bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking de facto autonomy? A multi‐policy area approach and the regulatory policy process
Authors: Coban M. Kerem
Published: December 2022

We examine de facto autonomy across regulatory agencies and policy sectors. Yet not much is known whether, how and why de facto autonomy could vary across policy areas within the same policy sector. This article demonstrates the existence of such variation and suggests that this variation depends on the interplay between stakeholders' diverging (or overlapping) policy preferences, deficient (or superior) organizational policy capacity, and institutional arrangements leading to enabled (or constrained) de facto autonomy. Relying on elite interviews and secondary resources, this study builds on an illustrative study on bank regulation in Turkey in the post‐GFC period and presents a nuanced understanding of de facto autonomy: a multi‐policy area approach to de facto autonomy that allows us to examine variation in de facto autonomy across policy areas, the determinants of the variation, and whether de facto autonomy is constrained or enabled, which structures the regulatory policy process.
Visual learning strategies for oral health promotion and treatment interventions in children and adolescents with hearing impairment – A systematic review
Authors: Shrivastava Richa , Gupta Arpit , Nishant  , Sharda Shweta , Das Diptajit , Goyal Ashima
Published: December 2022

Aim

People with hearing impairment (HI) prefer visual learning strategies in daily activities owing to their reliance on vision. The aim of this systematic review is to evaluate the effectiveness of visual learning as a communication strategy in improving oral hygiene and dental care of children and adolescents with HI.

Methods and Results

Four electronic databases were searched and complemented by hand searching for original intervention studies published till December 2021. Eligible studies were screened, data was extracted as per priori data collection form and analyzed by thematic content analysis. The quality of studies was assessed as per the validated tools appropriate for study designs including ROB2, ROBINS‐I, and NIH quality assessment tool. Out of 4159 records identified and 1302 duplicates removed, 24 original studies were identified and the visual learning strategies were classified into sign language, visual aids with or without sign language, customized educational demonstrations and the interim role of training the teachers. These strategies helped in improving oral hygiene status, oral health‐related knowledge and attitude as well as dental anxiety during treatment. Participants were found to be satisfied with these strategies, however, significant heterogeneity in the included studies precluded meaningful meta‐analysis. ROB2 and ROBINS were rated as high and serious in all included trials, respectively, and NIH Quality Assessment Tool for Pre‐Post Studies With No Control as fair in five studies and poor in three.

Conclusion

Our findings emphasize the significance of visual learning, however, long‐term rigorously designed trials are needed to better understand effective and patient‐centered communication methods for people with HI.
The dark triad and subjective well‐being: The mediating role of cognitive‐emotional regulation strategies
Authors: Gómez‐Leal Raquel , Gutiérrez‐Cobo María J. , Megías‐Robles Alberto , Fernández‐Berrocal Pablo
Published: December 2022

The dark triad (DT) is composed of psychopathy, narcissism, and Machiavellianism. These traits have usually been correlated with maladaptive strategies of emotion regulation. In turn, these types of strategies have shown a negative relationship with the components of subjective well‐being (SWB): affective well‐being (AWB) and cognitive well‐being (CWB). The principal objective of the present study was to analyze the possible mediating role of adaptive and maladaptive cognitive‐emotional regulation strategies in the relationship between the DT and SWB components. For this purpose, a community sample of 678 participants (Mage = 35.03; 53.1% women) completed the Satisfaction with Life Scale (SWB), the Positive and Negative Affect Schedule (PANAS), the Cognitive Emotional Regulation Questionnaire (CERQ‐36), and the Short Dark Triad (SD‐3). The results showed a good fit with the model in which Machiavellianism was indirectly and negatively related to CWB through the effect of maladaptive strategies and AWB, and indirectly and positively related to CWB through the effect of adaptive strategies and AWB. Narcissism was indirectly positively related to CWB through the effect of adaptive strategies and AWB. Finally, psychopathy was indirectly negatively associated with CWB through the effect of adaptive strategies and AWB. Limitations and clinical implications of this research are discussed.
The physiology of ice hockey performance: An update
Authors: Vigh‐Larsen Jeppe F. , Mohr Magni
Published: December 2022

Ice hockey is an intense team sport characterized by repeated bursts of fast‐paced skating, rapid changes in speed and direction and frequent physical encounters. These are performed in on‐ice shifts of ~30–80 s interspersed with longer sequences of passive recovery, resulting in about 15–25 min on‐ice time per player. Nearly 50% of the distance is covered at high‐intensity skating speeds and with an accentuated intense activity pattern in forwards compared to defensemen. During ice hockey match‐play, both aerobic and anaerobic energy systems are significantly challenged, with the heart rate increasing toward maximum levels during each shift, and with great reliance on both glycolytic and phosphagen ATP provision. The high‐intensity activity pattern favors muscle glycogen as fuel, leading to pronounced reductions despite the relatively brief playing time, including severe depletion of a substantial proportion of individual fast‐ and slow‐twitch fibers. Player‐tracking suggests that the ability to perform high‐intensity skating is compromised in the final stages of a game, which is supported by post‐game reductions in repeated‐sprint ability. Muscle glycogen degradation, in particular in individual fibers, as well as potential dehydration and hyperthermia, may be prime candidates implicated in exacerbated fatigue during the final stages of a game, whereas multiple factors likely interact to impair exercise tolerance during each shift. This includes pronounced PCr degradation, with potential inadequate resynthesis in a proportion of fast‐twitch fibers in situations of repeated intense actions. Finally, the recovery pattern is inadequately described, but seems less long‐lasting than in other team sports.
Crop rotation with plastic mulching increased soil organic carbon and water sustainability: A field trial on the Loess Plateau
Authors: Zhang Xucheng , Hou Huizhi , Yin Jiade , Fang Yanjie , Yu Xianfeng , Wang Hongli , Ma Yifan , Lei Kangning
Published: December 2022

