bluuebunny/crossref_metadata_2025 huggingface dataset:
„Trans* ist plural“ – Reflexionen aus der klinischen Arbeit
Authors: Breu Franziska , Grebe Jörn
Published: December 2022

Vor dem Hintergrund ihrer Tätigkeit in der Spezialsprechstunde für Geschlechtsdysphorie in der Kinder- und Jugendpsychiatrie am Universitätsklinikum Hamburg-Eppendorf wenden sich die Autor*innen Fragen rund um die Komplexität und Heterogenität in der Behandlung von geschlechtsdysphorischen Kindern und Jugendlichen – insbesondere in der frühen Adoleszenz – zu. Hierbei wird der spannungsreiche Spagat zwischen der Notwendigkeit, als Behandler*in einen reflexiven Verstehensprozess der jeweils individuellen Geschlechtsdysphorie und/oder Transidentität anzustoßen, sowie dem oftmals zentralen Wunsch nach einer zeitnahen Indikation körpermedizinischer Maßnahmen aufseiten der Patient*innen diskutiert. Die Autor*innen plädieren für eine neutrale, offene Haltung gegenüber den vielschichtigen Konflikten, Belastungen und komplexen Symptomatiken der Jugendlichen, um eine verantwortungsvolle Entscheidung für Transitionsschritte treffen zu können.
Ablehnen, Anprangern, Beleidigen: Sexualitätsbezogene Meinungsdynamiken im Internet
Authors: Lemke Richard
Published: December 2022

Zu Beginn des Beitrags werden drei Beispiele vorgestellt, anhand derer die Spezifika sexualitätsbezogener Meinungsdynamiken im Internet illustriert werden. Speziell Meinungsäußerungen auf Social-Media-Seiten können aufgrund der gesteigerten Redebereitschaft im Internet sowie ihrer Rolle bei der Schätzung von Meinungsverteilungen als ein Katalysator in sexualitätsbezogenen Meinungsdiskursen fungieren: Sie können Minderheitsmeinungen und Versprachlichung von Sexualität begünstigen, gleichzeitig aber auch durch Empörungswellen und personifizierte Angriffe andere zur Verstummung bringen. Es wird anschließend für eine Verstärkung der demoskopischen Erforschung sexualitätsbezogener öffentlicher Meinung argumentiert, weil der öffentlichen Meinung im Rahmen von Sexualität verschiedene Funktionen zukommen: Sie trägt zur Ausformung von Engagement in gesellschaftlichen Debatten bei, bildet eine Komponente des (sexuellen) Minderheitenstresses in einer Gesellschaft und stellt – auch mit Blick auf Scham – einen Bewertungsrahmen sexueller Handlungen dar. Der Beitrag schließt mit Empfehlungen für Wissenschaft, Bildung und Praxis.
Stress und Alterung
Authors: Wolf Alfred
Published: December 2022

Der biologische Alterungsprozess besteht aus Änderungen von molekularen
Strukturen und deren Funktionen bei unzureichenden Reparaturmechanismen. Dieser
katabole Prozess fördert die Vulnerabilität für
altersabhängige Erkrankungen wie degenerative Gehirnerkrankungen.
Verstärkend wirken dabei chronischer Stress, psychische Belastung,
Genetik/Epigenetik, endokrine Alterung und bestimmte Lebensstilfaktoren.
Dauerhaft verstärkte Stressexposition verändert den gesamten
Zellstoffwechsel und erhöht dadurch das Risiko für den Verlust
von physischer und emotionaler Lebensqualität, organischer
Gesamtfunktion und Mortalität.
Ophthalmological Findings in Joubert Syndrome and Related Disorders
Authors: Ceravolo Ida , Granata Francesca , Gitto Eloisa , Iapadre Giulia , Chimenz Roberto , Giannitto Nino , Mancuso Alessio , Ceravolo Maria Domenica , Macchia Tommaso La , Rissotto Federico , Farello Giovanni , Cuppari Caterina
Published: December 2022

Joubert syndrome (JS) is a rare genetic condition characterized by congenital malformation of the mid-hindbrain, cerebellar ataxia, hypotonia, oculomotor apraxia, hypoplasia of the cerebellar vermis resulting in breathing defects, ataxia, and delayed development. Ophthalmological examination reveals eye involvement with nystagmus and retinal defects. Genetic counseling is important for the prevention of new cases. Great advances have been made in recent years. Management is symptomatic and multidisciplinary. In the present review, we discussed the most frequent ophthalmological anomalies associated with JS and speculated on the role of ciliary physiology in eye development.
Ionization-induced optical heterogeneity and ion-like direct emission in 1-nm silicon nanoparticle grains: Prospect for fast optical modulation
Authors: Mantey Kevin , Morgan Huw , Nayfeh Ammar , Bahceci Ersin , Nayfeh Munir H.
Published: December 2022

