bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of dolutegravir/rilpivirine in real‐world clinical practice. GeSIDA study 1119
Authors: Palacios R. , Gómez‐Ayerbe C. , Casado J. L. , Tejerina F. , Montes M. L. , Castaño M. , Ocampo A. , Rial D. , Ribera E. , Galindo M. J. , Hidalgo C. , Fariñas C. , Montero M. , Payeras T. , Fanjul F. , de la Torre J. , Santos J.
Published: April 2023

Introduction

Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real‐world clinical practice.

Methods

Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed.

Results

A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/μL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non‐nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV‐RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1–92.6) by intention‐to‐treat (ITT) and 94.2% (95% CI 91.3–96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low‐density lipoprotein‐cholesterol, glutamic–pyruvic transaminase (GPT), gamma‐glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate.

Conclusions

This study confirms the effectiveness, tolerability and safety of DTG/RPV in real‐world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one‐third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.
Gut mycobiome dysbiosis and its impact on intestinal permeability in attention‐deficit/hyperactivity disorder
Authors: Wang Liang‐Jen , Li Sung‐Chou , Yeh Yuan‐Ming , Lee Sheng‐Yu , Kuo Ho‐Chang , Yang Chia‐Yu
Published: April 2023

Background

Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention‐deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD.

Methods

Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples and the internal transcribed spacer regions were sequenced using high‐throughput next‐generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco‐2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function.

Results

The β‐diversity (the species diversity between two communities), but not α‐diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and a significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco‐2 cells.

Conclusions

The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.
Behavioral change stage might moderate the impact of multifaceted interventions on non‐attendance from medical care among patients with type 2 diabetes: The Japan Diabetes Outcome Intervention Trial‐2 Large‐Scale Trial 007 (J‐DOIT2‐LT007)
Authors: Bouchi Ryotaro , Noda Mitsuhiko , Hayashino Yasuaki , Goto Atsushi , Yamazaki Katsuya , Suzuki Hikari , Furukawa Toshiaki A , Izumi Kazuo , Kobayashi Masashi ,   J‐DOIT2 Study Group
Published: April 2023

Aims/Introduction

Non‐attendance from regular medical care is a major problem in diabetes patients. This study aimed to examine the impact of a multifaceted lifestyle intervention by face‐to‐face approach (FFA) on non‐attendance from regular medical care in comparison with that by telephone from the technical support center (TSC).

Materials and Methods

This was secondary analysis from a 1‐year, prospective, cluster randomized, intervention study. Patients with type 2 diabetes, who were regularly visiting primary care physicians cluster‐randomized into the control or intervention (TSC or FFA according to resource availability of the district medical associations) groups, were consecutively recruited. The primary end‐point was non‐attendance from regular medical care. The interaction between the type of intervention (TSC vs FFA) and behavioral change stage (pre‐ vs post‐action stage) in diet and exercise for the dropout rate was assessed.

Results

Among the 1,915 participants (mean age 56 ± 6 years; 36% women) enrolled, 828, 564 and 264 patients belonged to the control, TSC and FFA groups, respectively. We found evidence suggestive of an interaction between the intervention type and behavioral change stage in diet (P = 0.042) and exercise (P = 0.038) after adjusting for covariates. The hazard ratios (95% confidence interval) of FFA to TSC were 0.21 (0.05–0.93) and 7.69 (0.50–117.78) in the pre‐action and post‐action stages for diet, respectively, whereas they were 0.20 (0.05–0.92) and 4.75 (0.29–73.70) in the pre‐action and post‐action stages for exercise.