Appropriate crop rotations are beneficial for food security and carbon sequestration. In cool and semiarid rain‐fed areas, however, the effect on carbon sequestration in soil and the soil–crop system is not clear. In this study, a crop rotation field experiment was carried out on the Loess Plateau, China, involving (1) wheat continuous cropping (WCC), (2) maize continuous cropping (MCC), (3) potato continuous cropping (PCC) and (4) wheat–maize–potato rotating cropping (RC). All treatments were tilled once, and then, plastic mulched immediately to inhibit evaporation. We found that the rotating cropping system improved water storage in the 0–300 cm soil profile by 65.8 mm through the 6 years, while MCC depleted deep soil moisture. In a drought year, total dry matter (DM) for the rotating cropping was greater by 23.9% and 79.3% and harvested carbon quantity (HCQ) by 0.6 and 1.8 Mg ha−1 compared with WCC and MCC systems, respectively. Total evapotranspiration significantly decreased by 14.5% compared with MCC, with no significant change compared with WCC and PCC. The soil organic carbon (SOC) concentration at 20–30 cm depth in the rotating cropping system was 36.0%, 28.0% and 30.3% greater than those of WCC, MCC and PCC, respectively. Similarly, the SOC sequestration rate at this depth was higher by 3.8, 3.2 and 3.4 Mg ha−1, respectively. The pure carbon accumulation (PCA) of the rotating cropping system significantly increased compared with WCC and PCC, resulting in increased water use efficiency of pure carbon accumulation (WCP) by 11.1, 2.2 and 3.1 Mg ha−1 mm−1 compared with the WCC, MCC and PCC systems, respectively. Overall, the rotating cropping (RC) system maintained better soil water conditions, sustained crop development and SOC sequestration, especially optimizing the relationship between crop water utilization and SOC sequestration in soil–crop system in the cool semiarid rain‐fed area.
Evaluation of hypochlorous acid as an ear flush in dogs with chronic otitis externa
Authors: Mueller Ralf S. , Baumann Katja N. , Boehm Teresa , Dörfelt Stefanie , Kasper Bettina , Udraite‐Vovk Laura
Published: December 2022

Background

Chronic otitis externa (OE) in dogs frequently requires anaesthetised ear flushing.

Objectives

To evaluate hypochlorous acid as an ear flushing and antimicrobial agent in dogs with chronic OE.

Animals

Twenty dogs with chronic OE caused by the same organisms bilaterally.

Materials and Methods

One ear was flushed under anaesthesia with hypochlorous acid, the other with saline solution. Subsequently, the ear flushed with hypochlorous acid was cleaned with the same solution twice daily for 2 weeks, the other ear with a commercial ear cleaner. An ear medication containing miconazole, polymyxin B and prednisolone was used once daily in both ears. Clinical scores were determined before the flush. Ear cytological results were obtained, a hearing test was conducted before and after the ear flush, and a culture was taken directly after flushing. Ears were evaluated after 2 weeks of therapy.

Results

Yeast was present in the ears of 11, cocci in one and a mixed infection in eight dogs. Five ears were negative on culture after flushing with hypochlorous acid, one after the saline flush. Clinical and cytological scores decreased significantly with both solutions after 2 weeks of treatment. There was no difference between treatments in any of the scores at any time point between treatments and in the results of the hearing test before and after the flushing procedure. Adverse effects were not seen.

Conclusions and Clinical Relevance

Hypochlorous acid is a suitable cleaning solution for canine OE.
Clinical ophthalmic parameters of the Quaker parrot (Myiopsitta monachus)
Authors: Halsmer Emily L. , Heatley Jennifer Jill , Scott Erin M.
Published: December 2022

Purpose

Ophthalmic diagnosis in many avian species remains hindered by a lack of normative values. This study aimed to establish normal ophthalmic parameters for select diagnostic tests in clinically normal Quaker parrots.

Methods

Ninety‐six captive Quaker parrots aged 8–18 years underwent ophthalmic examination to include assessment of neuro‐ophthalmic reflexes, phenol red thread test, rebound tonometry, fluorescein staining, palpebral fissure length measurements, slit lamp biomicroscopy, indirect ophthalmoscopy, and ocular ultrasound biometry.

Results

Menace response, dazzle reflex, and direct pupillary light reflex were present for all Quaker parrots. Tear production (mean ± SD) was 13.3 ± 4.0 mm/15 s and intraocular pressure (IOP, mean ± SD) was 10.6 ± 1.4 and 6.0 ± 1.3 mmHg in the D and P rebound tonometer calibration settings, respectively. For IOP measurement, D and P calibration settings were not interchangeable, with the lesser variation of the D setting preferred in the absence of a gold standard. Ultrasound measurement of the anterior chamber depth increased with age and males had longer axial globe and vitreous lengths. Incidental adnexal and ocular lesions, identified in 36/96 (37.5%) of Quaker parrots, did not statistically affect the created reference data.

