bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploiting the LSPR effect for an enhanced photocatalytic hydrogen evolution reaction
Authors: Ye Ziwei , Xu Zehong , Yue Wenhui , Liu Xinyu , Wang Lingzhi , Zhang Jinlong
Published: December 2022

This article summarizes recent advances in the development of plasmonic metal–semiconductor photocatalysts with an emphasis on the enhancing mechanism related to the localized surface plasmon resonance (LSPR) effect.
The mechanisms of chromogranin B-regulated Cl− homeostasis
Authors: Jiang Qiu-Xing , Yadav Gaya
Published: December 2022

Chloride is the most abundant inorganic anions in almost all cells and in human circulation systems. Its homeostasis is therefore important for systems physiology and normal cellular activities. This topic has been extensively studied with chloride loaders and extruders expressed in both cell surfaces and intracellular membranes. With the newly discovered, large-conductance, highly selective Cl− channel formed by membrane-bound chromogranin B (CHGB), which differs from all other known anion channels of conventional transmembrane topology, and is distributed in plasma membranes, endomembrane systems, endosomal, and endolysosomal compartments in cells expressing it, we will discuss the potential physiological importance of the CHGB channels to Cl− homeostasis, cellular excitability and volume control, and cation uptake or release at the cellular and subcellular levels. These considerations and CHGB's association with human diseases make the CHGB channel a possible druggable target for future molecular therapeutics.
Form and function of archaeal genomes
Authors: Bell Stephen D.
Published: December 2022

A key maxim in modernist architecture is that ‘form follows function'. While modernist buildings are hopefully the product of intelligent design, the architectures of chromosomes have been sculpted by the forces of evolution over many thousands of generations. In the following, I will describe recent advances in our understanding of chromosome architecture in the archaeal domain of life. Although much remains to be learned about the mechanistic details of archaeal chromosome organization, some general principles have emerged. At the 10–100 kb level, archaeal chromosomes have a conserved local organization reminiscent of bacterial genomes. In contrast, lineage-specific innovations appear to have imposed distinct large-scale architectural features. The ultimate functions of genomes are to store and to express genetic information. Gene expression profiles have been shown to influence chromosome architecture, thus their form follows function. However, local changes to chromosome conformation can also influence gene expression and therefore, in these instances, function follows form.
Nicht korrigierte Entgleisung der Shuntvene bezüglich Durchmesser, Länge, Kinking und Drainagefunktion
Authors: Krönung Gerhard
Published: December 2022

Shuntvenen zeigen, wie seit Langem als Remodeling beschrieben, typischerweise und nicht unerwartet, sondern biologisch herleitbar, zeitlebens mehr oder weniger ausgeprägte, morphologische und/oder funktionelle Veränderungen. Überschreiten diese dabei trotz alltäglich stattfindendem, notabene zuwendendem Gebrauch, bestimmte Grenzen, nicht immer, aber immer wieder scheinbar auch ohne jede Reaktion aller eigentlich dauernd irgendwie Beteiligten, drängt sich das durchaus wertende Adjektiv „verwahrlost“ vielleicht genau deshalb bei distanzierter Betrachtung geradezu auf. Hierher gehört natürlich auch die dezidierte Entscheidung des Patienten, den Shunt eventuell auch über Jahre nicht revidieren zu lassen. Die späte Korrektur, wenn sie denn überhaupt noch versucht wird, erfordert bei Extrembefunden, wie dem hier beschriebenen, ein hohes Maß an shuntchirurgischer Erfahrung und Zuwendung. Die beginnende Nummerierung des kurzen Untertitels lässt weitere Fälle erwarten.
Förderpreis Nephrologische Pflege 2023
Authors: Schäfer Christian
Published: December 2022

Die Thieme Gruppe schreibt im Jahr 2023 wieder den Förderpreis Nephrologische Pflege aus und stiftet das Preisgeld von 1500 Euro.
Vitamin D und sekundärer Hyperparathyreoidismus (sHPT) bei CKD im Spiegel der Zeit
Authors: Brandenburg Vincent Matthias
Published: December 2022

Ein Vitamin-D-Mangel trägt bei Patienten mit chronischer Nierenerkrankung (CKD: Chronic Kidney Disease) entscheidend zur Entstehung eines sekundären Hyperparathyreoidismus (sHPT) bei. Der Ausgleich dieses Mangels bei CKD-Patienten mit sHPT durch eine regelmäßige Vitamin-D-Substitution hat sich in den letzten Jahrzehnten in Form einer Springprozession vollzogen: Jeder Schritt vor und zurück hat neue, wichtige Erkenntnisse zu den komplexen Zusammenhängen zwischen der medikamentösen Substitution von Vitamin D und den Effekten auf das Parathormon (PTH) und den Knochenstoffwechsel erbracht. Heute können die unerwünschten Nebenwirkungen der Vitamin-D-Therapie (Hyperkalzämie, Hyperphosphatämie) besser kontrolliert werden. Trotzdem steht der Nachweis des klinischen Nutzens immer noch aus, da in den klinischen Studien bisher keine „harten“ Endpunkte (kardiovaskuläre Ereignisse, Frakturen, Mortalität etc.) untersucht worden sind.
Ausblick Kalziphylaxie
Authors: Ketteler Markus , Brandenburg Vincent Matthias
Published: December 2022

