bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptomic profiling reveals the tumor heterogeneity of small-cell lung cancer
Authors: Tian Yanhua , Li Qingqing , Yang Zhenlin , Zhang Shu , Xu Jiachen , Wang Zhijie , Bai Hua , Duan Jianchun , Zheng Bo , Li Wen , Cui Yueli , Wang Xin , Wan Rui , Fei Kailun , Zhong Jia , Gao Shugeng , He Jie , Gay Carl M. , Zhang Jianjun , Wang Jie , Tang Fuchou 
Published: October 2022

AbstractSmall-cell lung cancer (SCLC) is the most aggressive and lethal subtype of lung cancer, for which, better understandings of its biology are urgently needed. Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment (TME) and investigate their roles in tumorigenic processes. Here, we performed high-precision single-cell transcriptomic analysis of ~5000 individual cells from primary tumors (PTs) and matched normal adjacent tissues (NATs) from 11 SCLC patients, including one patient with both PT and relapsed tumor (RT). The comparison revealed an immunosuppressive landscape of human SCLC. Malignant cells in SCLC tumors exhibited diverse states mainly related to the cell cycle, immune, and hypoxic properties. Our data also revealed the intratumor heterogeneity (ITH) of key transcription factors (TFs) in SCLC and related gene expression patterns and functions. The non-neuroendocrine (non-NE) tumors were correlated with increased inflammatory gene signatures and immune cell infiltrates in SCLC, which contributed to better responses to immune checkpoint inhibitors. These findings indicate a significant heterogeneity of human SCLC, and intensive crosstalk between cancer cells and the TME at single-cell resolution, and thus, set the stage for a better understanding of the biology of SCLC as well as for developing new therapeutics for SCLC.
The clinical management of testosterone replacement therapy in postmenopausal women with hypoactive sexual desire disorder: a review
Authors: Uloko Maria , Rahman Farah , Puri Leah Ibrahim , Rubin Rachel S. 
Published: October 2022

AbstractAs women age, there is an overall decrease in androgen production due to decline of ovarian and adrenal function during menopause. Androgens have been demonstrated to play an important role in sexual motivation in women. As a result, many postmenopausal women experience Female Sexual Dysfunction (FSD) which are a group of disorders that pertain to sexual arousal, desire, orgasm, and pain. A prevalent manifestation of FSD is Hypoactive Sexual Desire Disorder (HSDD) or the absence of sexual fantasies, thoughts, and/or desire for or receptivity to sexual activity. There is gaining interest in the use of Testosterone Replacement Therapy (TRT) for the treatment of HSDD in postmenopausal women. This article reviews the literature on the relationship of androgen decline and HSDD, describes our methodology for evaluation, diagnosis of HSDD, and the use of TRT in treating postmenopausal women with HSDD. Our results conclude that testosterone is a vital hormone in women in maintaining sexual health and function. TRT is an effective treatment option for postmenopausal people with HSDD. There is still limited data on the effectiveness in premenopausal people with HSDD. Further research in the strengths and weaknesses for the long-term effect of TRT in women of all ages is needed.
Deletion of skeletal muscle Akt1/2 causes osteosarcopenia and reduces lifespan in mice
Authors: Sasako Takayoshi , Umehara Toshihiro , Soeda Kotaro , Kaneko Kazuma , Suzuki Miho , Kobayashi Naoki , Okazaki Yukiko , Tamura-Nakano Miwa , Chiba Tomoki , Accili Domenico , Kahn C. Ronald , Noda Tetsuo , Asahara Hiroshi , Yamauchi Toshimasa , Kadowaki Takashi , Ueki Kohjiro 
Published: October 2022