Silicon, a highly symmetric and homogeneous material, does not exhibit fast optical modulation. Recent classical electrodynamics simulations, however, demonstrated transient optical heterogeneity in silicon nanostructures, in which a high-density of excitonic electron–hole pair plasma and charge is created. The phenomenon, however, requires a specific particle size (∼100 nm diameter) and a high-density (1023/cc) plasma. We examine here the quantum aspect of the heterogeneity in 1-nm Si nanoparticles. Due to the small number of atoms, 1 nm nanoparticles are amenable to the Hartree–Fock first principle atomistic quantum theory simulations procedure, while single ionization events are sufficient to provide high charge density (2 × 1021/cc). The simulations show that the charge distribution in singly charged 1-nm particles is nonlinear and heterogeneous, accompanied with structural distortion that produces an electric dipole moment. Electronically, the simulations show that the single charge induces stationary Coulomb states that riddle the bandgap of the neutral particle, with dipole-allowed transitions, effectively inducing partial conducting-like behavior. Optically, when the charge is produced by ionizing UV radiation, the ionized particle survives and exhibits both extended (wide-band) as well as atomic- or ion-like sharp emission, in agreement with infrared polarimetry and spectroscopy observations in the solar coronal holes, as well as under synchrotron irradiation. Not only do ionized Si nanoparticles (charged nanosilicon grains) afford fast optical modulations, but they may also prove pivotal for understanding features of interstellar medium, observed throughout the Milky Way and other galaxies, including spectroscopic and material composition, as well as neutral hydrogen abundancy.
Spin Hall nano-oscillators based on synthetic skyrmions imprinted in Co nanodisc
Authors: Choi Byoung , Aryal Mukesh , Rasmussen Ben , Choi Minyeong , Hong Yang-Ki
Published: December 2022

Spin Hall nano-oscillators utilizing the synthetic spin textures imprinted in nanomagnets are demonstrated by numerical investigations. The imprinting is achieved by locally manipulating the magnetic anisotropy and the interfacial Dzyaloshinskii–Moriya interaction (DMI). The resulting spin texture is equivalent to a Néel-type skyrmion and is topologically stable to thermal fluctuations at finite temperatures. The eigenoscillation of the synthetic skyrmion can be activated by the spin-orbit torques induced by the spin Hall effect, and an eigenfrequency of up to ∼1.5 GHz is achieved. The eigenmode of the skyrmion resonance is found to be associated with the counter-clockwise rotational motion of the local magnetization. Our result demonstrates the working principle of using synthetic nanomagnets in spintronics applications.
Fidelity or infidelity?
Authors: Yoon Sun Kyoung
Published: December 2022

This article examines the controversy over The Vegetarian (Han 2015), Deborah Smith’s English translation of Han Kang’s Korean novel,
채식주의자 Chaesikjuuija (2007). The translation, winner of the Man Booker International Prize in 2016, provoked a heated discussion in South Korea. A close analysis of three influential articles – Cho (2017), B. Kim (2017), and W. Kim (2018) – shows how the debates on the supposed mistranslation of The Vegetarian are dominated by a preoccupation with fidelity and literal translation. They dismiss the translator’s interpretation or transformation, regarding accuracy or fidelity as the sole criterion for a good translation. Significantly, the critics’ advocacy of literal translation, and hence their objections to The Vegetarian, reflect three levels of political anxiety: over ‘superior’ translation, over ‘English’ translation, and over a female translator’s ‘feminist’ translation.
Multi-mode Bus Coupling Architecture of Superconducting Quantum Processor
Authors: Zhao Changhao , He Yongcheng , Geng Xiao , He Kaiyong , Dai Genting , Liu Jianshe , Chen Wei
Published: December 2022

Resonators in circuit quantum electrodynamics systems naturally carry multiple modes, which may have non-negligible influence on qubit parameters and device performance. While new theories and techniques are under investigation to deal with the multi-mode effects in circuit quantum electrodynamics systems, novel engineering designs are also proposed featuring multi-mode resonators to achieve enhanced functionalities of superconducting quantum processors. In this work, multi-mode bus coupling architecture is proposed, in which superconducting qubits are coupled to multiple bus resonators to gain larger coupling strength. Application of multi-mode bus coupler can help improve iSWAP gate fidelity and gate speed beyond the limit of single-mode scenario. The proposed multi-mode bus coupling architecture is compatible with a scalable variation of the traditional bus coupling architecture. It opens up new possibilities for realization of scalable superconducting quantum computation with circuit quantum electrodynamics systems.
Al-fumarate metal-organic frameworks adsorbent for removal of organic compound and gas storage
Authors: Loan Nguyen Thu , Thi Hiep Nguyen , Thi Thu Huong Tran , Thi Dieu Thuy Ung , Thi Thuong Huyen Tran , Le Hoang Tan Doan , Liem Nguyen Quang
Published: December 2022

Metal-organic frameworks (MOFs) have attracted a great amount of attention due to their unique properties, including high porosity, large surface area, and flexible frameworks. These special properties are desirable in many applications such as adsorption, catalysis, drug delivery, and gas storage. Herein, Al-fumarate MOFs were synthesised from the reaction of aluminium sulphate with fumaric acid at 65 °C for 1 h. X-ray diffraction (XRD), N2-adsorption, scanning electronic microscope (SEM), thermogravimetric analysis (TGA), and UV–vis spectrometer were used to characterise the physicochemical properties of the prepared adsorbent materials. The obtained results indicated that the Al-fumarate MOFs possess good water stability and can adsorb/remove over 70% of Rose Bengal under UV–light irradiation. Gas adsorption/storage experiments revealed that Al-fumarate MOFs also exhibited high CO2 and CH4 uptakes of ∼59 cm3 g−1 and 17 cm3 g−1 at 303 K and ∼805 Torr (∼1 bar), respectively. The synthesised Al-fumarate MOFs obtained both excellent photocatalytic activity and high gas adsorption/storage that are due to the large surface area (∼1100 m2 g)−1 and high porosity (0.65 cm3 g)−1. Thus, these Al-fumarate MOFs are very promising in the fields of photocatalysis for wastewater treatment and of gas adsorption/storage.
Tackling Data Disclosure Comparatively – Conference ‘Vectors of Data Disclosure’ in Munich, 27 and 28 June 2022
Authors: Illek Lukas
Published: December 2022

