bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and structure-based drug design of cell-active inhibitors of interleukin 17A at a novel C-terminal site
Authors: Goedken Eric R. , Argiriadi Maria A. , Dietrich Justin D. , Petros Andrew M. , Krishnan Navasona , Panchal Sanjay C. , Qiu Wei , Wu Haihong , Zhu Haizhong , Adams Ashley M. , Bodelle Pierre M. , Goguen Lucas , Richardson Paul L. , Slivka Peter F. , Srikumaran Myron , Upadhyay Anup K. , Wu Bainan , Judge Russell A. , Vasudevan Anil , Gopalakrishnan Sujatha M. , Cox Philip B. , Stoll Vincent S. , Sun Chaohong 
Published: August 2022

AbstractAnti-IL17A therapies have proven effective for numerous inflammatory diseases including psoriasis, axial spondylitis and psoriatic arthritis. Modulating and/or antagonizing protein–protein interactions of IL17A cytokine binding to its cell surface receptors with oral therapies offers the promise to bring forward biologics-like efficacy in a pill to patients. We used an NMR-based fragment screen of recombinant IL17A to uncover starting points for small molecule IL17A antagonist discovery. By examining chemical shift perturbations in 2D [1H,13C-HSQC] spectra of isotopically labeled IL17A, we discovered fragments binding the cytokine at a previously undescribed site near the IL17A C-terminal region, albeit with weak affinity (> 250 µM). Importantly this binding location was distinct from previously known chemical matter modulating cytokine responses. Subsequently through analog screening, we identified related compounds that bound symmetrically in this novel site with two copies. From this observation we employed a linking strategy via structure-based drug design and obtained compounds with increased binding affinity (< 50 nM) and showed functional inhibition of IL17A-induced cellular signaling (IC50~1 µM). We also describe a fluorescence-based probe molecule suitable to discern/screen for additional molecules binding in this C-terminal site.
Effects of lymphocyte and neutrophil counts and their time courses on mortality in patients with postoperative pneumonia
Authors: Murakami Yasushi , Shindo Yuichiro , Sano Masahiro , Okumura Junya , Kobayashi Hironori , Sakakibara Toshihiro , Iguchi Mitsutaka , Takahashi Kunihiko , Yagi Tetsuya , Matsui Shigeyuki , Hasegawa Yoshinori 
Published: August 2022

AbstractThe prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC < 500 cells/μL) at diagnosis was associated with worse 90-day survival in both types of pneumonia. In POP patients, neutrophilia (ANC > 7500 cells/μL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.
Ophthalmic viscosurgical device interaction with two hydrophobic acrylic intraocular lenses of different equilibrium water content
Authors: Auffarth Gerd U. , Schickhardt Sonja K. , Fang Hui , Wang Qiang , Khoramnia Ramin , Yildirim Timur M. 
Published: August 2022

AbstractOphthalmic viscosurgical device (OVD) is used during intraocular surgery to protect ocular tissue. It requires complete removal from the eye by the end of surgery to avoid postoperative complications. This study compares the interaction of a cohesive OVD with two different intraocular lenses (IOLs) of different equilibrium water content. In this laboratory study on porcine cadaver eyes, the capsular bags and anterior chambers of each eye were filled with fluorescein-stained OVD. Following implantation of 10 IOLs each of Clareon CNA0T0 and AcrySof SN60WF (Alcon Laboratory, Fort Worth, USA) IOLs, the OVD was removed using the irrigation/aspiration mode. The OVD removal was timed and differences between the both IOL groups were compared. OVD removal time ranged from 18 to 40 s (mean ± SD, 26.4 ± 6.8 s) and from 16 to 39 s (mean ± SD, 23.6 ± 6.6 s) for eyes implanted with a CNA0T0 and a SN60WF IOL, respectively, without a statistically significant difference between the groups, P > 0.05. Cohesive OVD removal times were similar between the CNA0T0 and SN60WF groups. Surgeons should experience no differences regarding the interaction between cohesive OVDs and IOLs made from the new Clareon material compared to the established AcrySof material.
Reduction of lithium induced interstitial fibrosis on co-administration with amiloride
Authors: Mehta Paulomi M. , Gimenez Gregory , Walker Robert J. , Slatter Tania L. 
Published: August 2022

