bluuebunny/crossref_metadata_2025 huggingface dataset:
A concise analytical model for the ideal reverse osmosis desalination processes
Authors: Song Lianfa
Published: October 2023

Permeate recovery is a key parameter that plays a central role in the performance assessment and optimization of reverse osmosis processes. It remains a great challenge for engineers in the field to determine the recovery conveniently and accurately from the basic parameters of a membrane system. A concise analytical model is presented here that, without the need for the empirical or fitting coefficients and tedious numerical calculation, links the recovery of a reverse osmosis process rigorously to three basic parameters: the feed water salt concentration, the characteristic of membrane process, and the driving pressure. A graphical solution method to the model is also introduced to find out the recovery effortlessly. The concise model and graphical method are demonstrated under various conditions as a powerful tool for the performance simulations and improvement of reverse osmosis processes.

Practitioner Points

A concise model is presented for permeate recovery in an ideal RO desalination system.

The recovery of an RO system is analytically related to a few system parameters.

A graphical solution method is introduced to find out the explicit recovery.

The ideal RO model can be a powerful tool for simulation of RO processes.
Factors associated with early discontinuation of anamorelin in patients with cancer-associated cachexia
Authors: Tsukiyama Ikuto , Iwata Takashi , Takeuchi Tomoko , Kato Ryoko Inuzuka , Sakuma Masaki , Tsukiyama Sumiyo , Kato Mana , Ikeda Yoshiaki , Ohashi Wataru , Kubo Akihito , Mori Naoharu
Published: October 2023

Purpose

Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, is an unremitting problem for cancer patients. Anamorelin has become available for cancer-associated cachexia, but early discontinuation is common in clinical practice. This study aimed to explore factors related to the early discontinuation of anamorelin and its relationship to survival.

Patients and methods

This prospective, observational study of multimodal clinical practice involved patients who took anamorelin (100 mg) for cancer-associated cachexia at Aichi Medical University Hospital between 14 May 2021 and 31 March 2022. In July 2022, clinical data were extracted from electronic clinical records. Patients who discontinued anamorelin less than 4 weeks after initiation were defined as the early discontinuation group, and their clinical data and survival time were compared with those of the continuation group. This study was approved by the Ethics Committee of the university (approval no. 2021-124).

Results

Of the 42 patients treated with anamorelin, 40 (median age 72.5 years, median BMI 18.7 kg/m2) were analyzed, including 13 with non-small cell lung cancer, and 12 with pancreatic, 8 with colorectal, and 7 with gastric cancers. On univariate analysis, the early discontinuation group included more patients with worse performance status (PS) (p=0.028), low prognostic nutritional index (PNI) (p=0.001), and no concomitant anticancer drugs (p=0.003). On multivariate analysis, PS and PNI were related to anamorelin continuation. Survival time was significantly shorter in the early discontinuation group (p=0.039).

Conclusion

Worse PS and low PNI were associated with early discontinuation of anamorelin. Longer survival time was observed in the continuation group.
Percutaneous Coronary Interventions in Women
Authors: Joodi Golsa , Palimar Sristi , Press Marcella Calfon
Published: October 2023

Purposeof Review

Cardiovascular disease is the leading cause of morbidity and mortality among women globally. Numerous studies show ongoing disparities in diagnosis, management, and outcomes of ischemic heart disease in women compared to men. We aim to review the factors contributing to sex-based differential outcomes of percutaneous coronary interventions in women.

Recent Findings

Hormonal influence on coronary arteries and progression of atherosclerosis in women results in distinct coronary plaque characteristics and unique pathological process such as spontaneous coronary artery dissection and myocardial infarction with non-obstructive coronary arteries. During the presentation of acute coronary syndromes, women are older and have higher burden of comorbidities, with higher short- and long-term mortality.

Awareness of differences in vascular biology and unique risk factors for cardiovascular disease in women is essential for sustained improvement in cardiovascular mortality. Better representation of women in trials is crucial to address the gaps in knowledge and allow for individualized treatment approaches in women.
Application of an innovative pancreaticojejunostomy technique with a modified set of perioperative management in pancreatoduodenectomy: a retrospective cohort study
Authors: Chen Shiyin , Zhang Cheng , Huang Haifeng , Xi Bin , Zhang Jian , Jin Yibing , Gao Shunliang , Zhang Yun
Published: October 2023