The disclosure of personal data and the decision by individuals to do so is ubiquitous. Which aspects influence this decision? How is disclosure regulated in different jurisdictions and how far do protective mechanisms go in favor of the ‘data subject’? These questions only scratch the surface of topics which the University of Passau research project ‘Vectors of Data Disclosure’ is addressing comparatively and with regard to Brazil, China, the European Union, Ghana, Japan, Russia, Switzerland, and the United States since January 2021. The project takes an interdisciplinary approach and aims to tackle these questions by combining cultural, legal, and business information systems perspectives. The project is led by Moritz Hennemann, Daniela Wawra, Kai von Lewinski and Thomas Widjaja. Concluding the first 18 months of the project, the project team invited international experts from different disciplines to Munich, offering a platform to discuss new insights and receive feedback on the project’s preliminary research results so far.
TikTok, #IUD, and User Experience With Intrauterine Devices Reported on Social Media
Authors: Wu Jenny , Trahair Esmé , Happ Megan , Swartz Jonas
Published: December 2022

TikTok, a video-sharing application, offers a growing platform for contraception-related content. The top 100 videos tagged “#IUD” were compiled using a web-scraping application. User demographics and video content were analyzed by two independent reviewers, with a third to arbitrate differences. More videos had a negative tone (37.8%) about intrauterine devices (IUDs) than positive (19.4%), and 27.6% mentioned distrust of health care professionals. Of videos conveying patient experiences, all had a negative or ambiguous tone and 96.8% highlighted pain and other side effects related to IUDs. Videos scored low on information health quality (1.2/5 on DISCERN) and averaged 73.8% in understandability and 17.7% in actionability on PEMAT (Patient Education Materials Assessment Tool). #IUD videos on TikTok often portray negative experiences related to pain and informed consent.
Vax the Max, a Gamification Intervention for COVID-19 Vaccination Task Engagement in the Inpatient Setting
Authors: Raikhel A. Vincent , Blau Kevin , Alberty Katherine , Cornia Paul , Rodriguez Rudolph A. , Steinberg Kenneth P. , Wu Chenwei
Published: December 2022

The development of vaccines for SARS-CoV-2 has offered game-changing protection from severe disease and death from COVID-19. Despite efforts to vaccinate individuals in the ambulatory setting, a sizable minority of the US population remains unvaccinated for COVID-19. For unvaccinated patients, hospitalization for non-COVID-19 illness offers another opportunity for vaccination. In the summer of 2021, the authors noted that COVID-19 vaccination rate for medicine inpatients at their hospital had fallen to 5.3 vaccine doses administered per 4-week block. In response, they created Vax the Max, a gamification program of COVID-19 vaccination tasks where internal medicine resident teams were awarded points for completing these tasks. Residents were anonymously surveyed after participation. The hospital demonstrated higher rates of administering the initial COVID-19 vaccine dose and completing the vaccine series in the inpatient setting per 4-week plan-do-study-act cycle after implementation of Vax the Max (5.3 versus 8.8 doses per plan-do-study-act cycle). Among residents, 76.8% reported that Vax the Max spurred their COVID-19 task engagement, and 66% reported that a similar gamification model could be utilized for a different clinical task in the future. An increase was observed in the COVID-19 vaccination rate for medicine inpatients after launching the Vax the Max competition. This occurred in the setting of resident turnover every 4 weeks, which normally makes practice sustainment more challenging. Despite this, a high degree of engagement was produced by itinerant residents. There is potential to explore similar gamification approaches involving resident physicians in areas of quality improvement and patient safety.
Effects of Morning or Evening Narrow-band Blue Light on the Compensation to Lens-induced Hyperopic Defocus in Chicks
Authors: Nickla Debora L. , Wang Xia , Rucker Frances , Chen William , Taylor Christopher
Published: December 2022

SIGNIFICANCE

Exposure to blue light before bedtime is purported to be deleterious to various aspects of human health. In chicks, blue evening light stimulated ocular growth, suggesting a role in myopia development. To further investigate this hypothesis, we asked if brief blue light altered the compensatory responses to hyperopic defocus.

PURPOSE

Previous work showed that several hours' evening exposure to blue light stimulated ocular growth in chicks, but morning exposure was only effective at a lower illuminance. By contrast, rearing in blue light has inhibited ocular growth in untreated eyes and eyes exposed to form deprivation or defocus. We studied the effects of brief exposures to blue light on the compensation to hyperopic defocus.

METHODS

Chicks wore monocular negative lenses (−10 D) starting at age 10 days. They were subsequently exposed to blue light (460 nm) for 4 hours in the morning or evening for 8 to 9 days (“dim,” 200 lux[morning, n = 9; evening, n = 11]; “bright,” 600 lux[morning, n = 8; evening, n = 20]); controls wore lenses in white light (n = 14). Ultrasonography was done on days 1, 5, 8, and 9 for “evening” groups and days 1, 6, and 8 for “morning.” All data are reported as interocular differences (experimental minus fellow eyes). Refractions were measured on the last day.