Die Kalziphylaxie ist eine seltene, mit hoher Mortalität assoziierte Erkrankung der Haut, die hauptsächlich bei Patienten mit fortgeschrittenen Nierenerkrankungen bzw. im Dialysestadium auftritt. Sie ist charakterisiert durch ausgesprochen schmerzhafte, nekrotisierende kutane Ulzerationen. Histomorphologische Kennzeichen sind vor allem ubiquitäre Verkalkungen der Media kleiner Arteriolen und gelegentlich auch in den angrenzenden Geweben. Zu den Differenzialdiagnosen gehören vaskulitische Hautveränderungen, Pyoderma gangraenosum, diabetische Ulzerationen und Cholesterinembolien. Hier geben aber die Patientenanamnese (Niereninsuffizienz, Dialyse, sowie der Einsatz von Vitamin K-Antagonisten) und die Schmerzhaftigkeit wesentliche Hinweise in Richtung Kalziphylaxie. Anfangs bestand die Vermutung, dass die Kalziphylaxie ursächlich einem schweren Hyperparathyreoidismus zugeordnet werden müsse, Registeranalysen haben diese Auffassung aber deutlich relativiert. Vielmehr scheinen Faktoren wie eine überschießende Kalzium- und Phosphatbilanz, ein adynamer Knochenstoffwechsel, Entzündungsprozesse, Verkalkungshemmermangel und therapeutischer Vitamin-K-Antagonismus als Trigger eine kausale Rolle zu spielen. Die aktuellen therapeutischen Ansätze (Natrium-Thiosulfat, Vitamin K2, ggf. Bisphosphonate, ggf. Kalzimimetika oder Parathyreoidektomie) werden möglicherweise mittelfristig um SNF472 (parenterales Phytat), einem pyrophosphatähnlichen Hexaphosphat, ergänzt, das aktuell in prospektiven Studien in der Indikation der Kalziphylaxiebehandlung evaluiert wird.
Evaluation of a real-time computer-aided polyp detection system during screening colonoscopy: AI-DETECT study
Authors: Ahmad Ahmir , Wilson Ana , Haycock Adam , Humphries Adam , Monahan Kevin , Suzuki Noriko , Thomas-Gibson Siwan , Vance Margaret , Bassett Paul , Thiruvilangam Kowshika , Dhillon Angad , Saunders Brian P.
Published: December 2022

Background Polyp detection and resection during colonoscopy significantly reduce long-term colorectal cancer risk. Computer-aided detection (CADe) may increase polyp identification but has undergone limited clinical evaluation. Our aim was to assess the effectiveness of CADe at colonoscopy within a bowel cancer screening program (BCSP).

Methods This prospective, randomized controlled trial involved all eight screening-accredited colonoscopists at an English National Health Service (NHS) BCSP center (February 2020 to December 2021). Patients were randomized to CADe or standard colonoscopy. Patients meeting NHS criteria for bowel cancer screening were included. The primary outcome of interest was polyp detection rate (PDR).

Results 658 patients were invited and 44 were excluded. A total of 614 patients were randomized to CADe (n = 308) or standard colonoscopy (n = 306); 35 cases were excluded from the per-protocol analysis due to poor bowel preparation (n = 10), an incomplete procedure (n = 24), or a data issue (n = 1). Endocuff Vision was frequently used and evenly distributed (71.7 % CADe and 69.2 % standard). On intention-to-treat (ITT) analysis, there was a borderline significant difference in PDR (85.7 % vs. 79.7 %; P = 0.05) but no significant difference in adenoma detection rate (ADR; 71.4 % vs. 65.0 %; P = 0.09) for CADe vs. standard groups, respectively. On per-protocol analysis, no significant difference was observed in these rates. There was no significant difference in procedure times.

Conclusions In high-performing colonoscopists in a BCSP who routinely used Endocuff Vision, CADe improved PDR but not ADR. CADe appeared to have limited benefit in a BCSP setting where procedures are performed by experienced colonoscopists.
Das Redy-Dialysegerät
Authors: Sander Ullrich
Published: December 2022

Erste Überlegungen, gebrauchtes Dialysat zu regenerieren, reichen bis ins Jahr 1966 zurück. Malcolm Roberts beschrieb dies in dem Satz: „Sorbents consisting of zirconium phosphate, hydrated zirconium oxide, and carbon combined with urease were placed in a cartridge“.
10 Jahre Deutsches Lipoproteinapherese-Register (DLAR)
Authors: Schettler Volker
Published: December 2022

Bereits im Jahr 2000 angedacht, aber erst seit 2012 umgesetzt: Das Deutsche Lipoproteinapherese-Register (DLAR). Wir freuen uns mit Ihnen, dass dieses weltweit einmalige Apherese-Register nun 2022 sein 10-jähriges Jubiläum feiert.
A Thirteen-Year Analysis of Facial Fractures among Professional Soccer Players
Authors: Kozlowski Konrad M. , Rosston Peter A. , Park Asher C. , Hakimi Amir A. , Socolovsky Leandro , Wong Brian J-F
Published: December 2022