How to reduce grade C postoperative pancreatic fistula (POPF) incidence after pancreaticoduodenectomy (PD) is the pursuit of pancreatic surgeons. This study introduced an innovative pancreaticojejunostomy (PJ) technique with a complete set of perioperative management. All 144 patients in this single-center retrospective cohort study underwent the same PJ technique and perioperative management. The primary endpoint was grade C POPF incidence. The secondary endpoints were grade B POPF rate, drain fluid amylase level, complications, hospital stay duration, and mortality. Risk factors for clinically-relevant POPF (CR-POPF) were assessed by logistic regression analysis. No patient (0.0%) experienced grade C POPF, while 44 (30.6%) developed grade B. No in-hospital death was recorded. Multivariate analysis found relatively high body mass index, laparoscopic surgery, and soft or moderate pancreatic texture independent risk factors for CR-POPF. Our novel PJ anastomosis with modified perioperative management helped avoid grade C POPF. However, grade B POPF incidence was relatively high to some extent because of the enhanced management itself.
Semipermeable Handschuhe in der Prävention berufsbedingter Hauterkrankungen:
Authors: Heichel T. , Sonsmann F. K. , John S. M. , Nienhaus A. , Nordheider K. , Wilke A. , Brans R.
Published: October 2023

Bereits seit vielen Jahren werden textile Handschuhe als Komfort- oder Unterziehhandschuhe in der Prävention von Berufsdermatosen eingesetzt, z. B. zur Abmilderung von Okklusionseffekten beim Tragen flüssigkeitsdichter Schutzhandschuhe oder zur Unterstützung der Externatherapie. In den letzten Jahren wurden Handschuhe aus semipermeablen Membranen bzw. Laminaten entwickelt, die zukünftig einen weiteren Baustein in der Versorgung beruflich bedingter Hauterkrankungen darstellen können. Diese zeigen sowohl in experimentellen/hautphysiologischen Untersuchungen als auch in berufspraktischen/realitätsnahen Anwenderstudien eine gute Hautverträglichkeit, Wirksamkeit und berufsgruppenübergreifende Akzeptanz in der Anwendung als Komfort- oder Unterziehhandschuhe. Je nach berufsspezifischem Anforderungsprofil (z. B. Einsatzbereich, Tragedauer der Schutzhandschuhe, Anforderung an die Feinmotorik) sowie individuellen Präferenzen (z. B. Passform, Optik, Praktikabilität) könnten semipermeable Handschuhe zukünftig eine gute Alternative gegenüber den bisher eingesetzten textilen Handschuhen darstellen und dadurch zur Erweiterung und Optimierung aktuell bestehender Therapie- und Schutzmaßnahmen in der Prävention berufsbedingter Hauterkrankungen beitragen.
Why Do You Make Things So Complicated? Understanding the Texts of Regulations During the COVID-19 Pandemic
Authors: Alfano Vincenzo , Guarino Massimo
Published: October 2023

The last two years have been characterized by a considerable increase in the number of national and local regulations to contain and fight the spread of the COVID-19 contagion. The literature suggests that poor readability of regulations comes with a significant cost in terms of public compliance, in various contexts. Does the readability of COVID-19 regulations impact their effectiveness? We study the matter in Italy, a country severely affected by the first wave of COVID-19, and one that has seen many local regulations that have tried to halt the virus. Our empirical evidence, obtained from a corpus built on the basis of all 640 regional COVID-19 regulations that have been published, was collected from the Italian Conference of Regions and Autonomous Provinces between 21 February and 14 June 2020. Our results, obtained through F-GLS estimations with fixed, hybrid, and random effects, suggest that the readability of the regulations affected the spread of the pandemic, and that an improvement in readability would lead to more efficient outcomes.
Nickel sulfate solution fluoride separation with hydrous zirconium oxide
Authors: Nigri Elbert M. , Sultana Ummul K. , Santos André L. A. , Vaughan James W. , Rocha Sônia D. F.
Published: October 2023

Fluoride is an impurity in nickel sulfate production, which is required for electric vehicle batteries. Hydrous zirconium oxide (HZO) was evaluated for removing fluoride from nickel sulfate solution. Maximum fluoride removal occurred at pH value 4 and optimal pH value is 4–5, considering Zr solubility. Fluoride availability decreases with pH due to hydrogen fluoride and zirconium fluoride aqueous species. Fluoride removal is initially rapid, with 50 wt.% removal in 7 min, followed by slow removal up to 68 wt.% after 72 h and follows second order rate kinetics. Fluoride removal was dominated by an ion exchange mechanism and resulting Zr–F bonds were observed using Fourier-transform infrared spectroscopy. The presence of nickel sulfate decreased loading capacity compared to a salt-free solution. HZO maintained adsorption capacity through five cycles of loading and regeneration.
Roundtable discussion: rethinking and exploring smart city development
Authors: Wu Siegfried Zhiqiang , Zhen Feng , Wu Xiaoli , Guo Leixian , Zhou Xingang , Zhao Ying , Mao Weiying , Hu Jingjing , Liu Zhaohui
Published: October 2023