Conclusions

This work provides reference values and clinical findings to assist with monitoring the health of wild populations and maintaining the health of captive Quaker parrots.
ANALYSIS OF BUILDING DEFECTS AT RESIDENTIAL COLLEGES: A CASE STUDY AT HIGHER EDUCATION FACILITIES
Authors: Dzulkifli Nur'afini , Sarbini Noor Nabilah , Abidin Nur IzieAdiana , Ibrahim Izni Syahrizal
Published: December 2022

Residential colleges are where students spend a significant amount of time at university. The university’s maintenance team must keep the building facilities in good condition to ensure the safety and comfort of the students and staff as well as to protect the university’s reputation. However, with today’s economic challenges, management frequently encounters difficulties in maintaining the buildings, resulting in the high number of complaints from building users. As a result, early detection of complaint trends is critical in reducing issues. Based on user complaints and the ‘learning from failure’ philosophy, the main aim of this study is to identify the most common complaint of building defects in residential colleges. The scope of the study is limited to 9 residential colleges from one (1) Malaysian public university. Complaints from 2012 to 2017 due to defects were categorized into 3 main areas of civil, electrical and mechanical. From here, the most frequent complaints from these categories were then identified. From the findings of this study, defects under civil received the highest number of complaints (62%), followed by defects under electrical (35%) and mechanical (3%). Under the category of civil, most defects were reported due to damage component, leaking and clogging. The solutions emphasize the importance of quality control, on improving workmanship, increasing building occupants’ awareness level, and improving complaints management. Overall, this study is significant when constructing new buildings because it provides information to the operation team as early as the design stage to consider the possibility of future maintenance activities, and planning improvement.
Inhibitory interneurons show early dysfunction in a SOD1 mouse model of amyotrophic lateral sclerosis
Authors: Cavarsan Clarissa F. , Steele Preston R. , Genry Landon T. , Reedich Emily J. , McCane Lynn M. , LaPre Kay J. , Puritz Alyssa C. , Manuel Marin , Katenka Natallia , Quinlan Katharina A.
Published: December 2022

Few studies in amyotrophic lateral sclerosis (ALS) measure effects of the disease on inhibitory interneurons synapsing onto motoneurons (MNs). However, inhibitory interneurons could contribute to dysfunction, particularly if altered before MN neuropathology, and establish a long‐term imbalance of inhibition/excitation. We directly assessed excitability and morphology of glycinergic (GlyT2 expressing) ventral lumbar interneurons from SOD1G93AGlyT2eGFP (SOD1) and wild‐type GlyT2eGFP (WT) mice on postnatal days 6–10. Patch clamp revealed dampened excitability in SOD1 interneurons, including depolarized persistent inward currents (PICs), increased voltage and current threshold for firing action potentials, along with a marginal decrease in afterhyperpolarization duration. Primary neurites of ventral SOD1 inhibitory interneurons were larger in volume and surface area than WT. GlyT2 interneurons were then divided into three subgroups based on location: (1) interneurons within 100 μm of the ventral white matter, where Renshaw cells (RCs) are located, (2) interneurons interspersed with MNs in lamina IX, and (3) interneurons in the intermediate ventral area including laminae VII and VIII. Ventral interneurons in the RC area were the most profoundly affected, exhibiting more depolarized PICs and larger primary neurites. Interneurons in lamina IX had depolarized PIC onset. In lamina VII–VIII, interneurons were least affected. In summary, inhibitory interneurons show very early region‐specific perturbations poised to impact excitatory/inhibitory balance of MNs, modify motor output and provide early biomarkers of ALS. Therapeutics like riluzole that universally reduce CNS excitability could exacerbate the inhibitory dysfunction described here.

image

Key points

Spinal inhibitory interneurons could contribute to amyotrophic lateral sclerosis (ALS) pathology, but their excitability has never been directly measured.

We studied the excitability and morphology of glycinergic interneurons in early postnatal transgenic mice (SOD1G93AGlyT2eGFP).

Interneurons were less excitable and had marginally smaller somas but larger primary neurites in SOD1 mice.

GlyT2 interneurons were analysed according to their localization within the ventral spinal cord. Interestingly, the greatest differences were observed in the most ventrally located interneurons.

We conclude that inhibitory interneurons show presymptomatic changes that may contribute to excitatory/inhibitory imbalance in ALS.
Boiler Embrittlement
Authors: Zapffe C. A.
Published: December 2022

In the introductory section of this paper, boiler embrittlement as a field of study is traced back toward the very invention and genesis of steam boilers. The study is traced through the miscellaneous researches of several countries up to the establishment of unified research in three institutions: Britain’s National Physical Laboratory in 1917, America’s University of Illinois in 1917, and Germany’s Vereinigung der Grosskesselbesitzern in 1920.

In the second part of the paper, the chronological study is extended to date, but with emphasis on a critical evaluation of all published work which can be found from America, England, Germany, France, Sweden, Italy, and Russia. The roles of stress, caustic, chemical attack, “aging,” and hydrogen are given especial attention along with all other possible factors in boiler embrittlement. These factors are then shown to be identical with those observed in the attack of steel by hydrogen at elevated temperatures, a subject given peculiar neglect in the literature on boiler embrittlement.

