by sorafenib, thereby impairing the sorafenib sensitivity of HCC. To translate this finding and consider the severe side effects of sorafenib, a reduction‐responsive nanoplatform for systemic co‐delivery of CFL1 siRNA (siCFL1) and sorafenib is further developed, and its high efficacy in inhibiting HCC tumor growth without apparent toxicity is demonstrated. These results indicate that nanoparticles‐mediated co‐delivery of siCFL1 and sorafenib can be a new strategy for the treatment of advanced HCC.
Locoregional treatment for colorectal liver metastases aiming for precision medicine
Authors: Maki Harufumi , Jain Anish J. , Haddad Antony , Lendoire Mateo , Chun Yun Shin , Vauthey Jean‐Nicolas
Published: May 2023

In patients with colorectal liver metastases (CLM), surgery is potentially curative. The use of novel surgical techniques and complementary percutaneous ablation allows for curative‐intent treatment even in marginally resectable cases. Resection is used as part of a multidisciplinary approach, which for nearly all patients will include perioperative chemotherapy. Small CLM can be treated with parenchymal‐sparing hepatectomy (PSH) and/or ablation. For small CLM, PSH results in better survival and higher rates of resectability of recurrent CLM than non‐PSH. For patients with extensive bilateral distribution of CLM, two‐stage hepatectomy or fast‐track two‐stage hepatectomy is effective. Our increasing knowledge of genetic alterations allows us to use them as prognostic factors alongside traditional risk factors (e.g. tumor diameter and tumor number) to select patients with CLM for resection and guide surveillance after resection. Alteration in RAS family genes (hereafter referred to as “RAS alteration”) is an important negative prognostic factor, as are alterations in the TP53, SMAD4, FBXW7, and BRAF genes. However, APC alteration appears to improve prognosis. RAS alteration, increased number and diameter of CLM, and primary lymph node metastasis are well‐known risk factors for recurrence after CLM resection. In patients free of recurrence 2 y after CLM resection, only RAS alteration is associated with recurrence. Thus, surveillance intensity can be stratified by RAS alteration status after 2 y. Novel diagnostic instruments and tools, such as circulating tumor DNA, may lead to further evolution of patient selection, prognostication, and treatment algorithms for CLM.
Copper/Photoredox dual Catalyzed Syntheses of Allenenitriles via 1,5‐HAT
Authors: Li Yuan‐Bo , Bi Yu‐Xiang , Ke Wen‐Chang , Wang Cheng‐Yu , Hu Duo‐Duo , Li Yan , Wang Xi‐Sheng
Published: May 2023

The first example of merging photoredox catalysis and copper catalysis for 1,4‐difunctionalization of 1,3‐enynes via 1,5‐HAT (hydrogen atom transfer) has been developed. The synthetic strategy exploits a radical translocation from an oxygen‐centered to a carbon‐centered radical with a subsequent radical addition to the 1,3‐enynes, affording tetrasubstituted allenenitriles in up to 90% yield. This strategy has mild reaction conditions, broad substrate scope and excellent functional group tolerance.
Perilipin 5 regulates hepatic stellate cell activation and high‐fat diet‐induced non‐alcoholic fatty liver disease
Authors: Yin Xuecui , Dong Lin , Wang Xiaohan , Qin Zhenzhen , Ma Yuying , Ke Xiaofei , Li Ya , Wang Qingde , Mi Yang , Lyu Quanjun , Xu Xia , Zheng Pengyuan , Tang Youcai
Published: May 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases globally. Hepatic stellate cells (HSCs) are the major effector cells of liver fibrosis. HSCs contain abundant lipid droplets (LDs) in their cytoplasm during quiescence. Perilipin 5 (PLIN 5) is a LD surface‐associated protein that plays a crucial role in lipid homeostasis. However, little is known about the role of PLIN 5 in HSC activation.