Since the concept of the "Smart City" was proposed in 2008, the construction of smart cities has developed rapidly. While embracing smart cities, we are also gradually realizing that creating good cities cannot rely solely on new technologies. The wisdom of cities is profound and should be noted that the essence of a smart city is the intelligentization of urban entities, including the government, enterprises, and citizens. The construction of a smart city must be combined with the needs of the government, enterprises, and citizens. Especially for the iteration of smart city construction, government guidance is the key to the development of smart city construction. Enterprises are active responders and promoters of smart city construction, and users are evaluators of the achievements of smart city construction. Against this backdrop, this salon, based on more than a decade of exploration, has launched discussions around "Smart City: Reflecting on the Gains and Losses of Exploration", inviting experts from different industries such as universities, research institutes, and enterprises to exchange and speculate, discussing the difficulties and challenges faced by smart cities, as well as the development trends of new smart cities in the future. The construction focus of smart cities and how to achieve the vision of "cities make life better" are also discussed, in order to provide ideas for the future development of smart cities.
Reynolds number dependence of azimuthal and streamwise pipe flow structures
Authors: Zanoun E.-S. , Dewidar Y. , Egbers C.
Published: October 2023

This paper revisits the study by Baileyet al.(J. Fluid Mech., vol. 615, 2008, pp. 121–138), adopting a higher-fidelity calibration approach to reveal subtle flow variations with Reynolds numbers that were not discernible previously. The paper aims therefore to provide insights into the characteristics of azimuthal and streamwise pipe flow structures adopting two-point joint statistics and spectral analysis for shear Reynolds numbers in the range$2\times {10^3}\le {Re_\tau }\le {16\times {10^3}}$, where${Re_\tau }$is based on the wall friction velocity$u_{\tau }$, the pipe radius$R$, and the fluid kinematic viscosity$\nu$. The streamwise velocity fluctuations were measured at four wall-normal locations,$0.1\le {x_{{2}}/R}\le {0.7}$, covering the logarithmic and core regions of fully developed turbulent pipe flow based on 35–41 azimuthal probe separations using, simultaneously, two single hot-wire probes. A uniquein situcalibration approach for both probes was adopted where a potential flow was insured, resulting in consistent and precise pipe flow data. The azimuthal velocity correlation, the cross-power spectral density and the coherence function of the streamwise velocity fluctuations are discussed, revealing a clear dependence of the azimuthal scales of the large and very large flow motions on the wall-normal location, the azimuthal separation, the streamwise wavenumber and the Reynolds number. Along the logarithmic region, a linear growth of the azimuthal scales of the large- and very-large-scale structures was observed; however, they do scale nonlinearly and reach their maximum sizes in the core region, i.e. near the centreline of the pipe. Additionally, the streamwise very-large- and large-scale motions were evaluated using the premultiplied energy spectra, showing wavelengths${\approx }{18R}$and${\approx }{3R}$for${Re_{\tau }}\approx {16\times {10^3}}$at half of the pipe radius, respectively.
Protection of LGBTQIA+ rights in armed conflict: How (and whether) to ‘queer’ the crime against humanity of persecution in international criminal law?
Authors: Peretko Aneta
Published: October 2023

The discrimination faced every day by LGBTQIA+ individuals does not disappear during armed conflict. On the contrary, such persons have been, and continue to be, targeted for particularly heinous human rights violations due to their sexual orientation and/or gender identity. And while international human rights law has, in the last two decades, made significant leaps in prohibiting discrimination on these grounds, international criminal law lags behind. The Rome Statute of the International Criminal Court only criminalizes persecution, an extreme form of discrimination, on grounds of gender and other grounds universally recognized in international law rather than on grounds of sexual orientation or gender identity. In the absence of clear textual criminalization of queer persecution, this article argues international law can be queerly reinterpreted to fit sexual orientation and gender identity into the confines of ‘gender’. However, while acknowledging the normative and expressive gains that could come from using international criminal law to pursue queer persecution, this article also notes the costs, including the flattening of queer discrimination into the narrow rubric of gender and suppressing its more radical principles. Therefore, while concluding international criminal law can be queerly reinterpreted, this article expresses doubts as to whether, in fact, it should.
The clinical significance of ischaemia-modified albumin in acute coronary syndrome and hypertension
Authors: Pan Guoyan , Chen Jinzao , Lv Congying , Lin Xueping , Huang Junwei , Lin Bin , Wu Zhiwei
Published: October 2023

Background:

Early diagnosis of acute coronary syndrome is more and more important because of its mortality and morbidity. Hypertension is one of the pathogenesis of acute coronary syndrome, which often leads to stenosis and ischaemia. Ischaemia-modified albumin is sensitive for the occurrence of ischaemia, which attracted us in the significance of ischaemia-modified albumin in patients with chest pain, especially patients complicated with hypertension.

Methods:

In total, 200 patients with acute chest pain were included in the study. According to the diagnostic criteria, patients were divided into acute coronary syndrome group and non-ischaemic chest pain group. Cardiac biomarkers were measured with 30 minutes in emergency department, including cardiac troponin T, creatine kinase MB, and ischaemia-modified albumin. Receiver operating characteristic curve (ROC) analysis was used for the sensitivity and specificity of ischaemia-modified albumin in the early diagnosis of acute coronary syndrome. Comparisons between ischaemia-modified albumin and cardiac Troponin T were done between groups.

