bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate Change and Aging Health in Developing Countries
Authors: Sarkar Sabrina Maria , Dhar Bablu Kumar , Fahlevi Mochammad , Ahmed Selim , Hossain Md. Jamal , Rahman Mohammad Meshbahur , Gazi Md. Abu Issa , Rajamani Ranjithkumar
Published: August 2023

The climate of the Earth has changed throughout history. Climate change negatively impacts human rights in a wide range of ways. The study aims to find out the impact of climate change on aging health in developing countries. The study found that public health will be devastated if climate change continues unabated. Countries that are least responsible for global warming are most susceptible to the effects of higher temperatures, such as death and disease. In low‐ and middle‐income countries, disasters are more likely to happen to people aged 60 and over. Although climate change affects all of us, older people are especially at risk from it, as evidenced by a growing body of research. The study also offers countermeasures and suggestions to develop aging health in developing countries affected by climate change.
Recent Progress of Droplet Microfluidic Emulsification Based Synthesis of Functional Microparticles
Authors: Long Fei , Guo Yanhong , Zhang Zhiyu , Wang Jing , Ren Yong , Cheng Yuchuan , Xu Gaojie
Published: August 2023

The remarkable control function over the functional material formation process enabled by droplet microfluidic emulsification approaches can lead to the efficient and one‐step encapsulation of active substances in microparticles, with the microparticle characteristics well regulated. In comparison to the conventional fabrication methods, droplet microfluidic technology can not only construct microparticles with various shapes, but also provide excellent templates, which enrich and expand the application fields of microparticles. For instance, intersection with disciplines in pharmacy, life sciences, and others, modifying the structure of microspheres and appending functional materials can be completed in the preparation of microparticles. The as‐prepared polymer particles have great potential in a wide range of applications for chemical analysis, heavy metal adsorption, and detection. This review systematically introduces the devices and basic principles of particle preparation using droplet microfluidic technology and discusses the research of functional microparticle formation with high monodispersity, involving a plethora of types including spherical, nonspherical, and Janus type, as well as core–shell, hole–shell, and controllable multicompartment particles. Moreover, this review paper also exhibits a critical analysis of the current status and existing challenges, and outlook of the future development in the emerging fields has been discussed.
Increased membrane Ca2+ permeability drives astrocytic Ca2+ dynamics during neuronal stimulation at excitatory synapses
Authors: Hjukse Jarand B. , Puebla Mario F. D. L. , Vindedal Gry Fluge , Sprengel Rolf , Jensen Vidar , Nagelhus Erlend A. , Tang Wannan
Published: August 2023

Astrocytes are intricately involved in the activity of neural circuits; however, their basic physiology of interacting with nearby neurons is not well established. Using two‐photon imaging of neurons and astrocytes during higher frequency stimulation of hippocampal CA3‐CA1 Schaffer collateral (Scc) excitatory synapses, we could show that increasing levels of released glutamate accelerated local astrocytic Ca2+ elevation. However, blockage of glutamate transporters did not abolish this astrocytic Ca2+ response, suggesting that astrocytic Ca2+ elevation is indirectly associated with an uptake of extracellular glutamate. However, during the astrocytic glutamate uptake, the Na+/Ca2+ exchanger (NCX) reverse mode was activated, and mediated extracellular Ca2+ entry, thereby triggering the internal release of Ca2+. In addition, extracellular Ca2+ entry via membrane P2X receptors further facilitated astrocytic Ca2+ elevation via ATP binding. These findings suggest a novel mechanism of activity induced Ca2+ permeability increases of astrocytic membranes, which drives astrocytic responses during neuronal stimulation of CA3‐CA1 Scc excitatory synapses.
The relevance of the hematopoietic niche for therapy resistance in acute myeloid leukemia
Authors: Allert Catana , Müller‐Tidow Carsten , Blank Maximilian Felix
Published: August 2023

The expansion of acute myeloid leukemia (AML) blasts not only suppresses normal hematopoiesis, but also alters the microenvironment. The interplay of different components of the bone marrow gives rise to altered metabolic states and activates signaling pathways which lead to resistance and impede effective therapy. Therefore, the underlying processes and mechanisms represent attractive therapeutic leverage points for overcoming therapy resistance in AML. Here, we briefly discuss resistance mechanisms based on cell interactions and secreted soluble factors in the hematopoietic niche and provide an overview of niche‐related therapeutic targets currently undergoing preclinical and clinical investigation which may help improve the outcome in AML therapy.
Association of prenatal thoracic ultrasound abnormalities with copy number variants at a single Chinese tertiary center
Authors: Huang Qiong , Zhang Yongling , Jing Xiangyi , Li Fucheng , Qin Jiachun , Li Fatao , Li Dongzhi , Li Ru , Liao Can
Published: August 2023

Objective

To systematically evaluate the association of prenatal thoracic ultrasound abnormalities with copy number variants (CNVs).

Methods

Chromosomal microarray (CMA) data and clinical characteristics from fetuses with thoracic ultrasound abnormalities were retrieved and analyzed.