Methods

PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection. At the same time, PLIN 5 gene knockout mice were constructed and fed with a high‐fat diet (HFD) for 20 weeks to study the role of PLIN 5 in NAFLD. The corresponding reagent kits were used to measure TG, GSH, Caspase 3 activity, ATP level, and mitochondrial DNA copy number. Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC‐MS/MS. AMPK, mitochondrial function, cell proliferation, and apoptosis‐related genes and proteins were detected by western blotting and qPCR.

Results

Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria, inhibition of cell proliferation, and a significant increase in cell apoptosis through AMPK activation. In addition, compared with the HFD‐fed C57BL/6J mice, PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition, decreased LD abundance and size, and reduced liver fibrosis.

Conclusion

These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.
Interlaboratory comparisons of cyanotoxin analysis by ELISA and LC–MS/MS
Authors: Prescott Matthew D. , Jia Ai , Guo Yingbo C. , Di Giovanni George D. , Li Wei L. , Garcia Eduardo A. , Vanderford Brett J. , Eaton Andrew D.
Published: May 2023

Two commonly used methods for cyanotoxin analysis are enzyme‐linked immunosorbent assay (ELISA) and liquid chromatography/tandem mass spectrometry (LC–MS/MS). Two rounds of interlaboratory comparisons of ELISA and LC–MS/MS analyses were conducted with 12 participating laboratories to evaluate method performances in various matrices, including cyanobacterial bloom and drinking water samples. Fifteen cyanotoxins, including 12 microcystin variants, nodularin, anatoxin‐a, and cylindrospermopsin were evaluated. The impact of sample matrices, preservatives, and quenching reagents was assessed, and no substantial effects were observed. Overall, comparable results were obtained among laboratories performing ELISA and LC–MS/MS analyses, respectively. ELISA results for fortified samples matched more closely with those from LC–MS/MS when microcystin cross‐reactivities were considered, providing data 26% closer to theoretical values on average. This study demonstrates that understanding the effect of cross‐reactivities when comparing ELISA and LC–MS/MS results and considering potential variabilities in commercial standards is important when interpreting data from these two methods.
The Use of Reductive Agents for Developing Capacity Balanced Aqueous Sodium‐Ion Batteries
Authors: Petrulevičienė Milda , Traškina Nadežda , Pilipavičius Jurgis , Juodkazytė Jurga , Vilčiauskas Linas
Published: May 2023

Aqueous sodium‐ion batteries (Na‐ion batteries) represent an attractive low cost stationary energy storage technology. However, limited electrochemical stability of water and issues related to complex aqueous chemistry, component corrosion, and materials dissolution limit their lifetime. Oxygen reduction reaction is considered to be the main parasitic process in aqueous Na‐ion batteries leading to self‐discharge, materials degradation and Na‐ion inventory loss. Herein, we present a comprehensive study on novel electrolyte design which allows to mitigate the main parasitic reactions and prepare capacity balanced (N/P=1) aqueous battery cells. For this purpose, aqueous symmetric Na2VTi(PO4)3|Na2VTi(PO4)3 system is used as a model to demonstrate that the introduction of a small concentration of strongly reducing agent such as hydrazine into purely aqueous or hybrid (water and dimethyl sulphoxide) electrolyte could chemically reduce the dissolved oxygen and significantly improve the capacity retention of N/P=1 cells during cycling. The low concentrations and self‐consuming nature of hydrazine in a closed cell do not pose any health or chemical risks and presents a viable strategy for practical design. We believe, these results to be applicable not only to aqueous Na‐ion batteries but also other aqueous or hybrid battery chemistries where such parasitic processes play a significant role.
Engineering single‐domain antibodies targeting Gasdermin E activation by the chemotherapeutic agent cis‐diaminodichloroplatinum
Authors: Ma Jinyi , Xu Jintao , Gao Qiuyun , Sun Yanan , Wang Yu , Liu Zhe , Ma Zhenyi
Published: May 2023