RESULTS

For evening exposure, dim blue light enhanced the axial compensation at all times (change in axial length: day 6: 465 vs. 329 μm/9 days, analysis of variance P < .001, P = .03; day 9: 603 vs. 416 μm/9 days, analysis of variance P < .001; P < .05). Bright blue light had a transient inhibitory effect (day 5: 160 vs. 329 μm; P < .005). Refractive errors were consistent with axial growth, with dim causing more myopia than bright (−9.4 vs. −4.7 D; P < .05). Morning blue light had no significant effect.

CONCLUSIONS

We speculate that these findings reflect a complex interaction between illuminance, defocus, and time of day.
Integrated Host/Microbe Metagenomics Enables Accurate Lower Respiratory Tract Infection Diagnosis in Critically Ill Children
Authors: Mick Eran , Tsitsiklis Alexandra , Kamm Jack , Kalantar Katrina L. , Caldera Saharai , Lyden Amy , Tan Michelle , Detweiler Angela M. , Neff Norma , Osborne Christina M. , Williamson Kayla M. , Soesanto Victoria , Leroue Matthew , Maddux Aline B. , Simões Eric A. F. , Carpenter Todd C. , Wagner Brandie D. , DeRisi Joseph L. , Ambroggio Lilliam , Mourani Peter M. , Langelier Charles R.
Published: December 2022

BACKGROUND

Lower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging since non-infectious respiratory illnesses appear clinically similar and existing microbiologic tests are often falsely negative or detect incidentally-carried microbes, resulting in antimicrobial overuse and adverse outcomes. Lower airway metagenomics has the potential to detect host and microbial signatures of LRTI. Whether it can be applied at scale and in a pediatric population to enable improved diagnosis and treatment remains unclear.

METHODS

We used tracheal aspirate RNA-sequencing to profile host gene expression and respiratory microbiota in 261 children with acute respiratory failure. We developed a gene expression classifier for LRTI by training on patients with an established diagnosis of LRTI (n=117) or of non-infectious respiratory failure (n=50). We then developed a classifier that integrates the host LRTI probability, abundance of respiratory viruses, and dominance in the lung microbiome of bacteria/fungi considered pathogenic by a rules-based algorithm.

RESULTS

The host classifier achieved a median AUC of 0.967 by cross-validation, driven by activation markers of T cells, alveolar macrophages and the interferon response. The integrated classifier achieved a median AUC of 0.986 and increased the confidence of patient classifications. When applied to patients with an uncertain diagnosis (n=94), the integrated classifier indicated LRTI in 52% of cases and nominated likely causal pathogens in 98% of those

CONCLUSIONS

Lower airway metagenomics enables accurate LRTI diagnosis and pathogen identification in a heterogeneous cohort of critically ill children through integration of host, pathogen, and microbiome features.
Identifying secondary findings in PET/CT reports in oncological cases: A quantifying study using automated Natural Language Processing
Authors: Sekler Julia , Kämpgen Benedikt , Reinert Christian Philipp , Daul Andreas , Gückel Brigitte , Dittmann Helmut , Pfannenberg Christina , Gatidis Sergios
Published: December 2022

Background

Because of their accuracy, positron emission tomography/computed tomography (PET/CT) examinations are ideally suited for the identification of secondary findings but there are only few quantitative studies on the frequency and number of those.

Most radiology reports are freehand written and thus secondary findings are not presented as structured evaluable information and the effort to manually extract them reliably is a challenge. Thus we report on the use of natural language processing (NLP) to identify secondary findings from PET/CT conclusions.

Methods

4,680 anonymized German PET/CT radiology conclusions of five major primary tumor entities were included in this study. Using a commercially available NLP tool, secondary findings were annotated in an automated approach. The performance of the algorithm in classifying primary diagnoses was evaluated by statistical comparison to the ground truth as recorded in the patient registry. Accuracy of automated classification of secondary findings within the written conclusions was assessed in comparison to a subset of manually evaluated conclusions.

Results

The NLP method was evaluated twice. First, to detect the previously known principal diagnosis, with an F1 score between 0.65 and 0.95 among 5 different principal diagnoses.

Second, affirmed and speculated secondary diagnoses were annotated, and the error rate of false positives and false negatives was evaluated. Overall, rates of false-positive findings (1.0%-5.8%) and misclassification (0%-1.1%) were low compared with the overall rate of annotated diagnoses. Error rates for false-negative annotations ranged from 6.1% to 24%. More often, several secondary findings were not fully captured in a conclusion. This error rate ranged from 6.8% to 45.5%.