This study aims to identify the epidemiology and effects of facial fractures on return to play (RTP) in Major League Soccer (MLS) and the English Premier League (EPL). A total of 39 MLS players and 40 EPL players who sustained facial fractures from 2007 to 2019 were identified. Data on player demographics, the injury, and the impact of their injury on RTP were collected. Elbow-to-head was the most common mechanism of injury (20.3%). The most common fracture involved the nasal bone (48.3%). Most players (90%) RTP the same season. Players who sustained nasal fractures missed significantly fewer games (p < 0.001) than those who suffered other craniofacial fractures. Players treated surgically missed significantly more games (3.21 vs. 0.71, p = 0.006) and days (30.1 vs. 8.70, p = 0.002) than those managed nonoperatively. Significantly more EPL players who sustained facial fractures wore headgear upon RTP compared to MLS players (82% vs. 56%, p <0 .01). Most professional soccer players who sustain a facial fracture RTP the same season, but their recovery time can vary depending on the type of fracture, injury management, or injury severity. Our findings can help inform future craniofacial injury management as well as guidelines on player safety and fracture prevention.
TBHP/KI-Promoted Oxidative Cyclization of α-Aminoketones for One-Pot Synthesis of Substituted 2-Acyloxazoles
Authors: Zheng Jiecheng , Zhu Dali , Gan Lin Ling , Gan Zongjie , Yang Zhangyou , Chen Huali , Wang Wei
Published: December 2022

A metal-free and facile synthesis of substituted 2-acyloxazole derivatives from α-aminoketones was developed via a TBHP/KI-promoted oxidative cyclization. This procedure proceeded smoothly under mild conditions and a broad scope of 2-acyloxazoles were obtained in moderate to good yields.
Two-photon spectral modulation via temporal manipulation: Quantum optical synthesis of spectral modes from temporal square waves
Authors: Jin Rui-Bo , Oshima Hiroki , Yagisawa Takumi , Yabuno Masahiro , Miki Shigehito , China Fumihiro , Terai Hirotaka , Shimizu Ryosuke
Published: December 2022

Precise manipulation of the time–frequency modes of entangled photons is crucial for future quantum science and technologies. Recently, the frequency-domain-quantum-optical-synthesis (FD-QOS) method was demonstrated by creating a superposition of different joint temporal amplitudes: those temporal distributions can be controlled by manipulating the joint spectral amplitude in 2D frequency space via a Fourier optical relation. This FD-QOS method provides an efficient, flexible, and easy-to-control way to precisely modulate the temporal distributions of the entangled photon in an ultrafast region. However, manipulation of only the temporal modes is not sufficient for various applications in quantum information, since spectral modulations are also needed on many occasions. Here, we present a proof-of-concept experiment of two-photon spectral modulation via temporal manipulation of a biphoton wave packet. This protocol, called time-domain-quantum-optical-synthesis (TD-QOS), is achieved by adjusting the relative phases between two joint temporal distributions. In addition, the two-photon joint spectral distributions are characterized by measuring the joint spectral intensities and Hong–Ou–Mandel interferences. The combination of FD-QOS and TD-QOS enables complete control over the biphoton states. Our work would further develop quantum technologies that rely on the time–frequency modes of entangled photons.
Large increase in photo-induced conductivity of two-dimensional electron gas at SrTiO3 surface with BiFeO3 topping layer
Authors: Laohana Peerawat , Polin Siwat , Jindata Warakorn , Rasritat Aissara , Eknapakul Tanachat , Leuasoongnoen Pimchanok , Pinitsoontorn Supree , Janphuang Pattanaphong , Saenrang Wittawat , Meevasana Worawat
Published: December 2022

In this work, we study and compare the photo-induced conductivity of a two-dimensional electron gas (2DEG) at the bare surface of SrTiO3 (STO) and in the heterostructure of BiFeO3 (BFO) and STO, where BFO was deposited by radio frequency magnetron sputtering. The photo-induced conductance of the BFO/STO interface shows a large increase which is 20.62 times more than the sum of photo-induced conductance from each individual BFO thin film and STO crystal. Since this photo-induced conductance of the BFO/STO heterostructure can be adjusted to become higher and lower by applying an electric field to the top surface, we attribute this large increase to the strong photo-induced electrical polarization of BFO. With the two-point setup of positive bias and negative bias, the conductivity also exhibits diode-like behavior where the forward and backward resistances are different. This work provides methods to interplay between light irradiation, electric field, and conductivity in all-oxide electronics.
Dual-bias modulation heterodyne Kelvin probe force microscopy in FM mode
Authors: Miyazaki Masato , Sugawara Yasuhiro , Li Yan Jun
Published: December 2022

The use of a heterodyne detection scheme in Kelvin probe force microscopy (KPFM) is an effective way for enhancing the performance of KPFM. However, this detection scheme generally has difficulty in detecting the first- and second-harmonic electrostatic forces simultaneously. To overcome this problem, we propose dual-bias modulation heterodyne frequency modulation KPFM (DM-hetero-FM KPFM), in which dual AC biases at 2f1±fm are applied between the tip and the sample. DM-hetero-FM KPFM enables us to measure the contact potential difference and capacitance gradient simultaneously at high frequencies (in the MHz range) beyond the bandwidth of phase-lock loop. Moreover, the present method allows us to perform it in the open-loop mode, which is highly desired for performing KPFM on semiconductors or in liquids at high frequencies.
Characteristics of air flow driven by the water free surface in a free-flow spillway tunnel
Authors: Gong Jing , Zhou Maolin , Deng Jun , Wei Wangru
Published: December 2022

Air is transported downstream by the water flow in a free-flow spillway tunnel, resulting in high negative pressure, which causes gate vibration and cavitation. In this research work, a physical model of a free-flow spillway tunnel was used to investigate the effects of water surface velocity and the area residual of tunnel cross sections on air movements. The results demonstrate that the air velocity distribution forms an S-shaped curve. As the water surface velocity increases or the area residual decreases, the air velocity increases, and the relative action height of the drag force of water flow on the air increases as well. The air velocity distribution is divided into two exponential distributions at the position where the air velocity drops by 0.2 times that of the water surface velocity. Two formulas for calculating the air velocity of the corresponding exponential distributions are developed. Subsequently, an algorithm for the air demand is presented, and the relative error compared to the reference data was less than ±20%. These results provide a reference for free-flow spillway tunnel ventilation shaft design.
Formation of printing defects and their effects on mechanical properties of additively manufactured metal alloys
Authors: Mooraj Shahryar , Dong Jiaqi , Xie Kelvin Y. , Chen Wen
Published: December 2022