As mediators of pyroptosis, gasdermins (GSDMs) are closely associated with systemic cytotoxicity or so‐called side effects and are also involved in the inflammatory response during chemotherapy. Using in situ proximity ligation assay followed by sequencing (isPLA‐seq), which we recently developed, we screened a single‐domain antibody (sdAb) library and identified several sdAbs against Gasdermin E (GSDME) that specifically recognize the N‐terminal domain (1‐270 aa) of GSDME (GSDME‐NT). One of them mitigated the release of inflammatory damage‐associated molecular patterns (DAMPs) and cytokines, including high mobility group protein b1 (Hmgb1) and interleukin‐1β (Il‐1β), in isolated mouse alveolar epithelial cells (AECs) upon chemotherapeutic agent cis‐diaminodichloroplatinum (CDDP) treatment. Further investigation showed that this anti‐GSDME sdAb also alleviated CDDP‐induced pyroptotic cell death and lung tissue injury and decreased systemic Hmgb1 release in C57/BL6 mice, due to GSDME inactivation. Collectively, our data define an inhibitory role of the specific sdAb against GSDME, providing a potential strategy for systemically alleviating chemotherapeutic toxicities in vivo.
Design, Synthesis and Cytotoxicity of New Coumarin‐1,2,3‐triazole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies
Authors: Premsagar Miriyala Victor , Raj Thommandru Prakash , Kashanna Jajula , Govinda Varadhi , Ravi Guguloth , Kishore Ravada
Published: May 2023

A library of new coumarin‐1,2,3‐triazole hybrids 7a–l were synthesized from 4‐(diethylamino)‐2‐hydroxybenzaldehyde precursor through a series of reactions including Vilsmeier‐Haack reaction and condensation reaction to achieve key intermediate oxime and further performed click reaction by using different aromatic azides. We screened all molecules in silico against crystal structure of Serine/threonine‐protein kinase 24 (MST3), based on these results all molecules were screened for their cytotoxicity against human breast cancer MCF‐7 and lung cancer A‐549 cell lines. Compound 7 b (p‐bromo) showed best activity against both cell lines MCF‐7 and A‐549 with IC50 value of 29.32 and 21.03 μM, respectively, in comparison to Doxorubicin corresponding IC50 value of 28.76 and 20.82 μM. Another compound 7 f (o‐methoxy) also indicated good activity against both cell lines with IC50 value of 29.26 and 22.41 μM. The toxicity of all compounds tested against normal HEK‐293 cell lines have not shown any adverse effects.
Imaging findings of superficial angiomyxoma in the eye socket
Authors: Chen Guiwu , Liu Wenqin , Cao Yongjie , Guo Xiaodong , Xie Yuhuan
Published: May 2023

Key Clinical Message

A 23‐year‐old male with a tumor in the eye socket was characterized by multimodal images, including ultrasonography, computed tomography, and magnetic resonance imaging. After admission, surgical resection of the tumor was performed and superficial angiomyxoma was confirmed. Two years later, this tumor recurred in the same location.

Superficial angiomyxoma (SAM) is a rare benign neoplasm composed mostly of myxoid material that can affect many parts of the body in middle‐aged patients. Only a few case reports have involved imaging, which is extremely insufficient. Here, we present a case of SAM in the eye socket evaluated by imaging, including ultrasonography, computed tomography, and magnetic resonance imaging. The patient underwent surgical resection, and the diagnosis of SAM was confirmed. During the postoperative follow‐up, the tumor recurred in the same location without metastasis 2 years later.
Tuning the photophysical and chiroptical properties of [4]helicene‐diketopyrrolopyrroles
Authors: Mastropasqua Talamo Maurizio , Cauchy Thomas , Zinna Francesco , Pop Flavia , Avarvari Narcis
Published: May 2023