Conclusions

NLP technology can be used to analyze unstructured medical data efficiently and quickly from radiological conclusions, despite the complexity of human language. In the given use case, secondary findings were reliably found in in PET/CT conclusions from different main diagnoses.
Osmotic fragility duringin vitroerythrocyte cytotoxicity induced by aluminium chloride, lead acetate or mercuric chloride in hyposmolar sucrose media
Authors: Igbokwe Nanacha Afifi , Igbokwe Ikechukwu Onyebuchi
Published: December 2022

Erythrocyte death by eryptosis or erythronecrosis may induce erythrocyte shrinking or swelling with increase in osmotic resistance or fragility as indication of cytotoxicity. We investigated heterogeneous cytotoxic outcomes during in vitro exposure of goat erythrocytes to aluminium chloride, lead acetate or mercuric chloride using erythrocyte osmotic fragility (EOF) testing. The metallic salt solution (MSS) was added to 4.0 μL of high (100 mosmol/L) and low (250 mosmol/L) hyposmolar sucrose media at 0.3 or 0.4 mosmol/L concentration during testing of the osmotic fragility of 5.0 μL of blood from 10 goats. Hemolysis induced in the media (with and without MSS) was estimated in the supernatant with spectrophotometer at 540 nm. Osmotic stabilization or destabilization was calculated with probability for each test. Inducible osmotic resistance (IOR) was the ratio of mean stabilization to destabilization in both high and low hyposmolar media. Each MSS induced both osmotic resistance (stabilization) and fragility (destabilization) in varied media concentrations, with greater likelihood (P) of stabilization (0.93) or destabilization (0.77) in high or low media hyposmolarity, respectively. The EOF outcomes of the goats diverged within the group. High IOR induced by mercuric chloride (2.90) and low IOR by lead acetate (0.07) and aluminium chloride (0.04) reflected high stabilizing and destabilizing outcomes, respectively. In conclusion, MSS induced dual EOF outcomes (stabilization or destabilization) on the fragility domain, suggesting occurrence of both eryptosis (as stabilization) and erythronecrosis (as destabilization) at low exposure level, whereby biphasic, nonmonotonic or hormetic response to MSS toxic action might exist.
Neuron-astrocyte metabolic coupling facilitates spinal plasticity and maintenance of persistent pain
Authors: Marty-Lombardi Sebastián , Lu Shiying , Ambroziak Wojciech , Wende Hagen , Schrenk-Siemens Katrin , DePaoli-Roach Anna A. , Hagenston Anna M. , Tappe-Theodor Anke , Simonetti Manuela , Kuner Rohini , Fleming Thomas , Siemens Jan
Published: December 2022

Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated in neuronal plasticity and memory formation in the CNS, but neither its involvement in pathological pain nor in spinal plasticity has been tested. Here, we report a novel form of neuroglia signaling involving spinal astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation of the metabolic signaling molecule PTG exclusively in spinal astrocytes. PTG drove glycogen build-up in astrocytes, and blunting glycogen accumulation and turnover byPtggene deletion reduced pain-related behaviors and promoted faster recovery by shortening pain maintenance. Furthermore, mechanistic analyses revealed that glycogen dynamics is a critically required process for maintenance of pain by facilitating neuronal plasticity in spinal lamina 1 neurons. Finally, metabolic analysis indicated that glycolysis and lactate transfer between astrocytes and neurons fuels spinal neuron hyperexcitability.

Spinal glycogen-metabolic cascades therefore hold therapeutic potential to alleviate pathological pain.
High resolution cryo-EM structures of two potently SARS-CoV-2 neutralizing monoclonal antibodies of same donor origin that vary in neutralizing Omicron variants
Authors: Rencilin Clayton Fernando , Ansari Mohammad Yousuf , Chatterjee Arnab , Deshpande Suprit , Mukherjee Sohini , Singh Randhir , Jayatheertha Sowrabha , Reddy Poorvi M. , Das Payel , Hingankar Nitin , Rathore Deepak , Varadarajan Raghavan , Bhattacharya Jayanta , Dutta Somnath
Published: December 2022

While vaccines have by large been found to effective against the evolving SARS-CoV-2 variants, the profound and rapid effectivity of monoclonal antibodies (mAbs) in significantly reducing hospitalization to severe disease outcomes have also been demonstrated. In the present study, by high resolution cryo-electron microscopy (cryo-EM), we examined the structural insights of two trimeric spike (S) protein bound mAbs isolated from an Indian convalescent individual infected with ancestral SARS-CoV-2 which we recently reported to potently neutralize SARS-CoV-2 from its ancestral form through highly virulent Delta form however different in their ability to neutralize Omicron variants. Our findings showed binding and conformational heterogeneities of both the mAbs (THSC20.HVTR04 and THSC20.HVTR26) bound to S trimer in its apo and hACE-2 bound forms. Additionally, cryo-EM resolved structure assisted modeling highlighted key residues associated with the ability of these two mAbs to neutralize Omicron variants. Our findings highlighted key interacting features modulating antigen-antibody interacting that can further aid in structure guided antibody engineering to enhance their breadth and potency.

Highlights

Two potent human mAbs obtained from a single donor differ binding to Omicron spikes

Pattern of binding and conformation of these mAbs bound to full length spike differs

Antibody binding alters the conformational states of S trimer in its apo and hACE-2 bound forms.