AbstractAging is considered to be accelerated by insulin signaling in lower organisms, but it remained unclear whether this could hold true for mammals. Here we show that mice with skeletal muscle-specific double knockout of Akt1/2, key downstream molecules of insulin signaling, serve as a model of premature sarcopenia with insulin resistance. The knockout mice exhibit a progressive reduction in skeletal muscle mass, impairment of motor function and systemic insulin sensitivity. They also show osteopenia, and reduced lifespan largely due to death from debilitation on normal chow and death from tumor on high-fat diet. These phenotypes are almost reversed by additional knocking out of Foxo1/4, but only partially by additional knocking out of Tsc2 to activate the mTOR pathway. Overall, our data suggest that, unlike in lower organisms, suppression of Akt activity in skeletal muscle of mammals associated with insulin resistance and aging could accelerate osteosarcopenia and consequently reduce lifespan.
Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis
Authors: Aguilar Carmen , Pauzuolis Mindaugas , Pompaiah Malvika , Vafadarnejad Ehsan , Arampatzi Panagiota , Fischer Mara , Narres Dominik , Neyazi Mastura , Kayisoglu Özge , Sell Thomas , Blüthgen Nils , Morkel Markus , Wiegering Armin , Germer Christoph-Thomas , Kircher Stefan , Rosenwald Andreas , Saliba Antoine-Emmanuel , Bartfeld Sina 
Published: October 2022

AbstractThe human gastric epithelium forms highly organized gland structures with different subtypes of cells. The carcinogenic bacterium Helicobacter pylori can attach to gastric cells and subsequently translocate its virulence factor CagA, but the possible host cell tropism of H. pylori is currently unknown. Here, we report that H. pylori preferentially attaches to differentiated cells in the pit region of gastric units. Single-cell RNA-seq shows that organoid-derived monolayers recapitulate the pit region, while organoids capture the gland region of the gastric units. Using these models, we show that H. pylori preferentially attaches to highly differentiated pit cells, marked by high levels of GKN1, GKN2 and PSCA. Directed differentiation of host cells enable enrichment of the target cell population and confirm H. pylori preferential attachment and CagA translocation into these cells. Attachment is independent of MUC5AC or PSCA expression, and instead relies on bacterial TlpB-dependent chemotaxis towards host cell-released urea, which scales with host cell size.
Thermosensation in Caenorhabditis elegans is linked to ubiquitin-dependent protein turnover via insulin and calcineurin signalling
Authors: Segref Alexandra , Vakkayil Kavya L. , Padvitski Tsimafei , Li Qiaochu , Kroef Virginia , Lormann Jakob , Körner Lioba , Finger Fabian , Hoppe Thorsten 
Published: October 2022

AbstractOrganismal physiology and survival are influenced by environmental conditions and linked to protein quality control. Proteome integrity is achieved by maintaining an intricate balance between protein folding and degradation. In Caenorhabditis elegans, acute heat stress determines cell non-autonomous regulation of chaperone levels. However, how the perception of environmental changes, including physiological temperature, affects protein degradation remains largely unexplored. Here, we show that loss-of-function of dyf-1 in Caenorhabditis elegans associated with dysfunctional sensory neurons leads to defects in both temperature perception and thermal adaptation of the ubiquitin/proteasome system centered on thermosensory AFD neurons. Impaired perception of moderate temperature changes worsens ubiquitin-dependent proteolysis in intestinal cells. Brain-gut communication regulating protein turnover is mediated by upregulation of the insulin-like peptide INS-5 and inhibition of the calcineurin-regulated forkhead-box transcription factor DAF-16/FOXO. Our data indicate that perception of ambient temperature and its neuronal integration is important for the control of proteome integrity in complex organisms.
Computational studies on defect chemistry and Li-ion conductivity of spinel-type LiAl5O8 as coating material for Li-metal electrode
Authors: Miyakawa Shuntaro , Matsuda Shogo , Tanibata Naoto , Takeda Hayami , Nakayama Masanobu , Saito Takaya , Fukuchi Svetlana 
Published: October 2022