Results:

The demographics in two groups were not significantly different in most aspects. Compared with non-ischaemic chest pain group, serum levels of ischaemia-modified albumin and cardiac Troponin T were significantly higher in acute coronary syndrome group. ROC analysis showed that ischaemia-modified albumin had a good sensitivity and specificity in early diagnosis of acute coronary syndrome. The level of ischaemia-modified albumin in acute coronary syndrome patients with hypertension was higher than that in non-ischaemic chest pain patients.

Conclusions:

In patients complained with acute chest pain, the serum measurement of ischaemia-modified albumin is potential valuable for the early diagnosis of acute coronary syndrome, especially combined with ECG. The serum level of ischaemia-modified albumin in acute coronary syndrome patients is significantly associated with hypertension.
Anatomic considerations in the management of complete atrioventricular canal
Authors: Wiggins Luke M. , Wang Shuo , Wells Winfield , Starnes Vaughn , Cleveland John D.
Published: October 2023

Objective:

Patients with complete atrioventricular canal have a variable clinical course prior to repair. Many patients balance their circulations well prior to elective repair. Others manifest clinically significant pulmonary over circulation early in life and require either palliative pulmonary artery banding or complete repair. The objective of this study was to assess anatomic features that impact the clinical course of patients.

Methods:

In total, 222 patients underwent complete atrioventricular canal repair between 2012 and 2022 at a single institution. Twenty-seven (12%) patients underwent either pulmonary artery banding (n = 15) or complete repair (n = 12) at less than 3 months of age (Group 1). The remaining 195 (88%) underwent repair after 3 months of age (Group 2). Patient records and imaging were reviewed.

Results:

The median post-operative length of stay following complete repair was 25 [7,46] days for those patients in Group 1 and 7 [5,12] days for those in Group 2 (p < 0.0001). There was relative hypoplasia of left-sided structures in Group 1 versus Group 2. Mean z-score for the ascending aorta was −1.2 (±0.8) versus −0.3 (±0.9) (p < 0.0001), the aortic isthmus was −2.1 (±0.8) versus −1.4 (±0.8) (p = 0.005). The pulmonary valve to aortic valve diameter ratio was median 1.47 [1.38,1.71] versus 1.38 [1.17,1.53] (p 0.008).

Conclusions:

Echocardiographic evaluation of the systemic and pulmonary outflow of patients with complete atrioventricular canal may assist in predicting the clinical course and need for early repair vs pulmonary artery banding.
Identification of the mitochondrial protein POLRMT as a potential therapeutic target of prostate cancer
Authors: Li Xiaojun , Yao Linya , Wang Tao , Gu Xiaolei , Wu Yufan , Jiang Ting
Published: October 2023

RNA polymerase mitochondria (POLRMT) is essential for mitochondrial transcription machinery and other mitochondrial functions. Its expression and potential functions in prostate cancer were explored here. The Cancer Genome Atlas prostate cancer cohort (TCGA PRAD) shows that POLRMT mRNA expression is upregulated in prostate cancer tissues and POLRMT upregulation is correlated with poor patients’ survival. POLRMT mRNA and protein levels were upregulated in local prostate cancer tissues and different primary/immortalized prostate cancer cells. Genetic depletion of POLRMT, using viral shRNA or CRISPR/Cas9 gene editing methods, impaired mitochondrial functions in prostate cancer cells, leading to mitochondrial depolarization, oxidative stress, mitochondria complex I inhibition, and ATP depletion. Moreover, POLRMT depletion resulted in robust inhibition of prostate cancer cell viability, proliferation, and migration, and provoked apoptosis. Conversely, prostate cancer cell proliferation, migration, and ATP contents were strengthened following ectopic POLRMT overexpression. In vivo, intratumoral injection of POLRMT shRNA adeno-associated virus impeded prostate cancer xenograft growth in nude mice. POLRMT silencing, oxidative stress, and ATP depletion were detected in POLRMT shRNA-treated prostate cancer xenograft tissues. IMT1 (inhibitor of mitochondrial transcription 1), the first-in-class POLRMT inhibitor, inhibited prostate cancer cell growth in vitro and in vivo. Together, overexpressed POLRMT is an important mitochondrial protein for prostate cancer cell growth, representing a novel and promising diagnostic and therapeutic oncotarget.
An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization
Authors: Sheppard Carol M. , Goldhill Daniel H. , Swann Olivia C. , Staller Ecco , Penn Rebecca , Platt Olivia K. , Sukhova Ksenia , Baillon Laury , Frise Rebecca , Peacock Thomas P. , Fodor Ervin , Barclay Wendy S.
Published: October 2023

Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth. We find two mutations in different subunits of the influenza polymerase that enable the mutant virus to use a novel host factor, ANP32E, an alternative family member, which is unable to support the wild type polymerase. Both mutations reside in the symmetric dimer interface between two polymerase complexes and reduce polymerase dimerization. These mutations have previously been identified as adapting influenza viruses to mice. Indeed, the evolved virus gains the ability to use suboptimal mouse ANP32 proteins and becomes more virulent in mice. We identify further mutations in the symmetric dimer interface which we predict allow influenza to adapt to use suboptimal ANP32 proteins through a similar mechanism. Overall, our results suggest a balance between asymmetric and symmetric dimers of influenza virus polymerase that is influenced by the interaction between polymerase and ANP32 host proteins.
Proteomics of CKD progression in the chronic renal insufficiency cohort
Authors: Dubin Ruth F. , Deo Rajat , Ren Yue , Wang Jianqiao , Zheng Zihe , Shou Haochang , Go Alan S. , Parsa Afshin , Lash James P. , Rahman Mahboob , Hsu Chi-yuan , Weir Matthew R. , Chen Jing , Anderson Amanda , Grams Morgan E. , Surapaneni Aditya , Coresh Josef , Li Hongzhe , Kimmel Paul L. , Vasan Ramachandran S. , Feldman Harold , Segal Mark R. , Ganz Peter ,   CRIC Study Investigators,   CKD Biomarkers Consortium
Published: October 2023

Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.
The medial septum controls hippocampal supra-theta oscillations
Authors: Király Bálint , Domonkos Andor , Jelitai Márta , Lopes-dos-Santos Vítor , Martínez-Bellver Sergio , Kocsis Barnabás , Schlingloff Dániel , Joshi Abhilasha , Salib Minas , Fiáth Richárd , Barthó Péter , Ulbert István , Freund Tamás F. , Viney Tim J. , Dupret David , Varga Viktor , Hangya Balázs
Published: October 2023

Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic memory. Supra-theta rhythms of hippocampal CA1 are coordinated by local interactions as well as inputs from the entorhinal cortex (EC) and CA3 inputs. However, theta-nested gamma-band activity in the medial septum (MS) suggests that the MS may control supra-theta CA1 oscillations. To address this, we performed multi-electrode recordings of MS and CA1 activity in rodents and found that MS neuron firing showed strong phase-coupling to theta-nested supra-theta episodes and predicted changes in CA1 beta-to-gamma oscillations on a cycle-by-cycle basis. Unique coupling patterns of anatomically defined MS cell types suggested that indirect MS-to-CA1 pathways via the EC and CA3 mediate distinct CA1 gamma-band oscillations. Optogenetic activation of MS parvalbumin-expressing neurons elicited theta-nested beta-to-gamma oscillations in CA1. Thus, the MS orchestrates hippocampal network activity at multiple temporal scales to mediate memory encoding and retrieval.
Unaltered hepatic wound healing response in male rats with ancestral liver injury
Authors: Beil Johanna , Perner Juliane , Pfaller Lena , Gérard Marie-Apolline , Piaia Alessandro , Doelemeyer Arno , Wasserkrug Naor Adi , Martin Lori , Piequet Aline , Dubost Valérie , Chibout Salah-Dine , Moggs Jonathan , Terranova Rémi
Published: October 2023

The possibility that ancestral environmental exposure could result in adaptive inherited effects in mammals has been long debated. Numerous rodent models of transgenerational responses to various environmental factors have been published but due to technical, operational and resource burden, most still await independent confirmation. A previous study reported multigenerational epigenetic adaptation of the hepatic wound healing response upon exposure to the hepatotoxicant carbon tetrachloride (CCl4) in male rats. Here, we comprehensively investigate the transgenerational effects by repeating the original CCl4 multigenerational study with increased power, pedigree tracing, F2 dose-response and suitable randomization schemes. Detailed pathology evaluations do not support adaptive phenotypic suppression of the hepatic wound healing response or a greater fitness of F2 animals with ancestral liver injury exposure. However, transcriptomic analyses identified genes whose expression correlates with ancestral liver injury, although the biological relevance of this apparent transgenerational transmission at the molecular level remains to be determined. This work overall highlights the need for independent evaluation of transgenerational epigenetic inheritance paradigms in mammals.
Structure of native chromatin fibres revealed by Cryo-ET in situ
Authors: Hou Zhen , Nightingale Frank , Zhu Yanan , MacGregor-Chatwin Craig , Zhang Peijun
Published: October 2023

The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determine the in situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density are distributed randomly without any spatial preference. This work will inspire future high-resolution investigations on native chromatin structures in situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.
First demonstration of in-memory computing crossbar using multi-level Cell FeFET
Authors: Soliman Taha , Chatterjee Swetaki , Laleni Nellie , Müller Franz , Kirchner Tobias , Wehn Norbert , Kämpfe Thomas , Chauhan Yogesh Singh , Amrouch Hussam
Published: October 2023