AbstractLong-term administration of lithium is associated with chronic interstitial fibrosis that is partially reduced with exposure to amiloride. We examined potential pathways of how amiloride may reduce interstitial fibrosis. Amiloride was administered to a rat model of lithium induced interstitial fibrosis over a long term (6 months), as well as for short terms of 14 and 28 days. Kidney cortical tissue was subjected to RNA sequencing and microRNA expression analysis. Gene expression changes of interest were confirmed using immunohistochemistry on kidney tissue. Pathways identified by RNA sequencing of kidney tissue were related to ‘promoting inflammation’ for lithium and ‘reducing inflammation’ for amiloride. Validation of candidate genes found amiloride reduced inflammatory components induced by lithium including NF-κB/p65Ser536 and activated pAKTSer473, and increased p53 mediated regulatory function through increased p21 in damaged tubular epithelial cells. Amiloride also reduced the amount of Notch1 positive PDGFrβ pericytes and infiltrating CD3 cells in the interstitium. Thus, amiloride attenuates a multitude of pro-inflammatory components induced by lithium. This suggests amiloride could be repurposed as a possible anti-inflammatory, anti-fibrotic agent to prevent or reduce the development of chronic interstitial fibrosis.
The association between dietary sodium intake and osteoporosis
Authors: Hong Susie , Choi Jong Wook , Park Joon-Sung , Lee Chang Hwa 
Published: August 2022

AbstractThe association of inadequate dietary sodium intake with bone mineral density (BMD) and the risk of osteoporosis is controversial. To find the association between low sodium diet and the risk of incipient osteoporosis, we performed a population-based cross-sectional analysis using Tanaka method for estimation 24-h urinary sodium excretion (e24hUNaETanaka) as a candidate indicator of sodium intake. We identified 3869 participants without osteoporosis and classified them into quartiles according to their value of e24hUNaETanaka. BMD was measured to find participants at risk of osteoporosis. Lower e24hUNaETanakawas related to decreasing BMD of the distal radius. Multiple Cox-proportional hazard models demonstrated that e24hUNaETanakahad an inverse association with the risk of osteoporosis (adjusted HR = 0.859, 95% CI = 0.751–0.982) and survival analysis revealed that the lowest quartile group had poor osteoporosis-free survival (PLog-rank < 0.0001). Furthermore, our restricted cubic spline analysis revealed that the relationship between e24hUNaETanakaand HR of osteoporosis was negative curvilinear in males and postmenopausal females and positive linear in premenopausal females. Our findings suggest that lower sodium intake was a significant predictor of incipient osteoporosis and there was wide variation in this relationship according to sex and female hormone status.
Cognitive performance, creativity and stress levels of neurotypical young adults under different white noise levels
Authors: Awada Mohamad , Becerik-Gerber Burcin , Lucas Gale , Roll Shawn 
Published: August 2022

AbstractNoise is often considered a distractor; however recent studies suggest that sub-attentive individuals or individuals diagnosed with attention deficit hyperactivity disorder can benefit from white noise to enhance their cognitive performance. Research regarding the effect of white noise on neurotypical adults presents mixed results, thus the implications of white noise on the neurotypical population remain unclear. Thus, this study investigates the effect of 2 white noise conditions, white noise level at 45 dB and white noise level at 65 dB, on the cognitive performance, creativity, and stress levels of neurotypical young adults in a private office space. These conditions are compared to a baseline condition where participants are exposed to the office ambient noise. Our findings showed that the white noise level at 45 dB resulted in better cognitive performance in terms of sustained attention, accuracy, and speed of performance as well as enhanced creativity and lower stress levels. On the other hand, the 65 dB white noise condition led to improved working memory but higher stress levels, which leads to the conclusion that different tasks might require different noise levels for optimal performance. These results lay the foundation for the integration of white noise into office workspaces as a tool to enhance office workers’ performance.
Remote synchronous usability testing of public access defibrillators during social distancing in a pandemic
Authors: Currie Hannah , Harvey Adam , Bond Raymond , Magee Justin , Finlay Dewar 
Published: August 2022