Synthesis and functionalization of diketopyrrolo[3,4‐c]pyrrole (DPP) derivatives containing chiral groups able to induce a strong chiral perturbation of the DPP core are still a challenging task. We report in this work the straightforward preparation of four bis([4]helicene)‐DPP and bis([4]thiahelicene)‐DPP dyes upon the condensation of 2‐CN‐[4](thia)helicene precursors, followed by their N‐alkylation by nucleophilic substitution (compounds 9–11) or by a Mitsunobu‐type strategy (compound 12). Compound 12, which contains sec‐phenylethyl groups attached to the nitrogen atoms, has been obtained as (R,R) and (S,S) enantiomers. The four DPP‐helicenes are luminescent in solution, while the N‐benzyl (10) and N‐sec‐phenethyl (12) are emissive in the solid state as well. The chiroptical properties of compound 12 in solution and in the solid state indicate a strong chiral perturbation provided by the α‐stereogenic centres, in spite of the stereodynamic nature of the [4]helicene flanking units.
Speciation and Photoluminescent Properties of a 2,6‐Bis(pyrrol‐2‐yl)pyridine in Three Protonation States
Authors: Leary Dylan C. , Martinez Jordan C. , Gowda Anitha S. , Akhmedov Novruz G. , Petersen Jeffrey L. , Milsmann Carsten
Published: May 2023

2,6‐Bis(pyrrol‐2‐yl)pyridines are important building blocks for supramolecular assemblies and photoluminescent main group and transition metal compounds. Sterically encumbered 2,6‐bis(5‐(2,4,6‐trimethylphenyl)‐3‐phenyl‐1H‐pyrrol‐2‐yl)pyridine, H2MesPDPPh, can adopt monomeric and dimeric structures in the solid state and in solution, controlled by competing inter‐ and intramolecular hydrogen bonds. Deprotonation in the presence of lithium cations provides Li2MesPDPPh, which can be isolated in monomeric and dimeric forms depending on solvent polarity. Protonation of H2MesPDPPh disrupts intramolecular hydrogen bonding and provides the monomeric pyridinium salt [H3MesPDPPh]Cl. Independent of solvent polarity, all three derivatives exhibit intense fluorescence in solution. The absorption and emission spectra are highly sensitive to the level of protonation, which can be rationalized by the effects of (de)protonation on the HOMO and LUMO of the tricyclic π‐system.
Transformation and Mutagenesis of Chlamydia trachomatis and C. muridarum Utilizing pKW Vector
Authors: Wolf Katerina
Published: May 2023

A gene deletion by allelic exchange via homologous recombination from a bacterial genome represents a valuable genetic tool for studying a role(s) of determinants involved in various aspects of pathogenesis. Due to chlamydial obligate intracellular lifestyle and comparatively low transformation rate, the mutagenesis of Chlamydia utilizes types of suicide vectors that have to be maintained and propagated by the bacteria throughout several rounds of their intracellular developmental cycle. These deletion constructs must be lost by chlamydiae once null mutant formation is achieved. pKW is a small, 5.45 bp, pUC19‐derived vector, which has been recently successfully employed for the generation of deletion mutants in C. trachomatis, serovariant D, and C. muridarum. This vector contains both, E. coli as well as chlamydial species‐specific plasmid origins of replication, allowing for its propagation by both bacterial genera under a selective pressure. However, once the selective antibiotic is removed from culture, chlamydiae rapidly lose pKW, and the subsequent reintroduction of the selective antibiotic back to chlamydiae‐infected cells results efficiently in the selection of generated deletion mutants. Protocols provided here describe in detail the preparation of pKW deletion constructs for C. trachomatis and C. muridarum applicable for chlamydial transformation and the production of null mutant in non‐essential genes. Protocols provided here, are describing in detail methods for assembly of the pKW shuttle vector and generation of deletion mutants in C. trachomatis and C. muridarum. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Assembly of pKW shuttle vector

Basic Protocol 2: Generation of a deletion mutant in C. trachomatis, serovars D and L2 and, Chlamydia muridarum

Support Protocol: Transformation of C. trachomatis, serovars B
Z number improved reference ideal method‐based decision‐making process for enforcing cooperation during data dissemination in mobile ad hoc networks
Authors: Mylsamy Rajkumar , Jayaprakash Karthika
Published: May 2023