Cryo-EM structure guided modeling highlighted correlates of interacting residues associated with resistance and sensitivity of BA.1, BA.2, BA.4/BA.5 resistance and sensitivity against these mAbs.
New high-resolution maps show that rubber causes significant deforestation
Authors: Wang Yunxia , Hollingsworth Peter M. , Zhai Deli , West Christopher D. , Green Jonathan , Chen Huafang , Hurni Kaspar , Su Yufang , Warren-Thomas Eleanor , Xu Jianchu , Ahrends Antje
Published: December 2022

Understanding the impacts of cash crop expansion on natural forest is of fundamental importance. However, for most crops there are no remotely-sensed global maps1, and global deforestation impacts are estimated using models and extrapolations. Natural rubber is an example of a major commodity for which deforestation impacts have been highly uncertain, with estimates differing more than five-fold1–4. Here we harnessed earth observation satellite data and cloud computing5to produce the first high-resolution maps of rubber and associated deforestation covering all Southeast Asia. Our maps indicate that rubber-related forest loss has been significantly underestimated in policy, by the public and in recent reports6–8. Our direct remotely-sensed observations show that deforestation for rubber is two to threefold higher than suggested by figures currently widely used for setting policy4. With over 3.76 million hectares of forest loss for rubber since 1993 (2.77 [2.5-3 95% CI] million hectares since 2000), and over 1 million hectares of rubber plantations established in Key Biodiversity Areas, the impacts of rubber on biodiversity and ecosystem services in Southeast Asia are extensive. Thus, rubber deserves more attention in domestic policy, within trade agreements and in incoming due diligence regulations.
The PRALINE database: Protein and Rna humAn singLe nucleotIde variaNts in condEnsates
Authors: Vandelli Andrea , Segura Magdalena Arnal , Monti Michele , Fiorentino Jonathan , Broglia Laura , Colantoni Alessio , de Groot Natalia Sanchez , Burgas Marc Torrent , Armaos Alexandros , Tartaglia Gian Gaetano
Published: December 2022

Biological condensates are membraneless organelles with different material properties. Proteins and RNAs are the main components, but most of their interactions are still unknown. Here we introduce PRALINE, a database for the interrogation of proteins and RNAs contained in stress-granules, processing bodies, and other assemblies including droplets and amyloids. PRALINE provides information about the predicted and experimentally validated protein-protein, protein-RNA and RNA-RNA interactions. For proteins, it reports the liquid-liquid phase separation and liquid-solid phase separation propensities. For RNAs, it provides information on predicted secondary structure content. PRALINE shows detailed information on human single-nucleotide variants, their clinical significance and presence in protein and RNA binding sites, and how they can affect condensates’ physical properties.

Availability

PRALINE is freely accessible on the web athttp://alvinlee.bio.uniroma1.it/praline.

Supplementary information

General information is athttp://alvinlee.bio.uniroma1.it/praline/about, where we provide a detailed description of the datasets and the tools employed in the database. Data provided in PRALINE are available athttp://alvinlee.bio.uniroma1.it/praline/downloads. The tutorial is athttp://alvinlee.bio.uniroma1.it/praline/tutorial.
Scope+: An open source generalizable architecture for single-cell atlases at sample and cell levels
Authors: Yin Danqing , Cao Yue , Chen Junyi , Mak Candice L.Y. , Yu Ken H.O. , Lin Yingxin , Zhang Jiaxuan , Li Jia , Ho Joshua W. K. , Yang Jean Y.H.
Published: December 2022

With the recent advancement in single-cell technologies and the increased availability of integrative tools, challenges arise in easy and fast access to large collections of cell atlas. Existing cell atlas portals rarely are open sourced and adaptable, and do not support meta-analysis at cell level. Here, we present an open source, highly optimised and scalable architecture, named Scope+, to allow quick access, meta-analysis and cell-level selection of the atlas data. We applied this architecture to our well-curated 5 million Covid-19 blood and immune cells, as a portal, Covidscope (https://covidsc.d24h.hk/). We achieved efficient access to atlas-scale data via three strategies, such as server-side rendering, novel database optimization strategies and an innovative architectural design. Scope+ serves as an open source architecture for researchers to build on with their own atlas, and demonstrated its capability in the Covidscope portal for an effective meta-analysis to atlas data at cellular resolution for reproducible research.
Evaluating the impact of minimum unit pricing for alcohol on road traffic accidents in Scotland: a controlled interrupted time series study
Authors: Manca Francesco , Parab Rakshita , Mackay Daniel , Fitzgerald Niamh , Lewsey Jim
Published: December 2022

Background

On 1stMay 2018, Scotland implemented Minimum Unit Pricing (MUP) of £0.50 per unit of alcohol to lower alcohol consumption and related harms, and reduce health inequalities. We assessed the impact of MUP on road traffic accidents (RTAs) after 20 months of implementation.

Methods

A controlled interrupted time series design was used to evaluate the impact of MUP on RTAs (total, fatal, night-time) in Scotland and any effect modification across socio-economic deprivation groups. RTAs in England and Wales (E&W) were used as a control group. Covariates of severe weather events, bank holidays, seasonal and underlying trends were included.

Results

In Scotland, MUP implementation was associated with a 7.2% (95% CI: 0.9%,13.7% P=0.03) increase in the total number of RTAs. For the corresponding period in E&W, there was a 0.9% increase (95% CI: -2.3%,3.2% P=0.75). It is implausible that MUP caused this increase in RTAs, with the most likely explanation of these results being that unmeasured time-varying confounding affected Scotland and E&W differently. There was no evidence of differential impacts of MUP by level of socio-economic deprivation.