In the concluding section, the various factors involved in boiler embrittlement are interpreted from the viewpoint that “boiler embrittlement” is nothing other than an intermediate stage in a naturally occurring hydrogen-purification process. The arguments which have revolved around intercrystalline and transcrystalline paths of the fracture, the behavior of inhibitors and accelerators, the prerequisition of stress and of caustic, and the role played by the steel are discussed to show how logically all observations resolve themselves in the light of this new conception. This interpretation for boiler embrittlement is then corroborated visually by simple experiments made directly upon specimens from boiler plate which exhibited “boiler embrittlement.” Plans for future research along entirely new lines are suggested.
Ratio and Multiple-Fuel Controls in the Steel Industry
Authors: Ziebolz Herbert
Published: December 2022

The need for accurate control of the furnace atmosphere in the steel industry has brought about the development of a variety of designs and basic circuits to solve this problem. The methods used and the apparatus which were developed are briefly discussed, i.e., (1) the basic ratio control, (2) the control mixing stations, and (3) the controls available for burning several fuels simultaneously with only one common supply for combustion air.
New Machines for Creep and Creep-Rupture Tests
Authors: Manjoine M. J.
Published: December 2022

This paper describes two new creep-rupture machines. One combines eight conventional lever-arm creep machines into a single unit but with individual furnaces, controls, and recording equipment. The elongation of each test specimen is indicated by a revolution counter and can be read directly. The indicating counters for the eight specimens are brought to a single panel and photographed periodically to obtain a continuous record of the creep. The counters are driven by new extensometers which are attached to the test specimens. Two types of extensometers are used; one which gives readings over a 3-in. gage length in hundred thousandths of an inch for measuring small strains up to 2 per cent total strain, and a second extensometer which records in ten-thousandths inch for strains up to rupture. The second is a screw-driven creep-rupture machine in which the specimen is loaded through a stiff spring. A continuous elongation-time curve up to rupture is automatically recorded without the need of an extensometer on the test specimen. The machine has a capacity of 10 tons and occupies a floor space of only 15 × 15 in. It can also be used to make short-time tensile, constant-strain-rate, and relaxation tests. The latter test requires the use of an extensometer on the gage length of the test specimen. To illustrate the satisfactory operation of these machines, the results of creep-to-rupture tests on a cast 25 Cr 12 Ni alloy are presented. The data from these tests are summarized in “design curves” which serve to describe the behavior of a material at a given temperature.
Properties and Development of Papreg—A High-Strength Laminated Paper Plastic
Authors: Erickson E. C. O. , Mackin G. E.
Published: December 2022

Papreg the new paper-base laminate which has recently found application in aircraft and other strength structures resulted from research at the Forest Products Laboratory. Having more than twice the tensile strength and improved mechanical properties compared with the best earlier paper-base laminates, papreg also lends itself to low-pressure molding techniques and can be formed to moderate double curvature without special treatment. This paper reviews the development work, the characteristics, properties, and service experience with papreg.
Stress-Rupture Characteristics of Various Steels in Steam at 1200 F
Authors: Agnew J. T. , Hawkins G. A. , Solberg H. L.
Published: December 2022

Small tensile specimens made from low-carbon, carbon-moly, 2¼ Cr-1 Mo, 5 Cr-Mo-Si, 9 Cr-Mo-Si, 12 Cr, 18 Cr-8 Ni, 25 Cr-20 Ni, and 5 Cr-Mo-Ti steels were placed in a steam reaction chamber at 1200 F and stressed in tension for periods of time ranging from 10 hr to 7700 hr. Data were taken on time to rupture, elongation, reduction in area, depth of scale layer, effect of type of flow, and type and angle of fracture. A photomicrographic study was made of the ruptured specimens. The straight-line relationship between stress and time to rupture on log-log co-ordinates postulated by White, Clark, and Wilson for tests in air also holds for tests in steam.
Precision Tachometer for Use in Wind-Tunnel Testing
Authors: Fairley R. K. , Clark H. L.
Published: December 2022

The equipment described is a high-speed high-accuracy tachometer developed primarily to measure rotative speed during the power-testing of airplane models in wind tunnels by measuring the frequency of a tachometer generator. The frequency being measured is automatically compared with that of a tuning fork and indicated on an instrument having a scale length of 86 in.
Tactile perception of auditory roughness
Authors: Bernard Corentin , Kronland-Martinet Richard , Fery Madeline , Ystad Sølvi , Thoret Etienne
Published: December 2022

Auditory roughness resulting from fast temporal beatings is often studied by summing two pure tones with close frequencies. Interestingly, the tactile counterpart of auditory roughness can be provided through touch with vibrotactile actuators. However, whether auditory roughness could also be perceived through touch and whether it exhibits similar characteristics are unclear. Here, auditory roughness perception and its tactile counterpart were evaluated using pairs of pure tone stimuli. Results revealed similar roughness curves in both modalities, suggesting similar sensory processing. This study attests to the relevance of such a paradigm for investigating auditory and tactile roughness in a multisensory fashion.
Multivalent state transitions shape the intratumoral composition of small cell lung carcinoma
Authors: Gopal Priyanka , Petty Aaron , Rogacki Kevin , Bera Titas , Bareja Rohan , Peacock Craig D. , Abazeed Mohamed E.
Published: December 2022