Printing defects are known to degrade the performance of additively manufactured (AM) alloys. Thus, a thorough understanding of their formation mechanisms and effects on the mechanical properties of AM materials is critically needed. Here, we take CoCrFeNi high-entropy alloy as a model material and print this alloy by laser powder bed fusion over a wide range of printing conditions. We reveal the processing windows for the formation of different printing defects including lack of fusion (LOF), keyhole, and solidification cracking. LOF and keyholes can be well correlated with insufficient and excessive laser energy density inputs, respectively. Of particular interest, we observe that solidification cracks only emerge at the medium laser energy density region, where the porosity is minimal yet the grain size and misorientation are relatively large. Such observation is rationalized within the framework of Rappaz–Drezet–Gremaud solidification theory. Among the above printing defects, solidification cracks in AM CoCrFeNi result in less degradation of mechanical properties compared with LOF and keyholes due to their different defect densities and resultant capabilities of coalescence. Our work provides fundamental insight into understanding the physical origins underlying the formation of printing defects and their impacts on the mechanical properties of AM metals and alloys.
SELENBP1 overexpression in the prefrontal cortex underlies negative symptoms of schizophrenia
Authors: Kim Soojin , Kim Seong-Wook , Bui Mai Anh Thi , Kim Yeji , Kim Minsoo , Park Jung-Cheol , Kim Nam-Heon , Pyeon Gyeong Hee , Jo Yong Sang , Jang Jaewon , Koh Hae-Young , Jeong Chae-Hong , Kang Moonkyung , Kang Hyo Jung , Lee Yong-Woo , Stockmeier Craig A. , Seong Je Kyung , Woo Dong Ho , Han Jung-Soo , Kim Yeon-Soo
Published: December 2022

The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports. However, no causative link between SELENBP1 and schizophrenia has yet been established. Here, we provide evidence linking the upregulation of SELENBP1 in the PFC of mice with the negative symptoms of schizophrenia. We verified the levels ofSELENBP1transcripts in postmortem PFC brain tissues from patients with schizophrenia and matched healthy controls. We also generated transgenic mice expressing human SELENBP1 (hSELENBP1 Tg) and examined their neuropathological features, intrinsic firing properties of PFC 2/3-layer pyramidal neurons, and frontal cortex (FC) electroencephalographic (EEG) responses to auditory stimuli. Schizophrenia-like behaviors in hSELENBP1 Tg mice and mice expressingSelenbp1in the FC were assessed.SELENBP1transcript levels were higher in the brains of patients with schizophrenia than in those of matched healthy controls. The hSELENBP1 Tg mice displayed negative endophenotype behaviors, including heterotopias- and ectopias-like anatomical deformities in upper-layer cortical neurons and social withdrawal, deficits in nesting, and anhedonia-like behavior. Additionally, hSELENBP1 Tg mice exhibited reduced excitabilities of PFC 2/3-layer pyramidal neurons and abnormalities in EEG biomarkers observed in schizophrenia. Furthermore, mice overexpressingSelenbp1in FC showed deficits in sociability. These results suggest that upregulation of SELENBP1 in the PFC causes asociality, a negative symptom of schizophrenia.
Repurposed dihydroorotate dehydrogenase inhibitors with efficacy against drug-resistant
Acinetobacter baumannii
Authors: Russo Thomas A. , Umland Timothy C. , Deng Xiaoyi , El Mazouni Farah , Kokkonda Sreekanth , Olson Ruth , Carlino-MacDonald Ulrike , Beanan Janet , Alvarado Cassandra L. , Tomchick Diana R. , Hutson Alan , Chen Hong , Posner Bruce , Rathod Pradipsinh K. , Charman Susan A. , Phillips Margaret A.
Published: December 2022

New antimicrobials are needed for the treatment of extensively drug-resistant
Acinetobacter baumannii
. The de novo pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is a validated drug target for malaria and human autoimmune diseases. We provide genetic evidence that
A. baumannii
DHODH (
Ab
DHODH) is essential for bacterial survival in rodent infection models. We chemically validate the target by repurposing a unique library of ~450 triazolopyrimidine/imidazopyrimidine analogs developed for our malaria DHODH program to identify 21 compounds with submicromolar activity on
Ab
DHODH. The most potent (DSM186, DHODH IC
50
28 nM) had a minimal inhibitory concentration of ≤1 µg/ml against geographically diverse
A. baumannii
strains, including meropenem-resistant isolates. A structurally related analog (DSM161) with a long in vivo half-life conferred significant protection in the neutropenic mouse thigh infection model. Encouragingly, the development of resistance to these compounds was not identified in vitro or in vivo. Lastly, the X-ray structure of
Ab
DHODH bound to DSM186 was solved to 1.4 Å resolution. These data support the potential of
Ab
DHODH as a drug target for the development of antimicrobials for the treatment of
A. baumannii
and potentially other high-risk bacterial infections.
PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation
Authors: Seo Yoona , Kang Yura , Ham Youngwook , Kim Mi-Hwa , Kim Seong-Jun , Yoon Seung Kew , Jang Sung Key , Park Jong Bae , Cho Sungchan , Kim Jong Heon
Published: December 2022