Conclusion

The introduction of MUP in Scotland was not associated with a lower level of RTAs.
Spatial organization of the mouse retina at single cell resolution
Authors: Choi Jongsu , Li Jin , Ferdous Salma , Liang Qingnan , Moffitt Jeffrey R. , Chen Rui
Published: December 2022

The visual signal processing in the retina requires the precise organization of diverse neuronal types working in concert. We performed spatial transcriptomic profiling of over 100,000 cells from the mouse retina, uncovering the spatial distribution of all major retina cell types with over 100 cell subtypes. Our data revealed that the retina is organized in a laminar structure at the major cell type and subgroup level, both of which has strong correlation with the birth order of the cell. In contrast, overall random dispersion of cells within sub-laminar layers indicates that retinal mosaics are driven by dendritic field patterning rather than neuron soma placement. Through the integration of single cell transcriptomic and spatial data, we have generated the first comprehensive spatial single cell reference atlas of the mouse retina, a resource to the community and an essential step toward gaining a comprehensive understanding of the mechanism of retinal function.

Graphical Abstract
Robust Online Multiband Drift Estimation in Electrophysiology Data
Authors: Windolf Charlie , Paulk Angelique C. , Kfir Yoav , Trautmann Eric , Garcia Samuel , Meszéna Domokos , Muñoz William , Hardstone Richard , Caprara Irene , Jamali Mohsen , Boussard Julien , Williams Ziv M. , Cash Sydney S. , Paninski Liam , Varol Erdem
Published: December 2022

High-density electrophysiology probes have opened new possibilities for systems neuroscience in human and non-human animals, but probe motion (or drift) while recording poses a challenge for downstream analyses, particularly in human recordings. Here, we improve on the state of the art for tracking this drift with an algorithm termedDREDge(DecentralizedRegistration ofElectrophysiologyData) with four major contributions. First, we extend previous decentralized methods to exploitmultibandinformation, leveraging the local field potential (LFP), in addition to spikes detected from the action potentials (AP). Second, we show that the LFP-based approach enables registration atsub-secondtemporal resolution. Third, we introduce an efficientonlinemotion tracking algorithm, allowing the method to scale up to longer and higher spatial resolution recordings, which could facilitate real-time applications. Finally, we improve therobustnessof the approach by accounting for the nonstationarities that occur in real data and by automating parameter selection. Together, these advances enable fully automated scalable registration of challenging datasets from both humans and mice.
Mechanisms of HIV-1 Integrase Resistance to Dolutegravir and Potent Inhibition of Drug Resistant Variants
Authors: Li Min , Passos Dario Oliveira , Shan Zelin , Smith Steven J. , Sun Qinfang , Biswas Avik , Choudhuri Indrani , Strutzenberg Timothy S. , Haldane Allan , Deng Nanjie , Li Zhaoyang , Zhao Xue Zhi , Burke Terrence R. , Levy Ronald M. , Hughes Stephen H. , Craigie Robert , Lyumkis Dmitry
Published: December 2022

HIV-1 infection depends on the integration of viral DNA into host chromatin. Integration is mediated by the viral enzyme integrase and is blocked by integrase strand transfer inhibitors (INSTIs), first-line antiretroviral therapeutics widely used in the clinic. Resistance to even the best INSTIs is a problem and the mechanisms of resistance are poorly understood. Here, we analyze combinations of the mutations E138K, G140A/S, and Q148H/K/R, which confer resistance to INSTIs. The investigational drug 4d more effectively inhibited the mutants compared with the approved drug Dolutegravir (DTG). We present 11 new cryo-EM structures of drug resistant HIV-1 intasomes bound toDTGor4d, with better than 3 Å resolution. These structures, complemented with free energy simulations, virology, and enzymology, explain the mechanisms ofDTGresistance involving E138K+G140A/S+Q148H/K/R and show why4dmaintains potency better thanDTG. These data establish a foundation for further development of INSTIs that potently inhibit resistant forms in integrase.
Older age is associated with a shift from ventral to dorsal PCC in pathways connecting the DMN with visual and limbic areas and a directionality shift in pathways connecting the DMN with sensorimotor areas
Authors: Goelman Gadi , Dan Rotem , Bezdicek Ondrej , Jech Robert , Ekstein Dana
Published: December 2022

Alterations in the default mode network (DMN) are known to associated with aging and with neurological and psychiatric diseases. We assessed age-dependent changes in interactions within the DMN and between the DMN with other brain areas, and correlations of these interactions with a battery of neuropsychological tests to formulate a macroscopic model of ageing.

Using a novel multivariate analysis method, enabling determination of directed pathways, on resting-state functional MRI data from fifty young and thirty-one old healthy individuals, we identified directed intra- and inter-DMN directed pathways that differed between the groups and used their correlations with neuropsychological tests to infer their behavioral meaning.

Pathways connecting the DMN with visual and limbic regions in old subjects engaged at BOLD low frequency and involved the dorsal PCC. In young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) and the DMN, were efferent in young subjects (DMNSM). Most inter-DMN pathways in the old subjects, correlated with reduced speed and working memory and, were DMN efferent (DMN>).