Studies to date have not resolved how diverse transcriptional programs contribute to the intratumoral heterogeneity of small cell lung carcinoma (SCLC), an aggressive tumor associated with a dismal prognosis. Here, we identify distinct and commutable transcriptional states that confer discrete functional attributes in individual SCLC tumors. We combine an integrative approach comprising the transcriptomes of 52,975 single cells, high-resolution measurement of cell state dynamics at the single-cell level, and functional and correlative studies using treatment naïve xenografts with associated clinical outcomes. We show that individual SCLC tumors contain distinctive proportions of stable cellular states that are governed by bidirectional cell state transitions. Using drugs that target the epigenome, we reconfigure tumor state composition in part by altering individual state transition rates. Our results reveal new insights into how single-cell transition behaviors promote cell state equilibrium in SCLC and suggest that facile plasticity underlies its resistance to therapy and lethality.
Arf GTPase activates the WAVE regulatory complex through a distinct binding site
Authors: Yang Sheng , Tang Yubo , Liu Yijun , Brown Abbigale J. , Schaks Matthias , Ding Bojian , Kramer Daniel A. , Mietkowska Magdalena , Ding Li , Alekhina Olga , Billadeau Daniel D. , Chowdhury Saikat , Wang Junmei , Rottner Klemens , Chen Baoyu
Published: December 2022

Cross-talk between Rho- and Arf-family guanosine triphosphatases (GTPases) plays an important role in linking the actin cytoskeleton to membrane protrusions, organelle morphology, and vesicle trafficking. The central actin regulator, WAVE regulatory complex (WRC), integrates Rac1 (a Rho-family GTPase) and Arf signaling to promote Arp2/3-mediated actin polymerization in many processes, but how WRC senses Arf signaling is unknown. Here, we have reconstituted a direct interaction between Arf and WRC. This interaction is greatly enhanced by Rac1 binding to the D site of WRC. Arf1 binds to a previously unidentified, conserved surface on the Sra1 subunit of WRC, which, in turn, drives WRC activation using a mechanism distinct from that of Rac1. Mutating the Arf binding site abolishes Arf1-WRC interaction, disrupts Arf1-mediated WRC activation, and impairs lamellipodia formation and cell migration. This work uncovers a new mechanism underlying WRC activation and provides a mechanistic foundation for studying how WRC-mediated actin polymerization links Arf and Rac signaling in cells.
Programmable aniso-electrodeposited modular hydrogel microrobots
Authors: Zheng Zhiqiang , Wang Huaping , Demir Sinan Ozgun , Huang Qiang , Fukuda Toshio , Sitti Metin
Published: December 2022

Systems with programmable and complex shape morphing are highly desired in many fields wherein sensing, actuation, and manipulation must be performed. Living organisms use nonuniform distributions of their body structural composition to achieve diverse shape morphing, motion, and functionality. However, for the microrobot fabrication, these designs often involve complicated robotic architectures requiring time-consuming and arduous fabrication processes. This paper proposes a single-step aniso-electrodeposition method for fabricating modular microrobots (MMRs) with distinct functions in each modular segment. By programming the electric field, the microscale stripe-shaped structure can be endowed with diverse shape-morphing capabilities, such as spiraling, twisting, bending, and coiling. The proposed fabrication method can develop MMRs with multiple independent modules onto which cells, drugs, and magnetic nanoparticles can be loaded to achieve multifunctionality. Thus, MMRs can perform multiple tasks, such as propulsion, grasping, and object delivery, simultaneously under magnetic control and ionic and pH stimuli.
Multidimensional control of therapeutic human cell function with synthetic gene circuits
Authors: Li Hui-Shan , Israni Divya V. , Gagnon Keith A. , Gan Kok Ann , Raymond Michael H. , Sander Jeffry D. , Roybal Kole T. , Joung J. Keith , Wong Wilson W. , Khalil Ahmad S.
Published: December 2022

Synthetic gene circuits that precisely control human cell function could expand the capabilities of gene- and cell-based therapies. However, platforms for developing circuits in primary human cells that drive robust functional changes in vivo and have compositions suitable for clinical use are lacking. Here, we developed synthetic zinc finger transcription regulators (synZiFTRs), which are compact and based largely on human-derived proteins. As a proof of principle, we engineered gene switches and circuits that allow precise, user-defined control over therapeutically relevant genes in primary T cells using orthogonal, US Food and Drug Administration–approved small-molecule inducers. Our circuits can instruct T cells to sequentially activate multiple cellular programs such as proliferation and antitumor activity to drive synergistic therapeutic responses. This platform should accelerate the development and clinical translation of synthetic gene circuits in diverse human cell types and contexts.
Structure of monkeypox virus DNA polymerase holoenzyme
Authors: Peng Qi , Xie Yufeng , Kuai Lu , Wang Han , Qi Jianxun , Gao George F. , Shi Yi
Published: December 2022