AbstractLi-metal rechargeable batteries are an attractive option for devices that require an extremely high specific energy density, high robustness, and long-term durability, such as high-altitude platform stations. However, Li dendrite growth during charge–discharge cycling causes short-circuit problems. One technical solution is to form an intermediate layer between the Li metal and electrolyte. This interfacial layer should possess mechanical strength, electrochemical stability in the presence of Li, and Li-ion conductivity. In this study, the Li-ion conductivity of spinel-type LiAl5O8 was investigated using first-principles density functional theory and force field molecular dynamics calculations. The calculation results confirmed that stoichiometric LiAl5O8 compounds do not exhibit Li-ion conductivity, whereas off-stoichiometric compounds with excess Li show long-range Li-ion diffusion. The evaluated activation energy was 0.28 eV, which is as low as that of well-known fast Li-ion conductors, such as garnet-type Li7La3Zr2O12. However, the extrapolated Li-ion conductivity at 298 K was relatively low (~ 10−6 S/cm) owing to the limited formation of migration pathways.
Human synovial mesenchymal stem cells show time-dependent morphological changes and increased adhesion to degenerated porcine cartilage
Authors: Tanimoto Takahiro , Endo Kentaro , Sakamaki Yuriko , Ozeki Nobutake , Katano Hisako , Mizuno Mitsuru , Koga Hideyuki , Sekiya Ichiro 
Published: October 2022

AbstractThe possibility that mesenchymal stem cells (MSCs) can adhere to partial defects or degenerative areas in cartilage remains to be established. The purposes of the present study were to verify the adhesion of synovial MSCs to degenerated cartilage, the time course of that adhesion, and the morphological changes that MSCs might undergo during the adhesion process. The surface of pig cartilage was abraded, and a human synovial MSC suspension was placed on the abraded surface. The proportion/number of MSCs that adhered to the cartilage was quantified by counting non-adhered MSCs, measuring the fluorescence intensity of DiI-labeled MSCs, and scanning electron microscopy (SEM) observations. The presence of microspikes or pseudopodia on the MSCs that adhered to the cartilage was also evaluated. SEM confirmed the adhesion of synovial MSCs to degenerated cartilage. The three independent quantification methods confirmed increases in the proportion/number of adhered MSCs within 10 s of placement and over time up to 24 h. The MSCs that adhered at 10 s had a high proportion of microspikes, whereas those that adhered after 1 h had that of pseudopodia. MSCs showed time-dependent morphological changes and increased adhesion to degenerated cartilage after placement of the human synovial MSC suspension.
AHR is a master regulator of diverse pathways in endogenous metabolism
Authors: Granados Jeffry C. , Falah Kian , Koo Imhoi , Morgan Ethan W. , Perdew Gary H. , Patterson Andrew D. , Jamshidi Neema , Nigam Sanjay K. 
Published: October 2022

AbstractThe aryl hydrocarbon receptor (AHR) is a transcription factor with roles in detoxification, development, immune response, chronic kidney disease and other syndromes. It regulates the expression of drug transporters and drug metabolizing enzymes in a proposed Remote Sensing and Signaling Network involved in inter-organ communication via metabolites and signaling molecules. Here, we use integrated omics approaches to analyze its contributions to metabolism across multiple scales from the organ to the organelle. Global metabolomics analysis of Ahr−/− mice revealed the role of AHR in the regulation of 290 metabolites involved in many biochemical pathways affecting fatty acids, bile acids, gut microbiome products, antioxidants, choline derivatives, and uremic toxins. Chemoinformatics analysis suggest that AHR plays a role in determining the hydrophobicity of metabolites and perhaps their transporter-mediated movement into and out of tissues. Of known AHR ligands, indolepropionate was the only significantly altered molecule, and it activated AHR in both human and murine cells. To gain a deeper biological understanding of AHR, we employed genome scale metabolic reconstruction to integrate knockout transcriptomics and metabolomics data, which indicated a role for AHR in regulation of organic acids and redox state. Together, the results indicate a central role of AHR in metabolism and signaling between multiple organs and across multiple scales.
The impact of cell culture media on the interaction of biopolymer-functionalized gold nanoparticles with cells: mechanical and toxicological properties
Authors: Meesaragandla Brahmaiah , Komaragiri Yesaswini , Schlüter Rabea , Otto Oliver , Delcea Mihaela 
Published: October 2022