In mobile ad hoc networks (MANETs), cooperative communication and resource constraint are the two important core characteristics essential to guarantee trusted data dissemination. The cooperative communication between mobile nodes depends on the trust rendered by them towards the process of reliable data routing. However, stringent resource constraints of mobile nodes such as energy, memory, communications, and computations result in the introduction of selfish and malicious node that completely degrades the network performance in different dimensions. In this paper, Z number improved reference ideal method (RIM)‐based decision‐making process (NIRIMDMP) is proposed with the merits of maximizing deviation method (MDM) and best–worst method (BWM) to ensure reliable data routing by modeling the cooperation degree in terms of Z number. This NIRIMDMP adopted Z number to represent the information reliability and handle the problem of inherent uncertainty during the process of evaluating each mobile node in the routing process. In specific, MDM and BWM are included into the proposed NIRIMDMP to determine comprehensive attribute weights based on the calculated objective and subjective weights that could be possible derived in routing. It extended the merits of classical RIM using Z numbers to confirm reliable ranking of mobile nodes, even when the optimal solution exists amid extreme values taken into consideration for assessing the mobile nodes during decision making. Simulation investigations of the proposed NIRIMDMP confirmed improved throughput and network lifetime with reduced control overhead, energy consumptions, and delay independent of the amount of malicious and non‐cooperative nodes.
Storm‐flood‐dominated delta succession in the Pleistocene Taiwan Strait
Authors: Vaucher Romain , Dillinger Antoine , Hsieh Amy I. , Chi Wen‐Rong , Löwemark Ludvig , Dashtgard Shahin E.
Published: May 2023

Storm‐flood‐dominated deltas are sedimentary systems in which a complex interplay of hydrodynamic processes occurs during storms (e.g. tropical cyclones) due to the coeval action of continental and oceanic processes. This paper reports on a superbly exposed, 135.5 m thick stratigraphic succession of the Pleistocene Cholan Formation exposed along the Da'an River, Taiwan. The sedimentary succession comprises alternating mudstone and sandstone, is mostly fine‐grained, and exhibits multiple event beds that record deposition during tropical cyclones and post‐depositional deformation features produced during earthquakes. Detailed facies analyses reveal that deposition towards the base of the succession occurred in the palaeo‐Taiwan Strait in storm‐flood‐dominated prodelta and delta‐front environments passing upwards into delta‐plain environments. Tropical cyclone beds are encountered throughout the subaqueous storm‐flood delta successions, and are identified by (i) trough cross‐stratified sandstone bedsets with erosive bases that contain both mud clasts and mudstone beds, (ii) sandstone with aggrading wave ripples and (iii) hummocky cross‐stratified sandstone with rare gutter casts filled with coal fragments and shell remains. Tropical cyclone deposits are either top‐down burrowed or capped by massive or laminated mudstone. Seismites are rare and are mainly recognised through soft‐sediment deformation of beds; they do not show evidence of slope failure. Compared to storm‐flood delta successions described elsewhere, the Cholan Formation shows significantly fewer oscillatory‐generated sedimentary structures and gutter casts. This difference is attributed to the Cholan Formation being deposited in and along the margin of a strait characterised by strong shore‐parallel currents and relatively small storm waves due to its position between Taiwan and mainland China. This study refines depositional process interpretations of the Cholan Formation, provides criteria for recognising storm‐flood delta deposits in tectonically active straits with multiple sediment sources fed by steep drainages and short river catchments, and provides additional criteria for recognising tropical cyclone deposits in shallow‐marine settings.
Adverse events seen with fillers
Authors: Lateef Almeera , Barker Catherine , Snyder Alan , Vaishnav Yash , Schlesinger Todd
Published: May 2023