Results

Thoracic ultrasound findings were mainly isolated except for fetal pleural effusion (FPE) and pulmonary hypoplasia. The diagnostic yield of CMA for thoracic anomaly was 9.66%, and FPE (17/68, 25%), pulmonary hypoplasia (1/8, 12.5%), and congenital diaphragmatic hernia (CDH) (6/79, 7.59%) indicated relatively high pathogenic/likely pathogenic (P/LP) CNV findings. The detection rate for P/LP CNVs was obviously increased in non‐isolated thoracic anomalies (27.91% vs. 1.96%, P < 0.0001), non‐isolated FPE (37.78% vs. 0%, P = 0.0007) and non‐isolated congenital pulmonary airway malformation (CPAM) (27.27% vs. 0%, P < 0.0001), and significantly different among thoracic anomalies. Additionally, the rate of termination of pregnancy in cases with non‐isolated thoracic anomalies (58.49% vs. 12.34%, P < 0.0001) and P/LP CNVs (85.71% vs. 24.15%, P < 0.0001) was obviously increased.

Conclusion

The present study expanded phenotype spectrums for particular recurrent CNVs. FPE, CDH, and pulmonary hypoplasia indicated relatively high P/LP CNV findings among common thoracic ultrasound abnormalities, CPAM associated with other ultrasound abnormalities increased the incidence of diagnostic CNVs, while bronchopulmonary sequestration might not be associated with positive CNVs. The present data recommended CMA application for cases with prenatal thoracic ultrasound abnormalities, especially non‐isolated FPE, non‐isolated CPAM, CDH, and pulmonary hypoplasia.
Do markers of daily affect mediate associations between interpretation bias and depressive symptoms? A longitudinal study of early adolescents
Authors: Grocott Bronwen , Battaglini Ashley M. , Jopling Ellen , Tracy Alison , Rnic Katerina , Sanchez‐Lopez Alvaro , LeMoult Joelle
Published: August 2023

Introduction

Early adolescence represents a time of heightened vulnerability for depression. Negative interpretation biases have been associated with increases in depressive symptoms during this developmental period; however, the mechanisms underlying the association between interpretation biases and depression remain poorly understood. Cognitive theories posit that interpretation biases give rise to depression by modulating daily affect, particularly in the context of stress. However, this has not yet been directly examined. The present study tested affect intensity and instability as mechanisms linking negative interpretation biases with change in adolescent depressive symptoms.

Methods

Ninety‐four adolescents (aged 11–13 years; 51% boys) from Vancouver, Canada, were recruited for this longitudinal study. At baseline (Time 1), participants self‐reported depressive symptoms and completed the Scrambled Sentences Task to assess negative interpretation biases. Next, participants completed daily diaries to assess positive affect (PA) and negative affect (NA) during a naturalistic stressor—the first 2 weeks of high school (Time 2). Finally, participants self‐reported depressive symptoms 3 months later (Time 3). Path models were conducted to test whether PA and NA intensity and instability mediated prospective associations between negative interpretation biases and depressive symptom changes.

Results

Although NA intensity, NA instability, and PA instability predicted increases in depressive symptoms, only NA intensity mediated associations between interpretation biases and symptom changes. Neither PA intensity nor instability mediated these associations.

Conclusions

Elevated daily NA represents a specific mechanism through which stronger negative interpretation biases predict increases in depressive symptoms in adolescence.
Chitosan thread in the healing of the cecal wall of rabbits (Oryctolagus cuniculus) submitted to cecorrhaphy
Authors: Ávila Filho S. H. , Moura V. M. B. D. , Queiroz P. J. B. , Faleiro M. B. R. , Lima B. S. G. , Freitas S. L. R. , Santos A. S. , Silva L. A. F.
Published: August 2023

The development and evaluation of synthesis materials are crucial to reducing the morbidity and magnitude of post‐enterorrhaphy surgical complications. Despite the possibility of production, chitosan thread has not yet been used in enterorrhaphy, and its effects on intestinal healing have not been evaluated. Therefore, this study aimed to evaluate the effects of chitosan thread on the intestinal wall repair of rabbits submitted to cecorrhaphy. For this, 42 rabbits were allocated into two groups with 21 animals. One group was submitted to cecorrhaphy with chitosan suture thread (CG) and the other with poliglecaprone suture thread (PG). The occurrence of postoperative complications, the intensity of edema, cellular response, formation of granulation tissue, as well as the deposition and maturation of collagen fibers, and the intensity of vascular endothelial growth factor (VEGF‐α) expression, were evaluated during the intestinal wall repair process. The evaluations occurred on the 5th, 15th, and 25th postoperative (PO) days. The animals did not develop peritonitis, but adherence was observed in six animals from CG and seven from PG, with no difference between groups. The polymorphonuclear infiltrate showed higher intensity and higher amount of type III collagen fibers in CG on the 15th PO day. In contrast, a lower amount of type I collagen fibers was observed in CG samples on the 25th PO day. Therefore, the chitosan thread used for cecorrhaphy in rabbits results in minimal postoperative complications, presents biocompatibility, and bioactively assists the tissue repair process of the cecal wall, inducing minimal tissue reaction, stimulating the deposition of type III collagen fibers in the proliferative phase, with sustained VEGF‐α expression, but with reduced deposition of type I fibers, indicating a delay in collagen maturation.
Antidiabetic activity of eupafolin through peroxisome proliferator‐activated receptor‐gamma and PI3K/Akt signaling in Type 2 diabetic rats
Authors: Wu Su , Ai Wenwei , Nie Lei , Lu Xiao
Published: August 2023