The liver-specific microRNA, miR-122, plays an essential role in the propagation of hepatitis C virus (HCV) by binding directly to the 5′-end of its genomic RNA. Despite its significance for HCV proliferation, the host factors responsible for regulating miR-122 remain largely unknown. In this study, we identified the cellular RNA-binding protein, ELAVL1/HuR (embryonic lethal-abnormal vision-like 1/human antigen R), as critically contributing to miR-122 biogenesis by strong binding to the 3′-end of miR-122. The availability of ELAVL1/HuR was highly correlated with HCV proliferation in replicon, infectious, and chronically infected patient conditions. Furthermore, by screening a kinase inhibitor library, we identified rigosertib, an anticancer agent under clinical trials, as having both miR-122-modulating and anti-HCV activities that were mediated by its ability to target polo-like kinase 1 (PLK1) and subsequently modulate ELAVL1/HuR-miR-122 signaling. The expression of PLK1 was also highly correlated with HCV proliferation and the HCV positivity of HCC patients. ELAVL1/HuR-miR-122 signaling and its mediation of PLK1-dependent HCV proliferation were demonstrated by performing various rescue experiments and utilizing an HCV mutant with low dependency on miR-122. In addition, the HCV-inhibitory effectiveness of rigosertib was validated in various HCV-relevant conditions, including replicons, infected cells, and replicon-harboring mice. Rigosertib was highly effective in inhibiting the proliferation of not only wild-type HCVs, but also sofosbuvir resistance-associated substitution-bearing HCVs. Our study identifies PLK1-ELAVL1/HuR-miR-122 signaling as a regulatory axis that is critical for HCV proliferation, and suggests that a therapeutic approach targeting this host cell signaling pathway could be useful for treating HCV and HCV-associated diseases.
Prevalence of Post-Coronavirus Disease Condition 12 Weeks After Omicron Infection Compared With Negative Controls and Association With Vaccination Status
Authors: Nehme Mayssam , Vetter Pauline , Chappuis François , Kaiser Laurent , Guessous Idris ,   for the CoviCare Study Team, Nehme Mayssam , Vetter Pauline , Braillard Olivia , Assal Frederic , Lador Frederic , Guerreiro Ivan , Coen Matteo , Agoritsas Thomas , Reny Jean-Luc , Graf Christophe , Courvoisier Delphine S , Benzakour Lamyae , Genevay Stéphane , Lauper Kim , Salamun Julien , Spechbach Hervé , Jacquerioz Frederique , Grira Marwène , Favale Riccardo , Bondolfi Guido , Tardin Aglaé , Soccal Paola M , Zekry Dina , Stringhini Silvia , Meyer Philippe , Poku Nana Kwabena , Landis Basile N , Sandoval José , Bel Michael , Perisa Damir , Chappuis François
Published: December 2022

Background

Post-coronovirus disease (COVID) symptoms can persist several months after severe acute respiratory syndrome coronavirus 2 infection. Little is known, however, about the prevalence of post-COVID condition following infections from Omicron variants and how this varies according to vaccination status. This study evaluates the prevalence of symptoms and functional impairment 12 weeks after an infection by Omicron variants (BA.1 and BA.2) compared with negative controls tested during the same period.

Methods

Outpatient individuals who tested positive or negative for COVID-19 infection between December 2021 and February 2022 at the Geneva University Hospitals were followed 12 weeks after their test date.

Results

Overall, 11.7% of Omicron cases had symptoms 12 weeks after the infection compared with 10.4% of individuals who tested negative during the same period (P < .001), and symptoms were much less common in vaccinated versus nonvaccinated individuals with Omicron infection (9.7% vs 18.1%; P < .001). There were no significant differences in functional impairment at 12 weeks between Omicron cases and negative controls, even after adjusting for multiple potential confounders.

Conclusions

The differential prevalence of post-COVID symptoms and functional impairment attributed to Omicron BA.1 and BA.2 infection is low when compared with negative controls. Vaccination is associated with lower prevalence of post-COVID symptoms.
Incidence and associated risk factors for systemic drug levels with inhaled aminoglycoside therapy
Authors: Schultheis Jennifer M , Durham Mary E , Kram Shawn J , Kuhrt Michelle , Gilstrap Daniel L , Parish Alice , Green Cynthia L , Kram Bridgette L
Published: December 2022

Objectives

To characterize the incidence of and risk factors for a detectable drug level (DDL) in patients that received inhaled aminoglycoside therapy.

Methods

This retrospective, single-centre study included adult patients who received at least one dose of an inhaled aminoglycoside with a drug level during inpatient hospitalization. Patients were excluded if they received an aminoglycoside intravenously within 7 days or if the drug level was not drawn within 4 h of the next dose. A repeated measures logistic regression model evaluated the association between potential risk factors and a DDL.

Results

Among 286 drug levels, 88 (30.8%) drug levels were detectable. In multivariable analysis, cystic fibrosis (CF) (OR: 3.03; 95% CI: 1.10–8.35), chronic kidney disease (CKD) (OR: 4.25; 95% CI: 1.84–9.83), lung transplant recipient (OR: 3.08; 95% CI: 1.09–8.73), mechanical ventilation (OR: 2.99; 95% CI: 1.25–7.15) and tobramycin (OR: 5.26; 95% CI: 2.35–11.78) were associated with higher odds of a DDL. Among those with a DDL, inhaled aminoglycoside type and drug level concentration were not associated with acute kidney injury (P = 0.161).