AbstractPublic access automated external defibrillators (AEDs) represent emergency medical devices that may be used by untrained lay-persons in a life-critical event. As such their usability must be confirmed through simulation testing. In 2020 the novel coronavirus caused a global pandemic. In order to reduce the spread of the virus, many restrictions such as social distancing and travel bans were enforced. Usability testing of AEDs is typically conducted in-person, but due to these restrictions, other usability solutions must be investigated. Two studies were conducted, each with 18 participants: (1) an in-person usability study of an AED conducted in an office space, and (2) a synchronous remote usability study of the same AED conducted using video conferencing software. Key metrics associated with AED use, such as time to turn on, time to place pads and time to deliver a shock, were assessed in both studies. There was no difference in time taken to turn the AED on in the in-person study compared to the remote study, but the time to place electrode pads and to deliver a shock were significantly lower in the in-person study than in the remote study. Overall, the results of this study indicate that remote user testing of public access defibrillators may be appropriate in formative usability studies for determining understanding of the user interface.
PERM1 regulates genes involved in fatty acid metabolism in the heart by interacting with PPARα and PGC-1α
Authors: Huang Chun-yang , Oka Shin-ichi , Xu Xiaoyong , Chen Chian-Feng , Tung Chien-Yi , Chang Ya-Yuan , Mourad Youssef , Vehra Omair , Ivessa Andreas , Yehia Ghassan , Romanienko Peter , Hsu Chiao-Po , Sadoshima Junichi 
Published: August 2022

AbstractPERM1 (PGC-1/ERR-induced regulator in muscle 1) is a muscle-specific protein induced by PGC-1 and ERRs. Previous studies have shown that PERM1 promotes mitochondrial biogenesis and metabolism in cardiomyocytes in vitro. However, the role of endogenous PERM1 in the heart remains to be investigated with loss-of-function studies in vivo. We report the generation and characterization of systemic Perm1 knockout (KO) mice. The baseline cardiac phenotype of the homozygous Perm1 KO mice appeared normal. However, RNA-sequencing and unbiased pathway analyses showed that homozygous downregulation of PERM1 leads to downregulation of genes involved in fatty acid and carbohydrate metabolism in the heart. Transcription factor binding site analyses suggested that PPARα and PGC-1α are involved in changes in the gene expression profile. Chromatin immunoprecipitation assays showed that PERM1 interacts with the proximal regions of PPAR response elements (PPREs) in endogenous promoters of genes involved in fatty acid oxidation. Co-immunoprecipitation and reporter gene assays showed that PERM1 promoted transcription via the PPRE, partly in a PPARα and PGC-1α dependent manner. These results suggest that endogenous PERM1 is involved in the transcription of genes involved in fatty acid oxidation through physical interaction with PPARα and PGC-1α in the heart in vivo.
Seasonal variation in wing size and shape of Drosophila melanogaster reveals rapid adaptation to environmental changes
Authors: Önder Banu Şebnem , Aksoy Cansu Fidan 
Published: August 2022

AbstractPopulations in seasonal fluctuating environments receive multiple environmental cues and must deal with this heterogenic environment to survive and reproduce. An enlarged literature shows that this situation can be resolved through rapid adaptation inDrosophila melanogasterpopulations. Long-term monitoring of a population in its natural habitat and quantitative measurement of its responses to seasonal environmental changes are important for understanding the adaptive response ofD. melanogasterto temporal variable selection. Here, we use inbred lines of aD. melanogasterpopulation collected at monthly intervals between May to October over a temporal scale spanning three consecutive years to understand the variation in wing size and wing shape over these timepoints. The wing size and shape of this population changed significantly between months and a seasonal cycle of this traits is repeated for three years. Our results suggest that the effects of environmental variables that generated variation in body size between populations such as latitudinal clines, are a selective pressure in a different manner in terms of seasonal variation. Temperature related variable have a significant nonlinear relation to this fluctuating pattern in size and shape, whereas precipitation and humidity have a sex-specific effect which is more significant in males.
Exploring the mechanistic link between SF3B1 mutation and ring sideroblast formation in myelodysplastic syndrome
Authors: Ochi Tetsuro , Fujiwara Tohru , Ono Koya , Suzuki Chie , Nikaido Maika , Inoue Daichi , Kato Hiroki , Onodera Koichi , Ichikawa Satoshi , Fukuhara Noriko , Onishi Yasushi , Yokoyama Hisayuki , Nakamura Yukio , Harigae Hideo 
Published: August 2022

AbstractAcquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1K700E. SF3B1K700E expressing cells showed higher proportion of RS than the control cells along with erythroid differentiation, indicating the direct contribution of mutant SF3B1 expression in erythroblasts to RS formation. In SF3B1K700E expressing cells, ABCB7 and ALAS2, known causative genes for congenital sideroblastic anemia, were downregulated. Additionally, mis-splicing of ABCB7 was observed in SF3B1K700E expressing cells. ABCB7-knockdown HUDEP-2 cells revealed an increased frequency of RS formation along with erythroid differentiation, demonstrating the direct molecular link between ABCB7 defects and RS formation. ALAS2 protein levels were obviously decreased in ABCB7-knockdown cells, indicating decreased ALAS2 translation owing to impaired Fe–S cluster export by ABCB7 defects. Finally, RNA-seq analysis of MDS clinical samples demonstrated decreased expression of ABCB7 by the SF3B1 mutation. Our findings contribute to the elucidation of the complex mechanisms of RS formation in MDS-RS.
A chromosome-level genome assembly provides insights into the environmental adaptability and outbreaks of Chlorops oryzae
Authors: Zhou Ailin , Huang Cong , Li Yi , Li Xinwen , Zhang Zhengbing , He Hualiang , Ding Wenbing , Xue Jin , Li Youzhi , Qiu Lin 
Published: August 2022

AbstractChlorops oryzae is a pest of rice that has caused severe damage to crops in major rice-growing areas in recent years. We generated a 447.60 Mb high-quality chromosome-level genome with contig and scaffold N50 values of 1.17 Mb and 117.57 Mb, respectively. Hi-C analysis anchored 93.22% scaffolds to 4 chromosomes. The relatively high expression level of Heat Shock Proteins (HSPs) and antioxidant genes in response to thermal stress suggests these genes may play a role in the environmental adaptability of C. oryzae. The identification of multiple pathways that regulate reproductive development (juvenile hormone, 20-hydroxyecdsone, and insulin signaling pathways) provides evidence that these pathways also play an important role in vitellogenesis and thus insect population maintenance. These findings identify possible reasons for the increased frequency of outbreaks of C. oryzae in recent years. Our chromosome-level genome assembly may provide a basis for further genetic studies of C. oryzae, and promote the development of novel, sustainable strategies to control this pest.
LED-pump-X-ray-multiprobe crystallography for sub-second timescales
Authors: Hatcher Lauren E. , Warren Mark R. , Skelton Jonathan M. , Pallipurath Anuradha R. , Saunders Lucy K. , Allan David R. , Hathaway Paul , Crevatin Giulio , Omar David , Williams Ben H. , Coulson Ben A. , Wilson Chick C. , Raithby Paul R. 
Published: August 2022

AbstractThe visualization of chemical processes that occur in the solid-state is key to the design of new functional materials. One of the challenges in these studies is to monitor the processes across a range of timescales in real-time. Here, we present a pump-multiprobe single-crystal X-ray diffraction (SCXRD) technique for studying photoexcited solid-state species with millisecond-to-minute lifetimes. We excite using pulsed LEDs and synchronise to a gated X-ray detector to collect 3D structures with sub-second time resolution while maximising photo-conversion and minimising beam damage. Our implementation provides complete control of the pump-multiprobe sequencing and can access a range of timescales using the same setup. Using LEDs allows variation of the intensity and pulse width and ensures uniform illumination of the crystal, spreading the energy load in time and space. We demonstrate our method by studying the variable-temperature kinetics of photo-activated linkage isomerism in [Pd(Bu4dien)(NO2)][BPh4] single-crystals. We further show that our method extends to following indicative Bragg reflections with a continuous readout Timepix3 detector chip. Our approach is applicable to a range of physical and biological processes that occur on millisecond and slower timescales, which cannot be studied using existing techniques.
Future growth and decline of high mountain Asia's ice-dammed lakes and associated risk
Authors: Compagno Loris , Huss Matthias , Zekollari Harry , Miles Evan S. , Farinotti Daniel 
Published: August 2022