Eupafolin is a phyto compound of flavone that exerts anti‐inflammatory, antioxidant, and antiproliferative properties. The main purpose of this study is to examine the antidiabetic effect of eupafolin on nicotinamide–streptozotocin (STZ)‐induced Type 2 diabetes (T2D) rats. After nicotinamide (120 mg/kg) treatment, STZ (60 mg/kg) was administrated intravenously to induce T2D. Rats with fasting blood glucose (FBG) > 200 mg/dL are chosen for the study 7 days after T2D induction. The eupafolin treatment was continued for another 15 days. FBG and an oral glucose tolerance test (OGTT) were measured on the 21st day after T2D induction. The blood lipid, serum insulin, and homeostatic model assessment (HOMA‐IR) were determined. In liver homogenate, oxidative stress indicators were measured. In addition, the effect of eupafolin on the expression of the proteins InsR, insulin receptor substrate (IRS)‐2, GLUT4, PPARγ, and phosphatidylinositol 3‐kinase (PI3K)/Akt was investigated using a western blot. As measured by OGTT and HOMA‐IR, eupafolin treatment reduced FBG and insulin resistance (IR). Furthermore, when compared to diabetic rats, liver antioxidant enzymes were dramatically normalized. The level of glycogen in the liver of diabetic rats was increased by eupafolin treatment. In T2D rats, eupafolin dramatically increased the InsR, IRS‐2, GLUT4, and PPARγ. Further, the eupafolin treatment activated the PI3K/Akt signaling in T2D rats. These findings imply that the antidiabetic mechanism of eupafolin may be related to the activation of the PPARγ and the PI3K/Akt signaling pathway in T2D rats. As a result, the flavonoid eupafolin could be an antidiabetic medication for T2D after a comprehensive clinical investigation.
Gemcitabine resistance in non‐small cell lung cancer is mediated through activation of the PI3K/AKT/NF‐κB pathway and suppression of ERK signaling by reactive oxygen species
Authors: Chiu Chih‐Hao , Lin Yu‐Jung , Ramesh Samiraj , Kuo Wei‐Wen , Chen Ming‐Cheng , Kuo Chia‐Hua , Li Chi‐Cheng , Wang Tso‐Fu , Lin Yueh‐Min , Liao Po‐Hsiang , Huang Chih‐Yang
Published: August 2023

Lung cancer is one of the most common cancers in the world. Chemotherapy is a standard clinical treatment. However, tumor cells often develop multidrug resistance after chemotherapy, an inevitable bottleneck in cancer treatment. Therefore, this study used gemcitabine‐resistant (GEM‐R) CL1‐0 lung cancer cells. First, we used flow cytometry and western blot analysis to examine differences in performance between resistant and parental cells. The results showed that compared with parental cells, GEM‐R CL1‐0 cells significantly enhanced the activation of the AKT pathway, which promoted survival and growth, and decreased the activation of the reactive oxygen species‐extracellular signal‐regulated kinase (ROS)‐ERK pathway. Next, the AKT and ERK pathways' role in tumor growth was further explored in vivo using a xenograft model. The results showed that enhancing AKT and inhibiting ERK activation reduced GEM‐induced inhibition of tumor growth. Finally, combining the above results, we found that GEM‐R CL1‐0 cells showed reduced sensitivity to GEM by activating the phosphatidylinositol 3‐kinase/AKT/NF‐kB pathway and inhibiting the ROS‐ERK pathway leading to resistance against GEM. Therefore, the AKT and ERK pathways are potential targets for improving the sensitivity of cancer cells to anticancer drugs.
Novel chemical scaffold as potential drug against Leishmania donovani: Integrated computational and experimental approaches
Authors: Ranjan Preeti , Dubey Vikash Kumar
Published: August 2023

In this study, we have screened a large number of Food and Drug Administration‐approved compounds for novel anti‐leishmanial molecules targeting the citrate synthase enzyme of the parasite. Based on their docking and molecular dynamic simulation statistics, five compounds were selected. These compounds followed Lipinski's rule of five. Additionally, in vitro, antileishmanial and cytotoxicity studies were performed. The three compounds, Abemaciclib, Bazedoxifene, and Vorapaxar, had shown effective anti‐leishmanial activities with IC50 values of 0.92 ± 0.02, 0.65 ± 0.09, and 6.1 ± 0.91 against Leishmania donovani promastigote and with EC50 values of 1.52 ± 0.37, 2.11 ± 0.38, 10.4 ± 1.27 against intramacrophagic amastigote without significantly harming macrophage cells. Among them, from in silico and antileishmanial activities studies, Abemaciclib had been selected based on their less binding energy, good antileishmanial activities, and also a significant difference in their binding energy with human citrate synthase for cell death mechanistic studies using flow cytometry and a DNA fragmentation assay. The action of this compound resulted in an increased reactive oxygen species production, depolarization of mitochondrial membrane potential, DNA damage, and an increase in the sub‐G1 cell population. These properties are the hallmarks of apoptosis which were further confirmed by apoptotic assay. Based on the above result, this anticancer compound Abemaciclib could be employed as a potential treatment option for leishmaniasis after further confirmation.
Rab44 negatively regulates myoblast differentiation by controlling fusogenic protein transport and mTORC1 signaling
Authors: Tanimoto Ayuko , Yamaguchi Yu , Kadowaki Tomoko , Sakai Eiko , Oyakawa Shun , Ono Yusuke , Yoshida Noriaki , Tsukuba Takayuki
Published: August 2023