Dermal fillers are often utilized to enhance facial features as well as correct signs of aging on the face. Common side effects seen with dermal fillers are injection site erythema, edema, and secondary infection. Uncommon yet severe effects of filler injection result from vascular occlusion, causing skin necrosis, blindness, or even stroke. Vision loss typically occurs immediately after injection. Partial vision loss is associated with better prognosis. In case of visual compromise, an ocular massage and reduction of ocular pressure should be initiated immediately. The instruments used as well as the pressure and volume of the injection can contribute to unwanted complications. Anti‐thrombolytics, including hyaluronidase for hyaluronic acid injection, may offer some benefit in the case of vascular occlusion. Aesthetic providers must have thorough knowledge of facial anatomy and proper injection technique to mitigate the risk of these dreaded adverse events.
Drought, fire, and rainforest endemics: A case study of two threatened frogs impacted by Australia's “Black Summer”
Authors: Heard Geoffrey W. , Bolitho Liam J. , Newell David , Hines Harry B. , Norman Patrick , Willacy Rosalie J. , Scheele Ben C.
Published: May 2023

Deepening droughts and unprecedented wildfires are at the leading edge of climate change. Such events pose an emerging threat to species maladapted to these perturbations, with the potential for steeper declines than may be inferred from the gradual erosion of their climatic niche. This study focused on two species of amphibians—Philoria kundagungan and Philoria richmondensis (Limnodynastidae)—from the Gondwanan rainforests of eastern Australia that were extensively affected by the “Black Summer” megafires of 2019/2020 and the severe drought associated with them. We sought to assess the impact of these perturbations by quantifying the extent of habitat affected by fire, assessing patterns of occurrence and abundance of calling males post‐fire, and comparing post‐fire occurrence and abundance with that observed pre‐fire. Some 30% of potentially suitable habitat for P. kundagungan was fire affected, and 12% for P. richmondensis. Field surveys revealed persistence in some burnt rainforest; however, both species were detected at a higher proportion of unburnt sites. There was a clear negative effect of fire on the probability of site occupancy, abundance and the probability of persistence for P. kundagungan. For P. richmondensis, effects of fire were less evident due to the limited penetration of fire into core habitat; however, occupancy rates and abundance of calling males were depressed during the severe drought that prevailed just prior to the fires, with the reappearance of calling males linked to the degree of rehydration of breeding habitat post‐fire. Our results highlight the possibility that severe negative impacts of climate change for montane rainforest endemics may be felt much sooner than commonly anticipated under a scenario of gradual (decadal‐scale) changes in mean climatic conditions. Instead, the increased rate of severe stochastic events places these narrow range species at a heightened risk of extinction in the near‐term.
Plastic maternal effects of social density on reproduction and fitness in the least killifish, Heterandria formosa
Authors: Levell Samantha T. , Bedgood Samuel A. , Travis Joseph
Published: May 2023

Environmental parental effects, also known as transgenerational plasticity, are widespread in plants and animals. Less well known is whether those effects contribute to maternal fitness in the same manner in different populations. We carried out a multigenerational laboratory experiment with females drawn from two populations of the least killifish, Heterandria formosa, to assess transgenerational plasticity in reproductive traits in response to differences in social density and its effects on maternal fitness. In the first and second generations, increased density decreased reproductive rate and increased offspring size in females from both populations. There were complicated patterns of transgenerational plasticity on maternal fitness that differed between females from different populations. Females from a population with historically low densities whose mothers experienced lower density had higher fitness than females whose mothers experienced higher density, regardless of their own density. The opposite pattern emerged in females from the population with historically high densities: Females whose mothers experienced higher density had higher fitness than females whose mothers experienced lower density. This transgenerational plasticity is not anticipatory but might be considered adaptive in both populations if providing those “silver spoons” enhances offspring fitness in all environments.
Rift Valley fever virus outbreak in Mauritania yet again in 2022: No room for complacency
Authors: Tabassum Shehroze , Naeem Farhan , Azhar Masood , Naeem Aroma , Oduoye Malik O. , Dave Tirth
Published: May 2023