AbstractGlaciers around the world are shrinking rapidly and will continue to do so in the next decades. Anticipating the consequences resulting from such glacier changes is key to design and implement adequate mitigation measures. Here, we focus on the future evolution of potential ice-dammed and supraglacial lakes in High Mountain Asia, as such lakes are responsible for the majority of glacier lake outburst floods in the region. We identify 11,129 potential lakes at present, with a total maximum volume of 2070 million m3. We find a strong correlation between large modelled lakes and historical outburst floods. By accounting for the evolution of glaciers under different climate change mitigation measures, we project that the number of potential ice-dammed lakes could increase by between 15 and 18% until 2080, with a concomitant 45–55% increase in their volume. Our findings thus suggest that a temporary increase of glacier lake outburst floods is to be expected in the coming decades.
Krankenhausgewinne – Ethische Aspekte an der Schnittstelle
zwischen Medizin und Ökonomie
Authors: Kapitza Thomas 
Published: August 2022

ZusammenfassungKrankenhausgewinne und Ökonomisierungstendenzen rücken zunehmend
in den Mittelpunkt der Diskussion um die Verbesserung des Gesundheitswesens.
Gewinnorientierte Ansätze zur Erzielung von Krankenhausrenditen haben
eine ethische Dimension, denn das Patientenwohl muss im Vordergrund bleiben. Ein
bedarfsorientierter wirtschaftlicher Ansatz ohne die Dominanz primärer
Gewinnziele sollte zum übergreifenden Rahmen für den
Krankenhaussektor werden.
Reduction of Severe Hypoglycemic Events Among Outpatients with Type 2
Diabetes Following Sodium-Glucose Cotransporter 2 Inhibitor Marketing in
Japan
Authors: Yamashita Koh , Yoshiike Shouichi , Yamashita Taku , Mori Jun-ichirou , Aizawa Toru 
Published: August 2022

AbstractRecently, oral hypoglycemic agents with newer glucose lowering mechanisms have
been on release. This is mostly to meet the diabetic patient’s need to
avoid hypoglycemia, which is profoundly important for better long-term outcome
of the treatment. In this study, we quantified the annual number of patients
with type 2 diabetes who experienced hypoglycemia needing the third-party
assistance who had random sample plasma
glucose<59.4 mg/dl (3.3 mmol/l) on the
one hand and analyzed the prescription trend of hypoglycemic agents all over
Japan on the other. Analysis of the annual number of hypoglycemic patients
visited ER was performed at Aizawa Hospital, a medical center located in the
midst of a city. The study duration was over 10 years from 2008 to 2019. We
found a clear-cut decreasing trend of hypoglycemia over the 10 years, ca.
61/year to 39/year. Immediately after the release of
sodium-glucose co-transporter-2 inhibitors, since 2013 to 2017, the decrease was
rather sharp as 81/year to 31/year, and the change of the
national number of its prescription inversely correlated with the change of the
number of the patients with hypoglycemia. This was not the case immediately
after the introduction of dipeptidyl peptidase-4 inhibitors in the Japanese
market since 2008 to 2012. There was no significant correlation between its
prescription and the number of patients with hypoglycemia. The data strongly
suggested that there was a causal relationship exclusively between the
introduction of sodium-glucose cotransporter-2 inhibitor, and the reduction of
hypoglycemic events among patients with type 2 diabetes.
Role of Whole-Body Computed Tomography Scan to Avoid Missed Foreign Body in Patients with Multiple Stab Injury: A Rare Case of Retained Impaled Knife Blade with Intact Neurology
Authors: Hajare Swapnil , Shetty Ajoy , Ramachandran Karthik , Shanmuganathan Rajasekaran 
Published: August 2022

AbstractNonmissile penetrating spine injury (NMPSI) is usually encountered in young men, secondary to knife-inflicted injuries. Such injuries often present with complete or incomplete neurodeficit. We hereby report a case of NMPSI (due to impaled knife blade) in the cervical spine, who presented with intact neurology. She was managed by foreign body removal, dural repair, and cerebrospinal fluid (CSF) diversion with lumbar drain. We performed postoperative magnetic resonance imaging with diffusion tensor imaging and tractography to ascertain the cord status. The case highlights the importance of whole-body computed tomography in patients with multiple stab wounds and the use of CSF diversion in such situations.