Skeletal muscle is composed of multinucleated myotubes formed by the fusion of mononucleated myoblasts. Skeletal muscle differentiation, termed as myogenesis, have been investigated using the mouse skeletal myoblast cell line C2C12. It has been reported that several “small” Rab proteins, major membrane‐trafficking regulators, possibly regulate membrane protein transport in C2C12 cells; however, the role of Rab proteins in myogenesis remains unexplored. Rab44, a member of “large” Rab GTPases, has recently been identified as a negative regulator of osteoclast differentiation. In this study, using C2C12 cells, we found that Rab44 expression was upregulated during myoblast differentiation into myotubes. Knockdown of Rab44 enhanced myoblast differentiation and myotube formation. Consistent with these results, Rab44 knockdown in myoblasts increased expression levels of several myogenic marker genes. Rab44 knockdown increased the surface accumulation of myomaker and myomixer, two fusogenic proteins required for multinucleation, implying enhanced cell fusion. Conversely, Rab44 overexpression inhibited myoblast differentiation and tube formation, accompanied by decreased expression of some myogenic markers. Furthermore, Rab44 was found to be predominantly localized in lysosomes, and Rab44 overexpression altered the number and size of lysosomes. Considering the underlying molecular mechanism, Rab44 overexpression impaired the signaling pathway of the mechanistic target of rapamycin complex1 (mTORC1) in C2C12 cells. Namely, phosphorylation levels of mTORC1 and downstream mTORC1 substrates, such as S6 and P70‐S6K, were notably lower in Rab44 overexpressing cells than those in control cells. These results indicate that Rab44 negatively regulates myoblast differentiation into myotubes by controlling fusogenic protein transport and mTORC1 signaling.
The emerging era of lactate: A rising star in cellular signaling and its regulatory mechanisms
Authors: Wu Di , Zhang Kejia , Khan Faheem Ahmed , Wu Qin , Pandupuspitasari Nuruliarizki Shinta , Tang Yuan , Guan Kaifeng , Sun Fei , Huang Chunjie
Published: August 2023

Cellular metabolites are ancient molecules with pleiotropic implications in health and disease. Beyond their cognate roles, they have signaling functions as the ligands for specific receptors and the precursors for epigenetic or posttranslational modifications. Lactate has long been recognized as a metabolic waste and fatigue product mainly produced from glycolytic metabolism. Recent evidence however suggests lactate is an unique molecule with diverse signaling attributes in orchestration of numerous biological processes, including tumor immunity and neuronal survival. The copious metabolic and non‐metabolic functions of lactate mediated by its bidirectional shuttle between cells or intracellular organelles lead to a phenotype called “lactormone.” Importantly, the mechanisms of lactate signaling, via acting as a molecular sensor and a regulator of NAD+ metabolism and AMP‐activated protein kinase signaling, and via the newly identified lactate‐driven lactylation, have been discovered. Further, we include a brief discussion about the autocrine regulation of efferocytosis by lactate in Sertoli cells which favoraerobic glycolysis. By emphasizing a repertoire of the most recent discovered mechanisms of lactate signaling, this review will open tantalizing avenues for future investigations cracking the regulatory topology of lactate signaling covered in the veil of mystery.
Evolutionarily conserved heat shock protein, HtpX, as an adjunct target against antibiotic‐resistant Neisseria gonorrhoeae
Authors: Vashishtha Shubham , Thakur Sheetal , Singh Jasdeep , Adhana Sujata , Kundu Bishwajit
Published: August 2023

The emergence of multiple drug resistance and extreme drug resistance pathogens necessitates the continuous evaluation of the pathogenic genome to identify conserved molecular targets and their respective inhibitors. In this study, we mapped the global mutational landscape of Neisseria gonorrhoeae (an intracellular pathogen notoriously known to cause the sexually transmitted disease gonorrhoea). We identified highly variable amino acid positions in the antibiotic target genes like the penA, ponA, 23s rRNA, rpoB, gyrA, parC, mtrR and porB. Some variations are directly reported to confer resistance to the currently used front‐line drugs like ceftriaxone, cefixime, azithromycin and ciprofloxacin. Further, by whole genome comparison and Shannon entropy analysis, we identified a completely conserved protein HtpX in the drug‐resistant as well as susceptible isolates of N. gonorrhoeae (NgHtpX). Comparison with the only available information of Escherichia coli HtpX suggested it to be a transmembrane metalloprotease having a role in stress response. The critical zinc‐binding residue of NgHtpX was mapped to E141. By applying composite high throughput screening followed by MD simulations, we identified pemirolast and thalidomide as high‐energy binding ligands of NgHtpX. Following cloning and expression of the purified metal‐binding domain of NgHtpX (NgHtpXd), its Zn2+‐binding (Kd = 0.4 µM) and drug‐binding (pemirolast, Kd = 3.47 µM; and thalidomide, Kd = 1.04 µM) potentials were determined using in‐vitro fluorescence quenching experiment. When tested on N. gonorrhoeae cultures, both the ligands imposed a dose‐dependent reduction in viability. Overall, our results provide high entropy positions in the targets of presently used antibiotics, which can be further explored to understand the AMR mechanism. Additionally, HtpX and its specific inhibitors identified can be utilised effectively in managing gonococcal infections.
STAIR Narrative Therapy for complex posttraumatic stress disorder: Treating sexual and gender minority trauma
Authors: Cloitre Marylene , Lovelund Adrienne A. , Jackson Christie , Edward Donovan , Baker Michelanne
Published: August 2023

Background

Complex PTSD is a recent addition to the ICD‐11 diagnostic system.