Rift Valley fever is an important yet ignored viral hemorrhagic fever claiming many lives of African and Arabian countries over the past decade. Unfortunately, a recent outbreak of Rift Valley fever is currently ravaging in Mauritania. Death toll is rising continuously with 23 deaths reported in the month of October, 2022. Our article aims to shed light on the ongoing Rift Valley fever outbreak and recommendations to eradicate this potential threat to public health. Online databases including PubMed, the Lancet, and Science Direct as well as conferences, news, and press releases were used to for data collection. All the available medical literature related to Rift Valley fever in Mauritania were taken into consideration while writing the manuscript. As of October 17, 2022, 47 cases have been documented out of which 23 are dead. Case fatality rate has been reached to 49% which has given a wakeup call to the authorities. Efforts are being made by the concerned authorities and World Health Organization to halt the progression of this outbreak. Further investigations are required to completely eradicate the recurrent outbreaks in Mauritania especially in the area of vaccine development. Active involvement of public with the government authorities is of extreme significance in combating this disease.
A pilot study of offering a positive disciplining module for public school teachers in Hyderabad, Pakistan: A quasi‐experimental study
Authors: Mughal Farida Bibi , Karmaliani Rozina , Asad Nargis , Bhamani Shireen Shehzad
Published: May 2023

A pilot quasi‐experimental study was conducted in which participants in the intervention group (n = 31) received positive learning environment through Positive Disciplining (PLEPD) module, while those in the control group (n = 29) received routine training. Teachers' knowledge and attitude regarding corporal punishment (CP) and Beck Depression Inventory‐II (BDI‐II) were measured before (T0), immediately after (T1) and 3 months after the intervention (T2). Descriptive analysis and analysis of variance (ANOVA) were used to describe participants' characteristics and mean scores for knowledge and attitude among teachers. A total of 60 teachers completed the 16 hours training module. The overall response rate was >90%. Most participants recommended increasing the overall duration of the programme by reducing 4 to 2 hours per day, thus, increasing the period from 4 to 8 days of training. There were no differences between control and intervention groups at baseline regarding participant characteristics (p= > .05). The difference in depression (F = .0863, p = .357) and knowledge and attitude (F = 1.589, p = .213) scores among groups were not statistically significant. However, the mean score for knowledge and attitude followed a positive trend, increasing depression mean scores at T1 and T2. A positive disciplining programme is a feasible school intervention for public schools and may effectively reduce depression to ensure overall well‐being.
Target selection and clinical chimeric antigen receptor T cell activity against solid tumors
Authors: von Hofe Eric , Yang Yanping , Jin Moonsoo M.
Published: May 2023

Chimeric antigen receptor (CAR) T cell therapy is a relatively new form of targeted therapy that has demonstrated impressive success in treating hematological malignancies. It has been challenging to translate this success to solid tumors. Reasons for this include barriers to delivery, tumor heterogeneity, cancer cells' ability to evade the immune system as well as identifying the optimal target. Most CAR T clinical trials have targeted well‐characterized cancer targets with significant preclinical and in some cases clinical validation. Published results from some of these trials show signs of anti‐cancer activity that warrant encouragement, but also caution, given instances of unacceptable toxicity. The narrow therapeutic window is complicated by the ability of CAR T cells to expand in patients regardless of dose. Here, we review those trials showing encouraging results in the context of target selection. It is clear that more specific tumor targeting is required, either by affinity tuning to avoid low‐level target expression in healthy cells, logic gating, or the identification of new targets that are more cancer specific.
Natural 3D Extra Cellular Matrix mimicking stem cells seeded decellularized scaffolds as a platform for tendon regeneration
Authors: Niveditha K. , John Annie , Joseph Josna , Mini S. , Vineeth C. A. , Swapna T. S. , Abraham Annie
Published: May 2023