Advancements in AI led to the emergence of in-memory-computing architectures as a promising solution for the associated computing and memory challenges. This study introduces a novel in-memory-computing (IMC) crossbar macro utilizing a multi-level ferroelectric field-effect transistor (FeFET) cell for multi-bit multiply and accumulate (MAC) operations. The proposed 1FeFET-1R cell design stores multi-bit information while minimizing device variability effects on accuracy. Experimental validation was performed using 28 nm HKMG technology-based FeFET devices. Unlike traditional resistive memory-based analog computing, our approach leverages the electrical characteristics of stored data within the memory cell to derive MAC operation results encoded in activation time and accumulated current. Remarkably, our design achieves 96.6% accuracy for handwriting recognition and 91.5% accuracy for image classification without extra training. Furthermore, it demonstrates exceptional performance, achieving 885.4 TOPS/W–nearly double that of existing designs. This study represents the first successful implementation of an in-memory macro using a multi-state FeFET cell for complete MAC operations, preserving crossbar density without additional structural overhead.
Marine viruses disperse bidirectionally along the natural water cycle
Authors: Rahlff Janina , Esser Sarah P. , Plewka Julia , Heinrichs Mara Elena , Soares André , Scarchilli Claudio , Grigioni Paolo , Wex Heike , Giebel Helge-Ansgar , Probst Alexander J.
Published: October 2023

Marine viruses in seawater have frequently been studied, yet their dispersal from neuston ecosystems at the air-sea interface towards the atmosphere remains a knowledge gap. Here, we show that 6.2% of the studied virus population were shared between air-sea interface ecosystems and rainwater. Virus enrichment in the 1-mm thin surface microlayer and sea foams happened selectively, and variant analysis proved virus transfer to aerosols collected at ~2 m height above sea level and rain. Viruses detected in rain and these aerosols showed a significantly higher percent G/C base content compared to marine viruses. CRISPR spacer matches of marine prokaryotes to foreign viruses from rainwater prove regular virus-host encounters at the air-sea interface. Our findings on aerosolization, adaptations, and dispersal support transmission of viruses along the natural water cycle.
The accumulation and growth of Pseudomonas aeruginosa on surfaces is modulated by surface mechanics via cyclic-di-GMP signaling
Authors: Wang Liyun , Wong Yu-Chern , Correira Joshua M. , Wancura Megan , Geiger Chris J. , Webster Shanice S. , Touhami Ahmed , Butler Benjamin J. , O’Toole George A. , Langford Richard M. , Brown Katherine A. , Dortdivanlioglu Berkin , Webb Lauren , Cosgriff-Hernandez Elizabeth , Gordon Vernita D.
Published: October 2023

Attachment of bacteria onto a surface, consequent signaling, and accumulation and growth of the surface-bound bacterial population are key initial steps in the formation of pathogenic biofilms. While recent reports have hinted that surface mechanics may affect the accumulation of bacteria on that surface, the processes that underlie bacterial perception of surface mechanics and modulation of accumulation in response to surface mechanics remain largely unknown. We use thin and thick hydrogels coated on glass to create composite materials with different mechanics (higher elasticity for thin composites; lower elasticity for thick composites) but with the same surface adhesivity and chemistry. The mechanical cue stemming from surface mechanics is elucidated using experiments with the opportunistic human pathogen Pseudomonas aeruginosa combined with finite-element modeling. Adhesion to thin composites results in greater changes in mechanical stress and strain in the bacterial envelope than does adhesion to thick composites with identical surface chemistry. Using quantitative microscopy, we find that adhesion to thin composites also results in higher cyclic-di-GMP levels, which in turn result in lower motility and less detachment, and thus greater accumulation of bacteria on the surface than does adhesion to thick composites. Mechanics-dependent c-di-GMP production is mediated by the cell-surface-exposed protein PilY1. The biofilm lag phase, which is longer for bacterial populations on thin composites than on thick composites, is also mediated by PilY1. This study shows clear evidence that bacteria actively regulate differential accumulation on surfaces of different stiffnesses via perceiving varied mechanical stress and strain upon surface engagement.
Revealing inherent quantum interference and entanglement of a Dirac particle
Authors: Ning Wen , Zheng Ri-Hua , Xia Yan , Xu Kai , Li Hekang , Zheng Dongning , Fan Heng , Wu Fan , Yang Zhen-Biao , Zheng Shi-Biao
Published: October 2023

Although originally predicted in relativistic quantum mechanics, Zitterbewegung can also appear in some classical systems, which leads to the important question of whether Zitterbewegung of Dirac particles is underlain by a more fundamental and universal interference behavior without classical analogs. We here reveal such an interference pattern in phase space, which underlies but goes beyond Zitterbewegung, and whose nonclassicality is manifested by the negativity of the phase space quasiprobability distribution, and the associated pseudospin-momentum entanglement. We confirm this discovery by numerical simulation and an on-chip experiment, where a superconducting qubit and a quantized microwave field respectively emulate the internal and external degrees of freedom of a Dirac particle. The measured quasiprobability negativities agree well with the numerical simulation. Besides being of fundamental importance, the demonstrated nonclassical effects are useful in quantum technology.
γ-Aminobutyric acids (GABA) and serum GABA/AABA (G/A) ratio as potential biomarkers of physical performance and aging
Authors: Lyssikatos Charalampos , Wang Zhiying , Liu Ziyue , Warden Stuart J. , Bonewald Lynda , Brotto Marco
Published: October 2023