Aims

This case study describes the delivery of Skills Training in Affective and Interpersonal Regulation and Narrative Therapy (SNT), a flexible, multi‐component therapy that addresses the symptoms of complex posttraumatic stress disorder. SNT balances interventions that address current‐day stressors with those that reappraise the meaning of traumatic past events. This paper outlines 16 sessions of SNT with a 55‐year‐old gay man.

Discussion

The case analysis describes the ways in which SNT is relevant and effective in addressing the client's mulitple concerns. The skills work helped the client effectively  manage ongoing minority stress, discrimination, and micro‐aggressions related to his identity as a gay man. Review and re‐appraisal of his traumatic memories, which focused on the sudden death of his partner from AIDS along with discussion of events from his childhood that shaped his reactions to this loss, allowed the client to create a more integrated sense of self as well as a more compassionate view of himself. Implications regarding the relevance of SNT for sexual and gender minority individuals are discussed.
Programmed cell death of periodontal ligament cells
Authors: He Wei , Fu Yu , Yao Song , Huang Lan
Published: August 2023

The periodontal ligament is a crucial tissue that provides support to the periodontium. Situated between the alveolar bone and the tooth root, it consists primarily of fibroblasts, cementoblasts, osteoblasts, osteoclasts, periodontal ligament stem cells (PDLSCs), and epithelial cell rests of Malassez. Fibroblasts, cementoblasts, osteoblasts, and osteoclasts are functionally differentiated cells, whereas PDLSCs are undifferentiated mesenchymal stem cells. The dynamic development of these cells is intricately linked to periodontal changes and homeostasis. Notably, the regulation of programmed cell death facilitates the clearance of necrotic tissue and plays a pivotal role in immune response. However, it also potentially contributes to the loss of periodontal supporting tissues and root resorption. These findings have significant implications for understanding the occurrence and progression of periodontitis, as well as the mechanisms underlying orthodontic root resorption. Further, the regulation of periodontal ligament cell (PDLC) death is influenced by both systemic and local factors. This comprehensive review focuses on recent studies reporting the mechanisms of PDLC death and related factors.
CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy‐dependent ferroptosis
Authors: Shang Ziqi , Luo Zhengdong , Wang Yifeng , Liu Qi , Xin Yiwei , Zhang Mengjiao , Li Xinyang , Zeng Shunjie , Yu Longchen , Zhang Xin , Zhang Yi
Published: August 2023

Cisplatin is the first‐line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy‐dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR‐508‐3p/Bcl‐2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.
Transformed cells maintain survival by downregulating autophagy at a high cell confluency
Authors: Kim Hye‐Gyo , Ro Myeong‐Han , Hwang Sung‐Hee , Lee Michael
Published: August 2023

Autophagy plays a dual role in tumorigenesis by functioning as both a tumor suppressor and promoter, depending on the stage of tumorigenesis. However, it is still unclear at what stage the role of autophagy changes during tumorigenesis. Herein, we investigated the differences in the basal levels and roles of autophagy in five cell lines at different stages of cell transformation. We found that cell lines at higher transformation stages were more sensitive to the autophagy inhibitors, suggesting that autophagy plays a more important role as the transformation progresses. Our ptfLC3 imaging analysis to measure Atg5/LC3‐dependent autophagy showed increased autophagic flux in transformed cells compared to untransformed cells. However, the Cyto‐ID analysis, which measures Atg5‐dependent and ‐independent autophagic flux, showed high levels of autophagosome formation not only in the transformed cells but also in the initiated cell and Atg5 KO cell line. These results indicate that Atg5‐independent autophagy may be more critical in initiated and transformed cell lines than in untransformed cells. Specially, we observed that transformed cells maintained relatively high basal autophagy levels under rapidly proliferating conditions but exhibited much lower basal autophagy levels at high confluency; however, autophagic flux was not significantly reduced in untransformed cells, even at high confluency. In addition, when continuously cultured for 3 weeks without passage, senescent cells were significantly less sensitive to autophagy inhibition than their actively proliferating counterparts. These results imply that once a cell has switched from a proliferative state to a senescent state, the inhibition of autophagy has only a minimal effect. Taken together, our results suggest that autophagy can be differentially regulated in cells at different stages of tumorigenesis under stressful conditions.
Association between the 110‐kDa C‐terminal agrin fragment and skeletal muscle decline among community‐dwelling older women
Authors: Kamiya Kuniyasu , Tachiki Takahiro , Sato Yuho , Kouda Katsuyasu , Kajita Etsuko , Tamaki Junko , Kagamimori Sadanobu , Iki Masayuki
Published: August 2023

Background

C‐terminal agrin fragment (CAF) is a biomarker for neuromuscular junction degradation. This study aimed to investigate whether 110‐kDa CAF (CAF110) was associated with the presence and incidence of low muscle mass and strength.

Methods

This cross‐sectional retrospective cohort study comprised women aged ≥65 years. We measured muscle mass using a dual‐energy X‐ray absorptiometry scanner, hand‐grip strength, and blood sampling between 2011 and 2012. A follow‐up study with the same measurements was conducted between 2015 and 2017. Low muscle mass and strength were defined as an appendicular skeletal muscle mass index <5.4 kg/m2 and hand‐grip strength <18 kg, respectively. The CAF110 level was measured using enzyme‐linked immunosorbent assay kits.