Conclusions

Among 286 drug levels identified among inpatients receiving inhaled aminoglycoside therapy, 88 (30.8%) unique drug levels were detectable. Based on the results of this study, periodic trough concentrations should be considered for patients receiving inhaled aminoglycoside therapy with CF, CKD, lung transplantation, mechanical ventilation or tobramycin.
Redshift evolution of galaxy group X-ray properties in the Simba simulations
Authors: Robson Dylan , Davé Romeel
Published: December 2022

We examine the evolution of intragroup gas rest-frame X-ray scaling relations for group-sized haloes (M500 = 1012.3–1015  M⊙) in the Simba galaxy formation simulation. X-ray luminosity LX versus M500 shows increasing deviation from self-similarity from z = 3 → 0, with M500 < 1013.5 M⊙ haloes exhibiting a large reduction in LX and slight increase in X-ray luminosity-weighted temperature TX. These shifts are driven by a strong drop in fgas with time for these haloes, and coincides with the onset of Simba’s black hole (BH) jet feedback, occurring when MBH > 107.5 M⊙ and Eddington ratio <0.2, in group haloes at z ∼ 1.5. The connection with BH feedback is corroborated by fBH ≡ MBH/M500 in M500 < 1013.5 M⊙ haloes being strongly anticorrelated with LX and fgas at $z\lesssim 1.5$. This is further reflected in the scatter of LX − TX: haloes with small fBH lie near self-similarity, while those with the highest fBH lie furthest below. Turning off jet feedback results in mostly self-similar behaviour down to z = 0. For the X-ray weighted metallicity ZX, stellar feedback impacts the enrichment of halo gas. Finally, halo profiles show that jet feedback flattens the electron density and entropy profiles, and introduces a core in X-ray surface brightness, particularly at M500 < 1013.5 M⊙. This argues that in Simba, intragroup X-ray evolution is largely driven by jet feedback removing hot gas from the cores of massive groups, and expelling gas altogether in less massive groups.
The velocity distribution of outflows driven by choked jets in stellar envelopes
Authors: Pais Matteo , Piran Tsvi , Nakar Ehud
Published: December 2022

Many stripped envelope supernovae (SNe) present a signature of high-velocity material responsible for broad absorption lines in the observed spectrum. These include SNe that are associated with long gamma-ray bursts (LGRBs) and low-luminosity GRBs (llGRBs), and SNe that are not associated with GRBs. Recently it was suggested that this high-velocity material originates from a cocoon that is driven by a relativistic jet. In LGRBs, this jet breaks out successfully from the stellar envelope, while in llGRBs and SNe that are not associated with GRBs the jet is choked. Here we use numerical simulations to explore the velocity distribution of an outflow that is driven by a choked jet, and its dependence on the jet and progenitor properties. We find that in all cases where the jet is not choked too deep within the star, the outflow carries a roughly constant amount of energy per logarithmic scale of proper velocity over a wide range of velocities, which depends mostly on the cocoon volume at the time of its breakout. This is a universal property of jets driven outflows, which does not exist in outflows of spherically symmetric explosions or when the jets are choked very deep within the star. We therefore conclude that jets that are choked (not too deep) provide a natural explanation to the fast material seen in the early spectra of stripped envelope SNe that are not associated with LGRBs, and that properties of this material could reveal information on the otherwise hidden jets.
The X-ray view of optically selected dual AGN
Authors: De Rosa Alessandra , Vignali Cristian , Severgnini Paola , Bianchi Stefano , Bogdanović Tamara , Charisi Maria , Guainazzi Matteo , Haiman Zoltan , Komossa S , Paragi Zsolt , Perez-Torres Miguel , Piconcelli Enrico , Ducci Lorenzo , Parvatikar Manali , Serafinelli Roberto
Published: December 2022

We present a study of optically selected dual Active Galactic Nuclei (AGN) with projected separations of 3–97 kpc. Using multiwavelength (MWL) information (optical, X-ray, mid-IR), we characterized the intrinsic nuclear properties of this sample and compared them with those of isolated systems. Among the 124 X-ray-detected AGN candidates, 52 appear in pairs and 72 as single X-ray sources. Through MWL analysis, we confirmed the presence of the AGN in >80 per cent of the detected targets in pairs (42 out of 52). X-ray spectral analysis confirms the trend of increasing AGN luminosity with decreasing separation, suggesting that mergers may have contributed to triggering more luminous AGN. Through X-ray/mid-IR ratio versus X-ray colours, we estimated a fraction of Compton-thin AGN (with 1022 cm−2 < NH < 1024 cm−2) of about 80 per cent, while about 16 per cent are Compton-thick sources (with NH > 1024 cm−2). These fractions of obscured sources are larger than those found in samples of isolated AGN, confirming that pairs of AGN show higher obscuration. This trend is further confirmed by comparing the de-reddened [O iii] emission with the observed X-ray luminosity. However, the derived fraction of Compton-thick sources in this sample at the early stages of merging is lower than that reported for late-merging dual-AGN samples. Comparing NH from X-rays with that derived from E(B − V) from narrow-line regions, we found that the absorbing material is likely to be associated with the torus or broad-line regions. We also explored the X-ray detection efficiency of dual-AGN candidates, finding that, when observed properly (at on-axis positions and with long exposures), X-ray data represent a powerful way to confirm and investigate dual-AGN systems.
Gravitational waves from double white dwarfs as probes of the milky way
Authors: Georgousi Maria , Karnesis Nikolaos , Korol Valeriya , Pieroni Mauro , Stergioulas Nikolaos
Published: December 2022