Conclusions

Among diabetes patients, the impact of multifaceted intervention on non‐attendance from medical care might differ by the behavioral change stage.
13‐year population survey of the critically endangered European eel in the southern Mediterranean region (Algeria)
Authors: Tahri Mardja , Panfili Jacques
Published: April 2023

A 13‐year biomonitoring survey was carried out on the European eel, Anguilla anguilla for the first time in North Africa (Algeria) where there is a serious lack of information on the species. The study targeted specimens populating the only four sites where the species is both potentially present and legally exploited (Lake Oubeira, Lake Tonga, Mellah lagoon and Mafragh estuary). A total of 1370 individuals were sampled ranging from 17 to 113 cm in length, 19 to 2642 g in weight and 0.7 months to 6.6 years old, age being estimated from otolith growth marks. Otolith interpretation and age estimation were generally unambiguous at all four sites. According to the EELREP silvering index, the highest proportion of silver females was captured in fresh water (46% in Lake Oubeira and 25% in Lake Tonga), whereas a third were present in brackish water (Mafragh and Mellah). The sex ratio was in favour of females, and silver males were found to mature early (mean length 40 ± 1 cm, mean weight 123 ± 28 g and mean age 2 ± 0.6 years). Growth differed at the four sites, and the growth rate was highest in Lake Oubeira and asymptotic length highest in Mellah lagoon. Metamorphosis from the yellow resident stage to the silver migrating stage occurred very early in the eels' continental life (between 3 and 4 years of age). Results highlight rapid growth in these Algerian sites, and earlier silvering than in eels living in European waters, suggesting different life‐history traits of A. anguilla in North African waters, influenced by environmental conditions.
Error analysis of Raven's Coloured Progressive Matrices in children and adolescents with cerebral palsy
Authors: Asano D. , Takeda M. , Nobusako S. , Morioka S.
Published: April 2023

Background

Analysis of the errors in the Raven's Coloured Progressive Matrices (RCPM) has been previously performed for children with intellectual disabilities but has not been investigated for those with cerebral palsy (CP). This study aimed to investigate whether the types and positions of errors made by individuals with CP differed from those made by typically developing (TD) controls.

Methods

Forty‐five participants with CP aged 4–18 years and 30 TD children aged 3–9 years underwent RCPM testing. We first compared the RCPM performance and error characteristics between the groups and then examined the association between RCPM and the severity of CP and receptive vocabulary in the CP group.

Results

The results showed that while mean total scores in the two groups were comparable, the types and positions of errors made by individuals with CP differed from those of TD controls. The development of non‐verbal intelligence in children with CP increased with age; when controlling for age, non‐verbal intelligence was significantly correlated with all three functional levels of CP severity and receptive vocabulary.

Conclusions

This study provides valuable insights into the problem‐solving strategies employed by children with CP.
Effect of laboratory and sample storage factors on urinary protein:creatinine ratios and clinical decision making in cats
Authors: Mortier Femke , Daminet Sylvie , Duchateau Luc , Demeyere Kristel , Meyer Evelyne , Paepe Dominique
Published: April 2023

Background

Urinary protein:creatinine ratio (UPC) results affect the diagnosis, prognosis, and therapy of chronic kidney disease in cats.

Objectives

To investigate the interlaboratory and intralaboratory variability and the effect of storage on UPC and International Renal Interest Society (IRIS) proteinuria substaging in cats.

Animals

Healthy and diseased client‐owned cats.

Methods

Prospective study. Urine of 60 cats was randomly sent to 4 (of 9) participating laboratories (to assess interlaboratory variability) and per cat, 2 laboratories each received 2 aliquots (to determine intralaboratory variability). Samples of 23 cats were analyzed in the same laboratory the day of collection, after preservation at 22°C for 1 day and at 4°C during 1‐7 days (short‐term storage) and at −24°C and −80°C for 6‐12 months (long‐term storage). Storage conditions were compared by equivalence testing.

Results

UPCs showed good interclass correlation (ICC‐inter, 0.90) and excellent intraclass correlation (ICC‐intra, 0.99). However, in 30/60 (50%) cats at least 1 of 4 laboratories assigned a different IRIS proteinuria substage. Urinary protein:creatinine ratio remained stable with short‐term storage, but not after 6 months storage at −24°C and after 12 months storage at −24°C or −80°C. Long‐term storage caused a change in IRIS proteinuria substage in 27% of cats, whereas a shift occurred only in 4% of cats during short‐term storage.