Results

In total, 515 women (74.3 ± 6.3 years) were included in this cross‐sectional analysis. Of these, 101 (19.6%) and 128 (24.9%) women presented with low muscle mass and strength, respectively. For low muscle mass, the odds ratios (ORs) of the middle and highest CAF110 tertile groups, compared with the lowest group, were 1.93 (95% confidence interval: 1.09–3.43; P = 0.024) and 2.15 (1.22–3.80; P = 0.008), respectively. After adjusting for age, the ORs remained significant: 1.98 (1.11–3.52; P = 0.020) and 2.27 (1.28–4.03; P = 0.005), respectively. Low muscle strength ORs of all the CAF110 tertile groups were not significant. In the longitudinal analysis, 292 and 289 women were assessed for incidents of low muscle mass and strength, respectively. Of those, 34 (11.6%) and 20 (6.9%) women exhibited low muscle mass and strength, respectively. For incident low muscle mass, the crude OR of the CAF110 ≥ the median value group was marginally higher than that of the CAF110 < median value group (median [interquartile range]: 1.98 [0.94–4.17] (P = 0.072). After adjusting for age and baseline muscle mass, the OR was 2.22 [0.97–5.06] (P = 0.058). All low muscle strength ORs of the median categories of CAF110 were not significant.

Conclusions

CAF110 was not associated with low muscle strength. However, CAF110 may be a potential marker for the incidence of low muscle mass.
Attitudes and opinions of telehealth in the dental school environment: A survey study
Authors: Bakerywala Arifa , Finkelman Matthew , Swee Gerald , Lerman Mark , Loo Cheen Y.
Published: August 2023

Purpose

The objective of this study was to assess provider attitudes and opinions regarding telehealth in the dental school environment.

Method

A survey was developed and validated and was sent to 849 predoctoral students, postdoctoral students (residents), and faculty at a single dental school. It consisted of 13 questions regarding the participants’ professional backgrounds, opinions, and attitudes toward telehealth. The survey opened on November 16, 2021, and remained open for 6 weeks.

Results

Of 849 survey recipients, 163 (19%) responded. Among 161 usable surveys, 90 (56%) were predoctoral students, 42 (26%) were postdoctoral students, and 29 (18%) were faculty. Fifty‐four percent reported having completed at least one telehealth visit. Among this subset, 80% strongly agreed or agreed that telehealth is a good adjunct in providing care; 74% strongly agreed or agreed that telehealth has improved communication with patients.

Conclusion

Most dental providers reported positive opinions and attitudes regarding telehealth's ability to improve communication and serve as an adjunct to providing care.

Practical implications

In the right circumstances, telehealth offers an alternative to traditional oral healthcare delivery methods. Based on the perceptions of dental providers, the use of telehealth may also be beneficial in combination with traditional approaches in the dental school environment.
Brain metastases from breast cancer using magnetic resonance imaging: A systematic review
Authors: Mohammadi Mahdi , Mohammadi Sana , Hadizadeh Hojatollah , Olfati Mahsa , Moradi Fatemeh , Tanzifi Ghazal , Ghaderi Sadegh
Published: August 2023

Despite improvements in imaging and treatment approaches, brain metastases (BMs) continue to be the primary cause of mortality and morbidity in about 20% of adult cancer patients. This research aimed to review the magnetic resonance imaging (MRI) and clinical characteristics of BMs resulting from breast cancer (BC). A systematic review of original research articles published from January 2000 to June 2023. We selected studies that reported MRI findings of BMs in BC patients. We excluded reviews, case reports, books/book chapters, animal studies and irrelevant records. We identified 24 studies that included 1580 BC patients with BMs. T1‐weighted (T1‐w) (pre‐ and postcontrast), T2‐weighted (T2‐w), fluid‐attenuated inversion recovery (FLAIR) and T2*‐weighted (T2*‐w) was used to measure the lesion size, shape and area. In other studies, advanced structural techniques including diffusion‐weighted imaging (DWI), diffusion tensor imaging (DTI) and susceptibility‐weighted imaging (SWI) were used to more precisely and sensitively evaluate the pathological area. Furthermore, functional and metabolic techniques like functional MRI (fMRI), magnetic resonance spectroscopy (MRS) and perfusion‐weighted imaging (PWI) have also been utilised. The MRI findings of BMs varied depending on the MRI technique, the BC subtype, the lesion size and shape, the presence of haemorrhage or necrosis and the comparison with other brain tumours. Some MRI findings were associated with prognosis, recurrence or cognitive impairment in BC patients with BMs. MRI detects, characterises and monitors BMs from BC. Findings vary by MRI technique, BC subtype, lesion characteristics and comparison with other brain tumours. More research should validate emerging MRI techniques, determine the clinical implications of findings and explore the underlying mechanisms and biology of BMs from BC. MRI is a valuable tool for diagnosis, targeted therapy and studying BC metastasis.
Implementation and clinical evaluation of an Mpox virus laboratory‐developed test on a fully automated random‐access platform
Authors: Wettengel Jochen M. , Bunse Till , Jeske Samuel D. , Wölfel Roman , Zange Sabine , Taeubner Julia , Goelnitz Uta , Protzer Ulrike
Published: August 2023