Future gravitational wave detectors, such as the Laser Interferometer Space Antenna (LISA), will be able to resolve a significant number of the ultra compact stellar-mass binaries in our own Galaxy and its neighbourhood. These will be mostly double white dwarf (DWD) binaries, and their underlying population characteristics can be directly correlated to the different properties of the Galaxy. In particular with LISA, we will be able to resolve ${\sim}\mathcal {O}(10^4)$ binaries, while the rest will generate a confusion foreground signal. Analogously to how the total electromagnetic radiation emitted by a galaxy can be related to the underlying total stellar mass, in this work, we propose a framework to infer the same quantity by investigating the spectral shape and amplitude of the confusion foreground signal. For a fixed DWD evolution model and thus a fixed binary fraction, we retrieve percentage-level relative errors on the total stellar mass, which improves for increasing values of the mass. At the same time, we find that variations in the Milky Way shape at a fixed mass and at scale heights smaller than 500 pc are not distinguishable based on the shape of stochastic signal alone. We perform this analysis on simulations of the LISA data, estimating the resolvable sources based on signal-to-noise criteria. Finally, we utilize the catalogue of resolvable sources to probe the characteristics of the underlying population of DWD binaries. We show that the DWD frequency, coalescence time and chirp mass (up to <0.7 M⊙) distributions can be reconstructed from LISA data with no bias.
G-rich motifs within phosphorothioate-based antisense oligonucleotides (ASOs) drive activation of FXN expression through indirect effects
Authors: Wang Feng , Calvo-Roitberg Ezequiel , Rembetsy-Brown Julia M , Fang Minggang , Sousa Jacquelyn , Kartje Zachary J , Krishnamurthy Pranathi Meda , Lee Jonathan , Green Michael R , Pai Athma A , Watts Jonathan K
Published: December 2022

Friedreich’s ataxia is an incurable disease caused by frataxin (FXN) protein deficiency, which is mostly induced by GAA repeat expansion in intron 1 of the FXN gene. Here, we identified antisense oligonucleotides (ASOs), complementary to two regions within the first intron of FXN pre-mRNA, which could increase FXN mRNA by ∼2-fold in patient fibroblasts. The increase in FXN mRNA was confirmed by the identification of multiple overlapping FXN-activating ASOs at each region, two independent RNA quantification assays, and normalization by multiple housekeeping genes. Experiments on cells with the ASO-binding sites deleted indicate that the ASO-induced FXN activation was driven by indirect effects. RNA sequencing analyses showed that the two ASOs induced similar transcriptome-wide changes, which did not resemble the transcriptome of wild-type cells. This RNA-seq analysis did not identify directly base-paired off-target genes shared across ASOs. Mismatch studies identified two guanosine-rich motifs (CCGG and G4) within the ASOs that were required for FXN activation. The phosphorodiamidate morpholino oligomer analogs of our ASOs did not activate FXN, pointing to a PS-backbone-mediated effect. Our study demonstrates the importance of multiple, detailed control experiments and target validation in oligonucleotide studies employing novel mechanisms such as gene activation.
Efficacy of Continuous Intrathecal Infusion Trialing with a Mixture of Fentanyl and Bupivacaine in Chronic Low Back Pain Patients
Authors: Hayek Salim M , Jones Bradford A , Veizi Elias , Tran Thang Q , DeLozier Sarah J
Published: December 2022

Intrathecal trialing is used as a screening prognostic measure prior to intrathecal drug delivery system implant. The purpose of this study was to determine the efficacy of a continuous intrathecal infusion of an admixture of bupivacaine and fentanyl in patients with chronic low back pain.

Patients with refractory chronic low back pain in the setting of previous lumbar spine surgery and/or chronic vertebral compression fracture(s) were enrolled in a randomized double blind cross-over study comparing saline infusion to infusion of a solution containing bupivacaine combined with low-dose fentanyl over a 14–18 hour period. The primary outcome measure was the change in pain intensity at the end of the screening trial. Patients who experienced significant pain reduction from either infusion relative to baseline pain were offered a permanent implant.

In total, 36 patients were enrolled, with 31 patients trialed and 25 implanted. At the end of the screening trial, pain scores, at rest or with activity, decreased appreciably in both groups; however, significantly better improvements occurred in the fentanyl/bupivacaine group compared to saline both with activity and at rest (P = .016 and .006, respectively). Treatment order appeared to affect outcome with saline demonstrating a placebo response. At 12 months following implant, primary and secondary outcome measures continued to be significantly reduced from baseline.

Continuous intrathecal delivery of a combination of zlow-dose fentanyl with bupivacaine is superior to saline in screening intrathecal trialing for back pain reduction. With longer term delivery, a sustained reduction of chronic low back pain was also observed.
Early-Stage Phenotyping of Sweet Potato Virus Disease Caused by Sweet Potato Chlorotic Stunt Virus and Sweet Potato Virus C to Support Breeding
Authors: David Maria , Kante Moctar , Fuentes Segundo , Eyzaguirre Raul , Diaz Federico , De Boeck Bert , Mwanga Robert O. M. , Kreuze Jan , Grüneberg Wolfgang J.
Published: December 2022