Declining physical performance with age and disease is an important indicator of declining health. Biomarkers that identify declining physical performance would be useful in predicting treatment outcomes and identifying potential therapeutics. γ-aminobutyric acid (GABA), a muscle autocrine factor, is a potent inhibitor of muscle function and works as a muscle relaxant. L-α-aminobutyric acid (L-AABA) is a biomarker for malnutrition, liver damage, and depression. We sought to determine if GABA and L-AABA may be useful for predicting physical performance. Serum levels of GABA and L-AABA were quantified in 120 individuals divided by age, sex, and physical capacity into low, average, and high performer groups. Analyses explored correlations between serum levels and physical performance. Both GABA and the ratio of GABA/AABA (G/A), but not AABA, were highly positively associated with age (Pearson correlations r = 0.35, p = 0.0001 for GABA, r = 0.31, p = 0.0007 for G/A, n = 120). GABA showed negative associations in the whole cohort with physical performance [fast gait speed, 6 min walk test (6MWT), PROMIS score, and SF36PFS raw score] and with subtotal and femoral neck bone mineral density. L-AABA was positively associated with usual gait speed, 6MWT, total SPPB score, and SF36PFS raw score in the total cohort of 120 human subjects, also with 6MWT and SF36PFS raw score in the 60 male subjects, but no associations were observed in the 60 females. As both GABA and L-AABA appear to be indicative of physical performance, but in opposite directions, we examined the G/A ratio. Unlike GABA, the G/A ratio showed a more distinct association with mobility tests such as total SPPB score, usual and fast gait speed, 6MWT, and SF36PFS raw score in the males, regardless of age and metabolic status. Serum G/A ratio could be potentially linked to physical performance in the male population. Our findings strongly suggest that GABA, L-AABA, and the G/A ratio in human serum may be useful markers for both age and physical function. These new biomarkers may significantly enhance the goal of identifying universal biomarkers to accurately predict physical performance and the beneficial effects of exercise training for older adults.
rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population
Authors: Clark Jeremy S. C. , Podsiadło Konrad , Sobalska-Kwapis Marta , Marciniak Błażej , Rydzewska Kamila , Ciechanowicz Andrzej , van de Wetering Thierry , Strapagiel Dominik
Published: October 2023

There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m2: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10–5; beta: − 0.0458, 95% confidence interval (CI) − 0.0732 : − 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10–4; beta: − 0.0573, CI − 0.0947 : − 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.
Association between the MTNR1B, HHEX, SLC30A8, and TCF7L2 single nucleotide polymorphisms and cardiometabolic risk profile in a mixed ancestry South African population
Authors: Ngwa Ndonwi Elvis , Matshazi Don Makwakiwe , Davison Glenda Mary , Kengne Andre Pascal , Matsha Tandi Edith
Published: October 2023

Single nucleotide polymorphisms of theTCF7L2,HHEX,SLC30A8,MTNR1B,SLC2A2andGLIS3genes are well established candidate genes for cardiometabolic diseases (CMDs) across different ethnic populations. We investigated their association with CMDs in a mixed ancestry population of South Africa. rs10830963, rs1111875, rs11920090, rs13266634, rs7034200 and rs7903146 SNPs were genotyped by quantitative real time PCR in 1650 participants and Hardy–Weinberg equilibrium (HWE) analyses performed on the SNPs. Diabetes, obesity, hypertension and cardiometabolic traits were compared across genotypes of SNPs in HWE. Linear and logistic regressions adjusting for age, gender and body mass index were used to determine the risk of T2DM, obesity and hypertension. rs7903146 (p = 0.055), rs1111875 (p = 0.465), rs13266634 (p = 0.828), and rs10830963 (p = 0.158) were in HWE. The rs10830963 recessive genotype was able to predict FPG, insulin and HOMA-IR, while the rs1111875 recessive genotype was able to predict total cholesterol, triglyceride, LDL cholesterol and FPG. The rs7903146 recessive genotype was able to predict SBP and LDL cholesterol. The recessive genotypes ofMTNRIBandHHEXSNPs were associated with T2DM traits in the study population and could partially explain the high prevalence of T2DM. Further studies are required to confirm these findings and establish candidate genes in the African population.
Quantifying intracellular glucose levels when yeast is grown in glucose media
Authors: Li Xiang , Heinemann Matthias
Published: October 2023