AbstractUnderstanding the nanoparticle-cell interactions in physiological media is vital in determining the biological fate of the nanoparticles (NPs). These interactions depend on the physicochemical properties of the NPs and their colloidal behavior in cell culture media (CCM). Furthermore, the impact of the bioconjugates made by nanoparticle with proteins from CCM on the mechanical properties of cells upon interaction is unknown. Here, we analyzed the time dependent stability of gold nanoparticles (AuNPs) functionalized with citrate, dextran-10, dextrin and chitosan polymers in protein poor- and protein rich CCM. Further, we implemented the high-throughput technology real-time deformability cytometry (RT-DC) to investigate the impact of AuNP-bioconjugates on the cell mechanics of HL60 suspension cells. We found that dextrin-AuNPs form stable bioconjugates in both CCM and have a little impact on cell mechanics, ROS production and cell viability. In contrast, positively charged chitosan-AuNPs were observed to form spherical and non-spherical aggregated conjugates in both CCM and to induce increased cytotoxicity. Citrate- and dextran-10-AuNPs formed spherical and non-spherical aggregated conjugates in protein rich- and protein poor CCM and induced at short incubation times cell stiffening. We anticipate based on our results that dextrin-AuNPs can be used for therapeutic purposes as they show lower cytotoxicity and insignificant changes in cell physiology.
Optimized parameters for effective SARS-CoV-2 inactivation using UVC-LED at 275 nm
Authors: Lee Cheulkyu , Park Ki Hoon , Kim Minjee , Kim Young Bong 
Published: October 2022

AbstractThe spread of SARS-CoV-2 infections and the severity of the coronavirus disease of 2019 (COVID-19) pandemic have resulted in the rapid development of medications, vaccines, and countermeasures to reduce viral transmission. Although new treatment strategies for preventing SARS-CoV-2 infection are available, viral mutations remain a serious threat to the healthcare community. Hence, medical devices equipped with virus-eradication features are needed to prevent viral transmission. UV-LEDs are gaining popularity in the medical field, utilizing the most germicidal UVC spectrum, which acts through photoproduct formation. Herein, we developed a portable and rechargeable medical device that can disinfect SARS-CoV-2 in less than 10 s by 99.9%, lasting 6 h. Using this device, we investigated the antiviral effect of UVC-LED (275 nm) against SARS-CoV-2 as a function of irradiation distance and exposure time. Irradiation distance of 10–20 cm, < 10 s exposure time, and UV doses of > 10 mJ/cm2 were determined optimal for SARS-CoV-2 elimination (≥ 99.99% viral reduction). The UVC-LED systems have advantages such as fast-stabilizing intensity and insensitivity to temperature, and may contribute to developing medical devices capable of containing SARS-CoV-2 infection. By demonstrating SARS-CoV-2 inactivation with very short-term UVC-LED irradiation, our study may suggest guidelines for securing a safer medical environment.
Effect of electronic reminders on patients’ compliance during clear aligner treatment: an interrupted time series study
Authors: Timm Lan Huong , Farrag Gasser , Wolf Daniel , Baxmann Martin , Schwendicke Falk 
Published: October 2022