While Mpox virus (MPXV) diagnostics were performed in specialized laboratories only, the global emergence of Mpox cases in 2022 revealed the need for a more readily available diagnostic. Automated random‐access platforms with fast nucleic acid extraction and PCR have become established in many laboratories, providing faster and more accessible testing. In this study, we adapted a previously published generic MPXV‐PCR as a lab‐developed test (LDT) on a NeuMoDx Molecular System and isolated MPXV clones from patient materials. To reduce the handling of infectious material, we evaluated a viral lysis buffer (VLB) for sample pretreatment. We further compared the MPXV‐LDT‐PCR to conventional real‐time PCR, determined its sensitivity and specificity using positive swabs, and assessed its performance using external quality assessment samples. Pretreatment of samples with 50% VLB reduced MPXV infectivity by approximately 200‐fold while maintaining PCR sensitivity. The assay demonstrated a sensitivity and specificity of 100% with no cross‐reactivity in the samples tested and performed with a limit of detection of 262 GE/mL. In summary, the assay had a turnaround time of fewer than 2 h and can easily be transferred to other automated PCR platforms, providing a basis for developing rapid assays for upcoming pandemics.
CREB1 activation promotes human papillomavirus oncogene expression and cervical cancer cell transformation
Authors: Li Yigen , Patterson Molly R. , Morgan Ethan L. , Wasson Christopher W. , Ryder Emma L. , Barba‐Moreno Diego , Scarth James A. , Wang Miao , Macdonald Andrew
Published: August 2023

Human papillomaviruses (HPVs) infect the oral and anogenital mucosa and can cause cancer. The high‐risk (HR)‐HPV oncoproteins, E6 and E7, hijack cellular factors to promote cell proliferation, delay differentiation and induce genomic instability, thus predisposing infected cells to malignant transformation. cAMP response element (CRE)‐binding protein 1 (CREB1) is a master transcription factor that can function as a proto‐oncogene, the abnormal activity of which is associated with multiple cancers. However, little is known about the interplay between HPV and CREB1 activity in cervical cancer or the productive HPV lifecycle. We show that CREB is activated in productively infected primary keratinocytes and that CREB1 expression and phosphorylation is associated with the progression of HPV+ cervical disease. The depletion of CREB1 or inhibition of CREB1 activity results in decreased cell proliferation and reduced expression of markers of epithelial to mesenchymal transition, coupled with reduced migration in HPV+ cervical cancer cell lines. CREB1 expression is negatively regulated by the tumor suppressor microRNA, miR‐203a, and CREB1 phosphorylation is controlled through the MAPK/MSK pathway. Crucially, CREB1 directly binds the viral promoter to upregulate transcription of the E6/E7 oncogenes, establishing a positive feedback loop between the HPV oncoproteins and CREB1. Our findings demonstrate the oncogenic function of CREB1 in HPV+ cervical cancer and its relationship with the HPV oncogenes.
Perovskites informatics: Studying the impact of thicknesses, doping, and defects on the perovskite solar cell efficiency using a machine learning algorithm
Authors: Ismail Zahraa S. , Sawires Eman F. , Amer Fathy Z. , Abdellatif Sameh O.
Published: August 2023

The integration of machine learning (ML) models in studying, investigating, and optimizing various electronic devices and materials has significantly glow up. With the aid of ML algorithms and input datasets, data regression and prediction can show the output characteristic performance under a wide range of input combinations. Herein, we utilize a random‐forest ML algorithm to study the influence of nine input design parameters on the overall power conversion efficiency (PCE) of cesium lead halides perovskites cells. The doping levels, the defects densities, and the thicknesses among the perovskite thin film, as well as the hole and electron transport layers, are studied against the cell PCE. The seeded dataset is managed using experimental data and experimentally validated numerical simulations. Datasets of more than 1 512 000 points were generated and seeded to the ML model. The PCE variation against the inputs for the three metal halides was investigated. A 17.8% PCE for CsPbI3 was reached, while PCE of 14.6% and 6.5% were recorded for CsPbBr3, and CsPbCl3, respectively.
New targets of TetR‐type regulator SLCG_2919 for controlling lincomycin biosynthesis in Streptomyces lincolnensis
Authors: Xu Yurong , Yi Jing , Kai Yuanzhong , Li Binglin , Liu Meng , Zhou Qihua , Wang Jingru , Liu Ruihua , Wu Hang
Published: August 2023

The transcription factor (TF)‐mediated regulatory network controlling lincomycin production in Streptomyces lincolnensis is yet to be fully elucidated despite several types of associated TFs having been reported. SLCG_2919, a tetracycline repressor (TetR)‐type regulator, was the first TF to be characterized outside the lincomycin biosynthetic cluster to directly suppress the lincomycin biosynthesis in S. lincolnensis. In this study, improved genomic systematic evolution of ligands by exponential enrichment (gSELEX), an in vitro technique, was adopted to capture additional SLCG_2919‐targeted sequences harboring the promoter regions of SLCG_6675, SLCG_4123‐4124, SLCG_6579, and SLCG_0139‐0140. The four DNA fragments were confirmed by electrophoretic mobility shift assays (EMSAs). Reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) showed that the corresponding target genes SLCG_6675 (anthranilate synthase), SLCG_0139 (LysR family transcriptional regulator), SLCG_0140 (beta‐lactamase), SLCG_6579 (cytochrome P450), SLCG_4123 (bifunctional DNA primase/polymerase), and SLCG_4124 (magnesium or magnesium‐dependent protein phosphatase) in ΔSLCGL_2919 were differentially increased by 3.3‐, 4.2‐, 3.2‐, 2.5‐, 4.6‐, and 2.2‐fold relative to those in the parental strain S. lincolnensis LCGL. Furthermore, the individual inactivation of these target genes in LCGL reduced the lincomycin yield to varying degrees. This investigation expands on the known DNA targets of SLCG_2919 to control lincomycin production and lays the foundation for improving industrial lincomycin yields via genetic engineering of this regulatory network.
Reference evapotranspiration during the growing season in Poland (central Europe) in response to ongoing climate changes (1966–2020)
Authors: Araźny Andrzej , Kępińska‐Kasprzak Małgorzata , Łaszyca Edward Zbigniew , Chmist‐Sikorska Joanna , Bartczak Arkadiusz
Published: August 2023