The World Health Organization declared mpox (or monkeypox) a public health emergency of international concern in July 2022, and prophylactic and therapeutic measures are in urgent need. The monkeypox virus (MPXV) has its own DNA polymerase F8, together with the processive cofactors A22 and E4, constituting the polymerase holoenzyme for genome replication. Here, we determined the holoenzyme structure in complex with DNA using cryo–electron microscopy at the global resolution of ~2.8 angstroms. The holoenzyme possesses an architecture that suggests a “forward sliding clamp” processivity mechanism for viral DNA replication. MPXV polymerase has a DNA binding mode similar to that of other B-family DNA polymerases from different species. These findings reveal the mechanism of the MPXV genome replication and may guide the development of anti-poxvirus drugs.
Agile and versatile climbing on ferromagnetic surfaces with a quadrupedal robot
Authors: Hong Seungwoo , Um Yong , Park Jaejun , Park Hae-Won
Published: December 2022

A climbing robot that can rapidly move on diverse surfaces such as floors, walls, and ceilings will have an enlarged operational workspace compared with other terrestrial robots. However, the climbing skill of robots in such environments has been limited to low speeds or simple locomotion tasks. Here, we present an untethered quadrupedal climbing robot called MARVEL (magnetically adhesive robot for versatile and expeditious locomotion), capable of agile and versatile climbing locomotion in ferromagnetic environments. MARVEL excels over prior climbing robots in terms of climbing speed and ability to execute various motions. It demonstrates the fastest vertical and inverted walking speed, whereas its versatile locomotion ability enables the highest number of gaits and locomotion tasks. The key innovations are an integrated foot design using electropermanent magnets and magnetorheological elastomers that provide large adhesion and traction forces, torque control actuators, and a model predictive control framework adapted for stable climbing. In experiments, the robot achieved locomotion on ceilings and vertical walls up to 0.5 meter (1.51 body lengths) per second and 0.7 meter (2.12 body lengths) per second, respectively. Furthermore, the robot exhibited complex behaviors such as stepping over 10-centimeter-wide gaps; overcoming 5-centimeter-high obstacles; and making transitions between floors, walls, and ceilings. We also show that MARVEL could climb on a curved surface of a storage tank covered with up to 0.3-millimeter-thick paint with rust and dust.
Genetic Determinants of Escherichia coli Survival in Beach Sand
Authors: Rumball Natalie A. , Alm Elizabeth W. , McLellan Sandra L.
Published: December 2022

Escherichia coli
is commonly used as an indicator of recent fecal pollution in recreational water despite its known ability to survive in secondary environments, such as beach sand. These long-term survivors from sand reservoirs can be introduced into the water column through wave action or runoff during precipitation events, thereby impacting the perception of local water quality.
Genome Sequence of Basidiomycetous Yeast Mrakia gelida MGH-2, Isolated from Skarvsnes Ice-Free Area, East Antarctica
Authors: Tsuji Masaharu , Ishihara Jun-ichi , Toyoda Atsushi , Takahashi Hiroki , Kudoh Sakae
Published: December 2022

Basidiomycetous yeast
Mrakia gelida
MGH-2 has been reported from Surikogi Ike in the Skarvsnes ice-free area, East Antarctica. Here, we report on the high-quality genome sequence of the
Mrakia gelida
MGH-2 strain analyzed by PacBio Sequel and HiSeq 2500 instruments.
Functional Characterization of 15 Novel Dense Granule Proteins in Toxoplasma gondii Using the CRISPR-Cas9 System
Authors: Zheng Xiao-Nan , Wang Jin-Lei , Elsheikha Hany M. , Wang Meng , Zhang Zhi-Wei , Sun Li-Xiu , Wang Xin-Cheng , Zhu Xing-Quan , Li Ting-Ting
Published: December 2022

Dense granule proteins (GRAs) play important roles in
Toxoplasma gondii
pathogenicity. However, the functions of many putative GRAs have not been elucidated.
Permian−Middle Triassic floral succession in North China and implications for the great transition of continental ecosystems
Authors: Shu Wenchao , Tong Jinnan , Yu Jianxin , Hilton Jason , Benton Michael J. , Shi Xiao , Diez José B. , Wignall Paul B. , Chu Daoliang , Tian Li , Yi Zhixing , Mao Yongdong
Published: December 2022

The global pattern of plant evolution through the Permian−Triassic mass extinction is uncertain, and the extent to which land plants were affected is debated. Detailed studies undertaken at a regional scale can help evaluate this floral transition, and thus we provide a detailed account of floral evolution from the Permian to Middle Triassic of North China based on new paleobotanical data and a refined biostratigraphy. Five floral transition events are identified from before, during, and after the Permian−Triassic crisis, including the disappearance of the gigantopterid flora (associated with loss of coal deposits), the end-Permian mass extinction of Paleophytic taxa, and gradual recovery in the Triassic with the stepwise appearance of the Mesophytic vegetation. The record begins with a Cisuralian gigantopterid-dominated rainforest community, and then a Lopingian walchian Voltziales conifer-ginkgophyte community that evolved into a voltzialean conifer-pteridosperm forest community. The last is associated with a change amongst terrestrial vertebrates from the Jiyuan fauna to a pareiasaur-dominated fauna, found in red beds that lack coal deposits due to arid conditions. The disappearance of the voltzialean conifer forest community may represents the end-Permian mass extinction of plants although it could also be a consequence of the non-preservation of plants in sedimentary red-beds. The first post-crisis plants are an Induan herbaceous lycopsid community, succeeded by the Pleuromeia-Neocalamites shrub marsh community. A pteridosperm shrub woodland community dominated for a short time in the late Early Triassic along with the reappearance of insect herbivory. Finally, in the Middle Triassic, gymnosperm forest communities gradually rose to dominance in both uplands and lowlands along with other diverse plant communities, indicating the establishment of the Mesophytic Flora.
Ocular surface squamous neoplasia in a patient following oral steroids for contralateral necrotising scleritis
Authors: Yin Grace , Gendler Shai , Teichman Joshua
Published: December 2022