We suggest a macroscopic model of aging centered in the DMN. It suggests that the reduced sensorimotor efferent, probably brought about from reduced physical activity, and the increased need to control such activities by the mPFC, causes a higher dependency on external versus internal cues. This results in a shift from ventral to dorsal PCC of inter-DMN pathways. Consequently, the model combines physical activity with ageing.
Scaling behaviors of deep learning and linear algorithms for the prediction of stroke severity
Authors: Bourached Anthony , Bonkhoff Anna K. , Schirmer Markus D. , Regenhardt Robert W. , Bretzner Martin , Hong Sungmin , Dalca Adrian V. , Giese Anne-Katrin , Winzeck Stefan , Jern Christina , Lindgren Arne G. , Maguire Jane , Wu Ona , Rhee John , Kimchi Eyal Y. , Rost Natalia S.
Published: December 2022

Introduction

Deep learning has allowed for remarkable progress in many medical scenarios. Since deep learning prediction models often require 105-107examples, it is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller. Such stroke outcome predictions however could be particularly instrumental in guiding acute clinical and rehabilitation care decisions. We here compared the capacities of classically used linear and novel deep learning algorithms in their prediction of stroke severity.

Methods

Our analyses relied on a total of 1,430 patients assembled from the MRI-GENIE collaboration and a Massachusetts General Hospital-based study. The outcome of interest was NIHSS-based stroke severity in the acute phase after ischemic stroke onset, which we predict by means of MRI-derived lesion location. We automatically derived lesion segmentations from diffusion-weighted clinical MRI scans, performed spatial normalization and included a principal component analysis (PCA) step, retaining 95% of the variance of the original data. We then repeatedly separated a train, validation, and test set to investigate the effects of sample size, we subsampled the train set to 100, 300, and 900 and trained the algorithms to predict the NIHSS score for each sample size with regularized linear regression and an 8-layered neural network. We selected hyperparameters on the validation set. We evaluated model performance based on the explained variance (R-squared) in the test set.

Results

While linear regression performed significantly better for a sample size of 100 patients, deep learning started to significantly outperform linear regression when trained on 900 patients. Average prediction performance improved by ∼20% when increasing the sample size 9x (maximum for 100 patients: 0.279 ± 0.005 (R2, 95% confidence interval), 900 patients: 0.337 ± 0.006).

Conclusions

For sample sizes of 900 patients, deep learning showed a higher prediction performance than typically employed linear methods. These findings suggest the existence of non-linear relationships between lesion location and stroke severity that can be utilized for an improved prediction performance for larger sample sizes.
Real-world evidence of mortality and survival rates in 256 individuals with APDS
Authors: Hanson Jennifer , Bonnen Penelope E.
Published: December 2022

Activated Phosphoinositide 3-kinase Delta Syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants inPIK3CDandPIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function (GOF) variants in thePIK3CDgene while loss of function (LOF) variants inPIK3R1have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. A Kaplan-Meier survival analysis for APDS showed the conditional survival rate at the age of 20 was 87%, age 30 was 74%, age 40 and 50 were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The mortality data suggests that the standard of care treatment for APDS, immunoglobulin replacement therapy, appears to prevent most deaths due to severe infection, however, new treatments are needed to mitigate the risk of death from lymphoma and other cancers. This analysis based on real world evidence gathered from the medical literature is the largest study of survival for APDS to date.
Stakeholder perspectives on interventions to improve HIV Pre-Exposure Prophylaxis uptake and continuation in Lesotho: A participant-ranked preferences study
Authors: Geldsetzer Pascal , Chebet Joy J. , Chase Rachel P. , Tarumbiswa Tapiwa , Maponga Chivimbiso , Mandara Esther , Bärnighausen Till , McMahon Shannon A.
Published: December 2022

Background

Low uptake and high discontinuation rates remain major obstacles to realizing the potential of Pre-Exposure Prophylaxis (PrEP) in changing the trajectory of the HIV epidemic in sub-Saharan Africa. Evidence on how PrEP could be successfully delivered has thus far mainly focused on key target groups rather than the general adult population. Set in the HIV-hyperendemic country of Lesotho, which is currently rolling out PrEP for the general adult population, this study aimed to determine stakeholders’ views on which are the most important barriers and most promising interventions to achieving high PrEP uptake and continuation.

Methods and findings

We conducted a card sorting and ranking exercise with 155 local stakeholders to identify key barriers and interventions. Stakeholders were a purposive sample of PrEP policy makers and implementing partners (n=7), healthcare providers (n=51), and end-users (n=97). End-users included adults who were currently using PrEP (n=55), formerly using PrEP (n=36), and were offered PrEP by a healthcare provider but declined (n=6). Participants sorted pre-selected interventions and barriers to PrEP coverage into three piles – most, somewhat, and least important. After sorting, participants ranked interventions and barriers in the “most important” piles in ascending order of significance. Ranked preferences were analyzed as voting data to identify the smallest set of candidates for which each candidate in the set would win a two-candidate election against any candidate outside the set. Participants viewed a lack of PrEP awareness as the most important barrier to PrEP uptake for women, and a fear of HIV testing for men. Community-based HIV testing was ranked as the most promising intervention to improve PrEP uptake for both men and women. Perceived or experienced stigma was seen as an important barrier for PrEP continuation for both men and women, with an additional important barrier for men being daily activities that compete with the time or mental bandwidth needed to take a daily pill. Adherence counseling and multi-month PrEP prescriptions were seen as the most promising interventions to improve PrEP continuation.

Conclusions

Our findings suggest community-based activities that generate PrEP demand (community-based HIV testing and mass media campaigns), reinforced with facility-based follow-up (counseling and multi-month prescription) could be promising interventions to improve PrEP uptake and continuation in PrEP programs that are aimed at the general adult population. The views of the wide range of stakeholders that participated in this study could provide a useful starting point for design and implementation choices of PrEP delivery programs for the general adult population.