Evapotranspiration is an important part of the water cycle and influences, for example, water management and agricultural production. The article presents temporal and spatial changes in reference evapotranspiration (ETo) in the growing season (April–September) against the background of climatic conditions in Poland in the years 1966–2020. ETo was calculated using the Penman–Monteith method using data from 37 meteorological stations in the network of the Institute of Meteorology and Water Management‐National Research Institute. For the growing season of April–September, the average sum of ETo for Poland was 529 mm. In terms of spatial distribution, the values were lowest in northern Poland (Kołobrzeg, 480 mm; Lębork, 488 mm) and highest in the central lowlands (Warsaw, 570 mm; Poznań, 566 mm). For individual months, the average sum of ETo ranged from 53 to 63 mm in April and September to 108–112 mm in June and July. In Poland, in the years 1966–2020, ETo showed a statistically significant upward trend of 16.4 mm/10 year. This is the result of, inter alia, statistically significant increases in sunshine duration and air temperature and a decrease in relative humidity (respectively: 62 h/10 year, 0.40°C/10 year and −1%/10 year) during the growing season in Poland. Within the multiyear study period, the maximum ETo values occurred in 2018, reaching values of >700 mm. At that time, Poland was under the influence of very intense anticyclonic circulation. This is confirmed by the relationship between ETo and the anticyclonic circulation index for central Poland, which is statistically significant for the 55 study years.
Reconstruction of oncologic upper extremity defects with fibula free flaps has high union rates and excellent functional outcomes
Authors: Shahzad Farooq , Fazzalari Amanda , Zoghbi Yasmina , Coriddi Michelle R. , Chapman Talia R. , Mehrara Babak J. , Disa Joseph J. , Cordeiro Peter G. , Healey John , Athanasian Edward
Published: August 2023

Background

Limb salvage has better functional outcomes than amputation in the upper extremity. This can however be challenging after bony tumor resections.

Methods

This is a retrospective case series of patients who underwent humerus, ulna, or radius reconstruction with a fibula free flap. Data were collected on demographics, oncologic history, surgical details, and complications. Functional outcome measures included the patient's ability to perform activities of daily living (ADL), presence of pain, and musculoskeletal tumor society (MSTS) score.

Results

Over a 25‐year period, 38 reconstructions were performed. The flap success rate was 97.5%. Bony union was obtained in 19 of 19 (100%) forearm reconstructions and in 15 of 19 (79%) humerus reconstructions (p = 0.10). All 19 forearm reconstruction patients and 18/19 humerus reconstruction patients were able to perform ADLs with no pain or only occasional pain. The MSTS scores were not significantly different between the humerus and forearm cohorts (27.1 vs. 27.3, p = 0.68). Functional outcomes were significantly better in limbs that achieved union (p < 0.001). Recipient and donor site complications occurred in 10 (26.3%) and 5 (13%) patients, respectively.

Conclusions

Oncologic upper‐extremity reconstruction with fibula free flaps has excellent functional outcomes. Bone union is a predictor of superior limb function.
Relationship between blood lead levels and clinical and physiological factors in Bonelli's eagle
Authors: Villén‐Molina Elisa , Rodríguez Casilda , López Irene , Suárez Laura , Moraleda Virginia , González Fernando
Published: August 2023

Lead is a toxic metal that produces effects on the overall health of animals, resulting in mortality at high exposures, adverse physiological and behavioral effects at lower concentrations, and population declines in many species. Scavengers and predators are more susceptible to lead toxicity because of behavioral and physiologic factors, and long lifespans increase the risk of exposure cumulatively. Bonelli's eagle (Aquila fasciata) is a long‐living predator that may have reduced breeding success because of lead exposure. We analyzed the blood lead levels of 54 wild and captive Bonelli's eagles admitted to a recovery center in Spain from May 2014 to July 2015 and the lead relationship among physiological, clinical, and environmental variables. We detected blood lead using anodic stripping voltammetry. Lead levels were below the limit of quantification (3.3 μg/dL) in 100% of captive animals (n = 22); in contrast, 21.9% of wild birds (n = 32) had higher lead levels than captive birds (P = 0.020). Among wild animals, the 2 adults tested had detectable lead, the only eagle sampled in autumn had the highest lead levels of the study (14.7 μg/dL), and 16.7% of nestlings had detectable lead levels. There is no evidence that the lead levels differ between sexes. There were no symptoms associated with lead intoxication or any correlation between lead levels and hematological or biochemical values; however, subclinical lead exposure at early ages can be harmful and could influence neurological and body development. Researchers should determine if lead could be causing damage to wildlife from early ages to determine if lead exposure affects the conservation of the threatened population of Bonelli's eagles in Spain and elsewhere.