AbstractPatient compliance is relevant to achieving therapeutic goals during clear aligner therapy (CAT). The aim of this study was to evaluate the efficacy of remote electronic (e-)reminders and e-feedback on compliance during CAT using an interrupted time series (ITS) analysis. We used routinely collected mobile application data from a German healthtech company (PlusDental, Berlin). Our primary outcome was self-reported compliance (aligner wear time min. 22 h on 75% of their aligners were classified as fully compliant, min. 22 h on 50–74.9% of their aligners: fairly compliant; min. 22 h on < 50% of their aligners: poorly compliant). E-reminders and e-feedback were introduced in the 1st quarter of 2020. Compliance was assessed at semi-monthly intervals from June-December 2019 (n = 1899) and June-December 2020 (n = 5486), resulting in a pre- and post-intervention group. ITS and segmented regression modelling were used to estimate the effect on the change in levels and trends of poor compliance. Pre-intervention, poor compliance was at 24.47% (95% CI: 22.59% to 26.46%). After the introduction of e-reminders and e-feedback (i.e., post-intervention), the percentage of poorly compliant patients decreased substantially, levelling off at 9.32% (95% CI: 8.31% to 10.45%). E-reminders and e-feedback were effective for increasing compliance in CAT patients.Clinical Significance: Orthodontists and dentists may consider digital monitoring and e-reminders to improve compliance and increase treatment success.
Efficacy of ultrasound endoscopy with artificial intelligence for the differential diagnosis of non-gastric gastrointestinal stromal tumors
Authors: Minoda Yosuke , Ihara Eikichi , Fujimori Nao , Nagatomo Shuzaburo , Esaki Mitsuru , Hata Yoshitaka , Bai Xiaopeng , Tanaka Yoshimasa , Ogino Haruei , Chinen Takatoshi , Hu Qingjiang , Oki Eiji , Yamamoto Hidetaka , Ogawa Yoshihiro 
Published: October 2022

AbstractGastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.
Rotating magnetocaloric effect in highly anisotropic TbIII and DyIII single molecular magnets
Authors: Konieczny Piotr , Czernia Dominik , Kajiwara Takashi 
Published: October 2022

AbstractThe magnetocaloric effect (MCE) was investigated in highly anisotropic single crystals of two single molecule magnets (SMMs): [LnIII(ZnIIL)2]CF3SO3, where Ln = Tb, Dy and L = tripodal hexadentate Schiff base ligand. The structure of these paramagnetic compounds consists of identically oriented linear trinuclear clusters in a trigonal system with an easy direction c∥Zn–Ln–Zn array and a hard plane ab⊥Zn–Ln–Zn array. The magnitude of MCE measured for c∥H was significantly greater than MCE for ab∥H at a wide temperature range regardless of the studied SMM. Therefore, the rotating magnetocaloric effect (RMCE) was evaluated. The maxima of the magnetic entropy change for RMCE were obtained at 2.0 K and moderate fields: 3.9 J K−1 kg−1 at µ0H = 1.3 T for Ln = Tb and 3.3 J K−1 kg−1 at µ0H = 1.1 T for Ln = Dy. The relative efficiency of RMCE compared to the MCE measured in c∥H was as high as 99% at low magnetic fields.
Evaluation of the relative potential for contact and doffing transmission of SARS-CoV-2 by a range of personal protective equipment materials
Authors: Xue Xuan , Coleman Christopher M. , Duncan Joshua D. , Hook Andrew L. , Ball Jonathan K. , Alexander Cameron , Alexander Morgan R. 
Published: October 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the causative agent of coronavirus disease 2019 (COVID-19)—has caused a global public health emergency. Personal protective equipment (PPE) is the primary defence against viral exposure in healthcare and community settings. However, the surfaces of PPE materials may trap virus for contact transmission or through laden aerosols generated during removal of PPE, through cleaning or during movement. In this study, the relative efficacy of current PPE materials in terms of virion adsorption to materials and their antiviral potency, has been evaluated on a wide range of PPE for the first time, including four polymer glove types, two types of scrubs, apron material, a mask, visor and a selection of other commercial polymers and products. Although differences in virion adsorption to the test materials were observed, none of the existing polymer-based PPE resulted in more than tenfold reduction in the SARS-CoV-2 titre within either 10 min or 30 min contact period. The wettability and surface chemistry of the test materials were analysed to investigate any correlations with their surface physicochemical properties. While no correlation was found between wettability and viral retention under air flow challenge, one secondary ion of m/z 101.03 (+) and three secondary ions of m/z 31.98 (−), 196.93 (−) and 394.33 (+) in ToF–SIMS data of the test materials showed positive and negative correlations with the viral retention, respectively, which was identified by PLS regression model, suggesting that the surface chemistry plays a role in determining the extent of virion adsorption. Our findings outline the material aspects that influence the efficacy of current PPE against SARS-CoV-2 transmission and give suggestions on the development of novel simple polymer-based PPE for better infection protection.