A male patient in his 70s presented with left eye necrotising scleritis. His ocular history was significant for pterygium excision with mitomycin C 3 months prior in the affected eye, open-angle glaucoma, nuclear sclerosis cataract and previous sixth cranial nerve palsy. Scleral culture was negative and blood work was positive for rheumatoid factor and HLA-B27. The patient was treated for necrotising scleritis with oral doxycycline, vitamin C, ranitidine and prednisone with gradual taper over 45 days. Two months after initiating treatment, his necrotising scleritis achieved complete resolution; however, a new-onset ocular surface squamous neoplasia (OSSN) was identified at the temporal limbus of the contralateral eye. He was treated with topical interferon alpha-2b 1 million IU qid and achieved complete resolution after 4 months. The case highlights both the acute precipitation of OSSN following oral steroids and a sight-threatening complication following pterygium excision.
Healthy diets, lifestyle changes and well-being during and after lockdown: longitudinal evidence from the West Midlands
Authors: van Rens Thijs , Hanson Petra , Oyebode Oyinlola , Walasek Lukasz , Barber Thomas M , Al-Khudairy Lena
Published: December 2022

Background

‘Lockdowns’ to control the spread of COVID-19 in the UK affected many aspects of life and may have adversely affected diets. We aimed to examine (1) the effect of lockdowns on fruit and vegetable consumption, as a proxy for healthy diets more generally, and on weight and well-being, (2) whether any subgroup was particularly affected and (3) the barriers and facilitators to a healthy diet in lockdown.

Methods

We conducted a mixed-method longitudinal study, involving an online survey of 1003 adults in the West Midlands, UK, 494 of whom were surveyed at two different points in time. Our first time point was during stringent COVID-19 lockdown and the second during a period of more relaxed restrictions. We asked quantitative questions about fruit and vegetable consumption; physical activity, sociodemographic characteristics, body mass index and well-being and qualitative questions about the reasons behind reported changes.

Results

We find no evidence for decreased fruit and vegetable consumption during lockdown compared with afterwards. If anything, consumption increased by half a portion daily among women, particularly among those who normally have a long commute. This finding, combined with a significant increase in physical activity, suggests that behaviours were healthier during lockdown, consistent with higher self-reported health. However, well-being deteriorated markedly, and participants reported being heavier during the lockdown as well. Our qualitative data suggest that an abundance of resources (more time) supported higher fruit and vegetable consumption during lockdown, despite increased access issues.

Conclusions

Our results may assuage concerns that lockdowns adversely affected diets. They may point to the impact of commuting on diet, particularly for women. We add longitudinal evidence to a growing body of literature on the adverse effect of lockdown on mental health.
Steroid-sparing effect of ciclosporin A 1 mg/mL: 5-year case series of 107 children and young people with vernal keratoconjunctivitis
Authors: Dahlmann-Noor Annegret Hella , Roberts Clare , Muthusamy Kirithika , Calder Virginia , Hingorani Melanie
Published: December 2022

Background/aims

To explore the steroid-sparing and other therapeutic effects of ciclosporin A (CsA) 1 mg/mL in the management of vernal keratoconjunctivitis (VKC).

Methods

Open retrospective single-group interventional consecutive cohort study (case series) of 107 children and young people (CYP) age 4.4–18 years with severe and/or recurrent VKC who were prescribed CsA 1 mg/mL between November 2015 and May 2021 at one institution. Review of electronic patient records, noting clinical indication for prescribing CsA 1 mg/mL, dosage prescribed at initiation and follow-up, impact on steroid usage before and after commencing CsA as well as adverse events and indications for discontinuation of treatment.

Results

The median number of inflammatory episodes requiring treatment with topical corticosteroids fell from 3 (IQR 2–4) during the 12 months prior to CsA 1 mg/mL to 1 (IQR 0–3) during the 12 months after, excluding steroid prescriptions with the first CsA 1 mg/mL prescription (Wilcoxon signed ranks test, two tailed, p<0.01). In the 12-month period following initiation of CsA 1 mg/mL with concomitant prescription of topical corticosteroids (n=82), daily dosage of steroids was reduced in 79 (96.3%) and discontinued in 67 (81.7%). The median number of hospital clinic visits fell from 4 (IQR 3–5) to 3 (IQR 2–5) (Wilcoxon p<0.01). Adverse events leading to discontinuation of CsA 1 mg/mL within 12 months of starting included stinging (instillation site pain) (6/107, 5.6%) and skinrash (1/107, 0.9%).