Achilles tendon, which connects the calf muscles to heel, is the strongest tendon in the body. Despite its strength, it is more prone to injury due to its limited blood supply. Tendon‐related injuries are more common in sportspersons, people with labor‐intensive work and the aged community. The currently available treatment mode is surgery which is expensive with chances of re‐injury. Present study made an attempt to fabricate a tissue‐engineered tendon product using decellularized tendon (DT) seeded with stem cells and bioactive components of Tinospora cordifolia extract (TCE). The bare DT tissue scaffold/substitute may also serve as a drug delivery platform for growth factors and cells with a new approach to promote tissue regeneration in clinical applications. DT construct showed good regenerative potential and easily promoted new tissue formation. Decellularization of the tendon was carried out by chemical method using tri (n‐butyl) phosphate (TnBP). DT was physicochemically characterized by contact angle measurement, thermal gravimetric analysis (TGA), and mechanical testing. Rabbit adipose derived mesenchymal stem cells (RADMSCs) were isolated and phenotypically characterized by flow cytometry analysis, tri lineage differentiation, and so forth. Further, stem cell seeded DT scaffolds were prepared and found to be non‐toxic by cytotoxicity, cell adhesion by scanning electron microscope (SEM) analysis, cell viability by live dead assays, and so forth. The findings of this study yield valid proof for the employability of cell‐seeded DT construct as a natural scaffold in repairing injured tendons—the toughest chords of the skeleton. This is a cost effective method for the replacement of injured/damaged tendons for athletes, people in labor‐intensive occupations, the elderly population, and so forth—a boon towards the repair of the tendon in damage/injury.
School counselors’ experiences strengthening classroom instruction through professional development
Authors: Dack Hilary , Merlin‐Knoblich Clare
Published: May 2023

The field of school counseling has evolved to feature varied means of supporting students, including individual counseling, group counseling, and classroom instruction. However, classroom instruction is typically overlooked in school counselor training programs, and school counselors often lack the skills needed to design effective lessons. This longitudinal study explored the experiences of 21 school counselors in a year‐long, post‐master's professional development program focused on improving classroom instruction. Data were drawn from interviews, curricular artifacts, and reflective journals and analyzed using interpretive qualitative methodology. This study's contributions lie in findings that illustrate school counselors’ nuanced perceptions of the utility of the Understanding by Design instructional approach as a framework for implementing ASCA Student Standards; the utility of learning science as a framework for designing classroom instruction that leads to long‐term learning; and supports or challenges to implementing classroom instruction in individual contexts.
Post‐hatching developmental changes in the adrenal gland of the Japanese quail (Coturnix coturnix japonica): Histological, immunohistochemical, and electron microscopic studies
Authors: Abdel‐maksoud Fatma M. , Fadl Saher , Abou‐Elmagd Ahmed , Saleh Abdelmohaimen M.M.
Published: May 2023

The adrenal glands are paired abdominal endocrine organs vital to the bird's health. The present research aimed to provide a comprehensive examination of the histological, ultrastructural, and immunohistochemical investigations of the adrenal gland in Japanese quail during the post hatching period. The current study was performed on 21 healthy Japanese quail chicks at different post hatching periods. Our results showed the adrenal gland is surrounded by a connective tissue capsule, which consists of dense collagen fibers containing large blood vessels, chromaffin cells, autonomic ganglia, fibroblasts, and migrating Schwann cells. The zonation of the adrenal gland is composed of a subcapsular layer, a peripheral zone, and a central zone, which gets more pronounced with age. At the ultrastructural level, the interrenal cells take the steroid‐secreting cells characters; they have varying amounts of lipid droplets and abundant mitochondria. Adrenal medullary chromaffin cells showed positive immunoreactivity to the NSE. With increasing age, the chromaffin tissue's Sox10 immunoreactivity increased. β‐catenin is expressed within the plasmalemma and the cytoplasm of the interrenal and chromaffin cells and its reactivity increased with age, especially in the chromaffin cells. Our results indicate the adrenal gland undergoes significant morphological changes during the postnatal life. Overall, the postnatal period is an important time for the development and maturation of the adrenal glands.