Sweet potato virus disease (SPVD) is a global constraint to sweetpotato (Ipomoea batatas) production, especially under intensive cultivation in the humid tropics such as East Africa. The objectives of this study were to develop a precision SPVD phenotyping protocol, to find new SPVD-resistant genotypes, and to standardize the first stages of screening for SPVD resistance. The first part of the protocol was based on enzyme-linked immunosorbent assay results for sweet potato chlorotic stunt virus (SPCSV) and sweet potato virus C (SPVC) with adjustments to a negative control (uninfected clone Tanzania) and was performed on a prebreeding population (VZ08) comprising 455 clones and 27 check clones graft inoculated under screenhouse conditions. The second part included field studies with 52 selected clones for SPCSV resistance from VZ08 and 8 checks. In screenhouse conditions, the resistant and susceptible check clones performed as expected; 63 clones from VZ08 exhibited lower relative absorbance values for SPCSV and SPVC than inoculated check Tanzania. Field experiments confirmed SPVD resistance of several clones selected by relative absorbance values (nine resistant clones in two locations; that is, 17.3% of the screenhouse selection), supporting the reliability of our method for SPVD-resistance selection. Two clones were promising, exhibiting high storage root yields of 28.7 to 34.9 t ha−1 and SPVD resistance, based on the proposed selection procedure. This modified serological analysis for SPVD-resistance phenotyping might lead to more efficient development of resistant varieties by reducing costs and time at early stages, and provide solid data for marker-assisted selection with a quantitative tool for classifying resistance.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
“Time-In”: A Tool for Interrupting Bias in Medical School Admissions Committee Meetings
Authors: Parkas Valerie , Maysonet Jessica , Chudow Jacquelyn , Hess Leona , Swartz Talia H.
Published: December 2022

Problem

During high-stakes committee meetings, bias is often expressed but goes uninterrupted because there is no formal structure to interrupt it. Bias impacts decision making and can further disadvantage those from backgrounds that have been marginalized.

Approach

The MD and MD–PhD admissions committees at the Icahn School of Medicine at Mount Sinai in NY in the 2020–2021 admissions season introduced a “Time-In” tool to interrupt bias during committee meetings. This study aimed to evaluate the impact of implementing the “Time-In” tool on committee members’ perception of bias as a problem and the likelihood of committee members recognizing, reporting, discussing, and educating others about bias after implementation.

Outcomes

There were 117 responses to the pre- and postseason surveys. In aggregate, respondents reported a statistically significant reduction in the perception of bias in the admissions process from preseason to postseason. There was no change in the likelihood of committee members in aggregate endorsing comfort in recognizing, reporting, discussing, and educating about bias; however, notable gaps existed in the comfort of groups discussing bias publicly, i.e., respondents who are from backgrounds underrepresented in science and medicine, students, and new committee members were less comfortable than their comparators. By the postseason survey, these gaps were closed.

Next Steps

Implementing a “time-in” allows for interruption of bias, with an impact of reducing the perception of bias, empowering individuals, and reducing gaps among groups to discuss bias publicly. A “time-in” can profoundly impact decision-making bodies that are critical gatekeepers to the composition of the physician workforce. Future directions will focus on enhancing committee members’ skills in educating others about bias.
Rejecting Reforms, Yet Calling for Change: A Qualitative Analysis of Proposed Reforms to the Residency Application Process
Authors: Dacre Michael , Branzetti Jeremy , Hopson Laura R. , Regan Linda , Gisondi Michael A.
Published: December 2022

Purpose

Annual increases in the number of residency applications burden students and challenge programs. Several reforms to the application process have been proposed; however, stakeholder input is often overlooked. The authors examined key stakeholders’ opinions about several proposed reforms to the residency application process and identified important factors to guide future reforms.

Method

Using semistructured interviews, the authors asked educational administrators and trainees to consider 5 commonly proposed reforms to the residency application process: Match to obtain residency interviews, preference signaling, application limits, geographic preference disclosure, and abolishing the Match. The authors conducted a modified content analysis of interview transcripts using qualitative and quantitative analytic techniques. Frequency analysis regarding the acceptability of the 5 proposed reforms and thematic analysis of important factors to guide reform were performed. Fifteen-minute interviews were conducted between July and October 2019, with data analysis completed during a 6-month period in 2020 and 2021.

Results

Participants included 30 stakeholders from 9 medical specialties and 15 institutions. Most participants wanted to keep the Match process intact; however, they noted several important flaws in the system that disadvantage students and warrant change. Participants did not broadly support any of the 5 proposed reforms. Two themes were identified: principles to guide reform (fairness, transparency, equity, reducing costs to students, reducing total applications, reducing work for program directors, and avoiding unintended consequences) and unpopular reform proposals (concern that application limits threaten less competitive students and signaling adds bias to the system).

Conclusions

Key stakeholders in the residency application process believe the system has important flaws that demand reform. Despite this, the most commonly proposed reforms are unacceptable to these stakeholders because they threaten fairness to students and program workload. These findings call for a larger investigation of proposed reforms with a more nationally representative stakeholder cohort.
URINARY METABOLOMICS OF CENTRAL SEROUS CHORIORETINOPATHY
Authors: Meyerle Catherine B. , Lyu Pin , Qian Jiang , Freund K. Bailey , Hafiz Gulnar , Handa James T. , Semba Richard D.
Published: December 2022

Purpose:

To analyze the urinary metabolomic profile of central serous chorioretinopathy cases.

Methods:

In a cross-sectional study, 80 participants with central serous chorioretinopathy were compared with 80 age-matched and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4 platform.

Results:

Of 1,031 metabolites total that were measured in urine samples, 53 were upregulated and 27 downregulated in central serous chorioretinopathy participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid subpathway. The downregulated metabolites are unrelated to the identified corticosteroid subpathway.

Conclusion:

The upregulation of urinary tetrahydrocortisol sulfate in central serous chorioretinopathy cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.