Conclusion

Commercial preparations of CsA 1 mg/mL, licensed for severe VKC in CYP, significantly reduce the need for concomitant topical corticosteroids and hospital clinic visits. Adverse events which may lead to discontinuation are stinging and skin rash.
Survival and neurodevelopmental impairment of outborn preterm infants at 5.5 years of age: an EPIPAGE-2 prospective, matched study using multiple imputation
Authors: Jones Peter , Marchand-Martin Laetitia , Desplanches Thomas , Diguisto Caroline , Fresson Jeanne , Goffinet François , Dauger Stéphane , Ancel Pierre-Yves , Morgan Andrei Scott
Published: December 2022

Objective

To determine whether birth outside a level-3 centre (outborn) is associated with a difference in the combined outcome of mortality or moderate-to-severe neurological impairment at 5.5 years of age compared with birth in a level-3 centre (inborn) when antenatal steroids and gestational age (GA) are accounted for.

Design

Individual matched study nested within a prospective cohort. Each outborn infant was matched using GA and antenatal steroids with a maximum of four inborns. Conditional logistic regression was used to calculate ORs before being adjusted using maternal and birth characteristics. Analyses were carried out after multiple imputation for missing data.

Setting

EPIPAGE-2 French national prospective cohort including births up to 34 weeks GA inclusive.

Patients

Outborn and inborn control infants selected between 24 and 31 weeks GA were followed in the neonatal period and to 2 and 5.5 years. 3335 infants were eligible of whom all 498 outborns and 1235 inborn infants were included—equivalent to 2.5 inborns for each outborn.

Main outcome measure

Survival without moderate-to-severe neurodevelopmental impairment at 5.5 years.

Results

Chorioamnionitis, pre-eclampsia, caesarian birth and small-for-dates were more frequent among inborns, and spontaneous labour and antepartum haemorrhage among outborns. There was no difference in the main outcome measure at 5.5 years of age (adjusted OR 1.09, 95% CI 0.82 to 1.44); sensitivity analyses suggested improved outcomes at lower GAs for inborns.

Conclusion

In this GA and steroid matched cohort, there was no difference in survival without moderate-to-severe neurodevelopmental impairment to 5.5 years of age between inborn and outborn very preterm children. This suggests steroids might be important in determining outcomes.
Molecular signatures of intrarenal complement receptorsC3AR1andC5AR1correlate with renal outcome in human lupus nephritis
Authors: Tampe Désirée , Hakroush Samy , Tampe Björn
Published: December 2022

Objective

Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of kidney failure in patients with SLE, attributed to increased morbidity and mortality. The in situ deposition of intrarenal immune complexes promotes the accumulation of inflammatory cells and causes kidney injury.

Methods

We here extracted transcriptome array datasets for expression of complement molecules in human lupus nephritis. Furthermore, we performed gene set enrichment analysis to identify molecular signatures associated with follow-up kidney function in lupus nephritis.

Results

Within the glomerular compartment, intrarenal mRNA expression levels ofC3AR1(p=0.0333) andC5AR1(p=0.0167) correlated with treatment success reflected by kidney function recovery specifically in class III lupus nephritis, while no such association was observed in class II or class IV lupus nephritis. Interestingly, mRNA expression levels of either glomerularC3AR1orC5AR1resulted in identical gene set and signalling pathways enrichments in human lupus nephritis, including interferon signalling and signalling by interleukins. Direct comparison ofC3AR1andC5AR1confirmed a strong association between glomerular mRNA expression levels of both complement receptors (r=0.8955, p<0.0001).

Conclusions

This study provides additional insights into signalling pathways associated with intrarenal synthesis of complement components in lupus nephritis that might be also affected by targeted therapy of the complement system. These results require confirmation but may contribute to a personalised treatment approach in distinct classes of human lupus nephritis.
Significance of structural changes in the axial skeleton in patients with axial spondyloarthritis: how important are lesions in the sacroiliac joint?
Authors: Braun Juergen
Published: December 2022

Inflammatory back pain (IBP) is a characteristic clinical symptom of patients with axial spondyloarthritis (axSpA) that is caused by inflammation in the axial skeleton. In early disease stages the sacroiliac joints (SIJ) are most often affected, the spine usually at later stages. In many but clearly not all cases of axSpA new bone formation in form of syndesmophytes and ankylosis occur in the further course of the disease. Function and mobility may be impaired by both, inflammation and structural changes. In clinical trials outcome parameters most often used refer to pain, disease activity, function, mobility and global health but many researchers are also interested in radiographic progression in the axial skeleton of patients with axSpA. This viewpoint discusses the relevance of structural changes in the SIJ in comparison to the spine and in relation to functional outcomes and mobility.
Plasma thymic stromal lymphopoietin (TSLP) in adults with non-severe asthma: the EGEA study
Authors: Ibrahim Bakari , Achour Djamal , Zerimech Farid , de Nadai Patricia , Siroux Valerie , Tsicopoulos Anne , Matran Régis , Granger Vanessa , Nadif Rachel
Published: December 2022

Thymic stromal lymphopoietin (TSLP), a cytokine involved in severe asthma treatment, was never studied in non-severe asthma.

Among 969 adults from a large epidemiological study, cross-sectional analyses showed that plasma TSLP levels were associated with increased age and BMI, male sex, smoking and high TSLP levels (one IQR increase) with current asthma and poor lung function. High TSLP levels were also associated with persistence of asthma attacks (aOR=2.14 (95% CI 1.23 to 3.72)) and dyspnoea (aOR=2.71 (95% CI 1.39 to 5.28)) 10 years later.

Our results suggest that TSLP could be a cytokine of interest in non-severe asthma, and its determinants of circulating levels could be considered in asthma management.