In Saccharomyces cerevisiae, intracellular glucose levels impact glucose transport and regulate carbon metabolism via various glucose sensors. To investigate mechanisms of glucose sensing, it is essential to know the intracellular glucose concentrations. Measuring intracellular glucose concentrations, however, is challenging when cells are grown on glucose, as glucose in the water phase around cells or stuck to the cell surface can be carried over during cell sampling and in the following attributed to intracellular glucose, resulting in an overestimation of intracellular glucose concentrations. Using lactose as a carryover marker in the growth medium, we found that glucose carryover originates from both the water phase and from sticking to the cell surface. Using a hexokinase null strain to estimate the glucose carryover from the cell surface, we found that glucose stuck on the cell surface only contributes a minor fraction of the carryover. To correct the glucose carryover, we revisited l-glucose as a carryover marker. Here, we found that l-glucose slowly enters cells. Thus, we added l-glucose to yeast cultures growing on uniformly 13C-labeled d-glucose only shortly before sampling. Using GC–MS to distinguish between the two differently labeled sugars and subtracting the carryover effect, we determined the intracellular glucose concentrations among two yeast strains with distinct kinetics of glucose transport to be at 0.89 mM in the wild-type strain and around 0.24 mM in a mutant with compromised glucose uptake. Together, our study provides insight into the origin of the glucose carryover effect and suggests that l-glucose added to the culture shortly before sampling is a possible method that yet has limitations with regard to measurement accuracy.
Exploring the role of our contacts with pets in broadening concerns for animals, nature, and fellow humans: a representative study
Authors: Amiot Catherine E. , Gagné Christophe , Bastian Brock
Published: October 2023

While pet ownership is normative in many occidental countries, whether humans’ proximal contacts with pets have implications for attitudes and behaviors toward other (non pet) animals, nature, and fellow humans, has received limited empirical attention. In a large representative sample, we investigate whether pet ownership and positive contact with pets are associated with more positive attitudes and heightened concerns for non-pet animals, nature, and human outgroups. A cross-sectional questionnaire survey was conducted among Canadian adults (619 pet owners, 450 non-pet owners). Pet owners reported more positive attitudes toward non-pet animals (e.g., wild, farm animals), higher identification with animals, more positive attitudes toward human outgroups, higher biospheric environmental concerns, higher human–environment interdependence beliefs, and lower usual meat consumption. Positive contact with pets was also associated with most of these outcomes. Solidarity with animals, a dimension of identification with animals, emerged as a particularly clear predictor of these outcomes and mediated the associations between positive contact with pets and positive attitudes toward non-pet animals, biospheric, egoistic, and altruistic environmental concerns, human–environment interdependence beliefs, and diet. Our results provide support for the capacity of pets to shape human consideration for a broad range of social issues, beyond the specific context of human-pet relations.
Sodium-glucose co-transporter 2 inhibitor add-on therapy for metformin delays diabetic retinopathy progression in diabetes patients: a population-based cohort study
Authors: Li Jing-Xing , Hung Yu-Tung , Bair Henry , Hsu Shu-Bai , Hsu Chung-Yi , Lin Chun-Ju
Published: October 2023

To investigate how sodium-glucose co-transporter 2 inhibitors (SGLT2is) add-on therapy for metformin affects diabetic retinopathy (DR) progression in patients with type 2 diabetes mellitus (T2DM). This nationwide population-based study conducted from January 1, 2016, to December 31, 2018 involved 3,432,911 adults with T2DM in Taiwan. To adjust for potential confounders, data on sex, age, income, comorbidities, diabetes complication severity index score, staging of kidney disease, anti-diabetic medications, and index year were included. The outcome was DR progression, determined by procedure codes or the addition of ICD-9-CM or ICD-10-CM codes to the medical records of the patients during the study. Sensitivity analyses were performed to validate the findings. The adjusted hazard ratio (aHR) of DR progression was 0.89 for the SGLT2is add-on group, relative to the control group [95% confidence interval (CI) 0.81–0.99, P = 0.026]. The Kaplan–Meier curve of the cumulative incidence rate showed that the cumulative incidence of DR progression was considerably decreased in the SGLT2is cohort (log-rank P = 0.0261). The use of SGLT2is for less than 1 year and 1–2 years were associated with a significant increase in the risk of DR progression (aHR 1.56 and 1.88, respectively); however, the risk markedly reduced if the SGLT2is regimen was used for more than 2 years (aHR 0.41, 95% Cl 0.35–0.48; P < 0.001). The serial sensitivity analysis showed consistent findings. The aHR of DR progression was 0.82 for the SGLT2is cohort relative to the non-SGLT2is cohort based on the fundoscopy or indirect ophthalmoscopy findings within 1 year before the outcome date (95% Cl 0.71–0.95; P = 0.009). Co-administration of metformin and SGLT2is may reduce the risk of DR progression. Short-term use of SGLT2is may markedly increase the risk of DR, whereas prolonged use SGLT2is may significantly decrease it.