Conclusions and Clinical Importance

Laboratory choice for UPC measurement can result in different IRIS substaging for the same cat, whereas urine storage at room temperature for 1 day or in the refrigerator for up to 7 days does not clinically affect UPC.
Bicameralism Hinges on Legislative Professionalism
Authors: Brown Adam R. , Garlick Alex
Published: April 2023

Bicameralism is a nearly universal feature of American legislatures, yet its functional impact on legislative outcomes is uncertain. Proponents have claimed that bicameralism would produce better outcomes than unicameralism, as adding a deliberative element prevents the passage of faulty legislation. For bicameralism to work in this fashion, we argue lawmakers must have enough time and resources to meaningfully evaluate legislation produced by the other chamber. We find such behavior is most likely to take place in professionalized state legislatures, evidenced by a lower concurrence rate in the second chamber for bills passed by the first chamber. In state legislatures with less policy capacity, by contrast, the chambers act in a more parallel fashion, dividing the agenda and largely endorsing the other chamber's legislation.
Surface and diving metabolic rates, and dynamic aerobic dive limits (dADL) in near‐ and off‐shore bottlenose dolphins, Tursiops spp., indicate that deep diving is energetically cheap
Authors: Fahlman Andreas , Allen Austin S. , Blawas Ashley , Sweeney Jay , Stone Rae , Trainor Robyn Faulkner , Jensen Frants H. , McHugh Katherine , Allen Jason B. , Barleycorn Aaron A. , Wells Randall S.
Published: April 2023

High‐resolution dive depth and acceleration recordings from nearshore (Sarasota Bay, dive depth < 30 m), and offshore (Bermuda) bottlenose dolphins (Tursiops spp.) were used to estimate the diving metabolic rate (DMR) and the locomotor metabolic rate (LMR, L O2/min) during three phases of diving (descent, bottom, and ascent). For shallow dives (depth ≤ 30 m), we found no differences between the two ecotypes in the LMR during diving, nor during the postdive shallow interval between dives. For intermediate (30 m < depth ≤ 100 m) and deep dives (depth > 100 m), the LMR was significantly higher during ascent than during descent and the bottom phase by 59% and 9%, respectively. In addition, the rate of change in depth during descent and ascent (meters/second) increased with maximal dive depth. The dynamic aerobic dive limit (dADL) was calculated from the estimated DMR and the estimated predive O2 stores. For the Bermuda dolphins, the dADL decreased with dive depth, and was 18.7, 15.4, and 11.1 min for shallow, intermediate, and deep dives, respectively. These results provide a useful approach to understand the complex nature of physiological interactions between aerobic metabolism, energy use, and diving capacity.
The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study
Authors: Jaafari Hussain , Houghton Lesley A. , West Robert M. , Agrawal Anurag , Aziz Imran , Black Christopher J. , Corsetti Maura , Shuweihdi Farag , Eugenicos Maria , Paine Peter A. , Ford Alexander C. , Whorwell Peter J. , Bangdiwala Shrikant I. , Palsson Olafur S. , Sperber Ami D. , Vasant Dipesh H.
Published: April 2023

Background

There are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online.

Methods

Participants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in‐depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together.

Key Results

The proportion of participants with at least one DGBI was lower in UK participants compared with in the other 25 countries (37.6% 95% CI 35.5%–39.7% vs. 41.2%; 95% CI 40.8%–41.6%,p = 0.001). The UK prevalence of 14 of 22 Rome IV DGBI, including irritable bowel syndrome (4.3%) and functional dyspepsia (6.8%), was similar to the other countries. Fecal incontinence, opioid‐induced constipation, chronic nausea and vomiting, and cannabinoid hyperemesis (p < 0.05) were more prevalent in the UK. Cyclic vomiting, functional constipation, unspecified functional bowel disorder, and proctalgia fugax (p < 0.05) were more prevalent in the other 25 countries. Diet in the UK population consisted of higher consumption of meat and milk (p < 0.001), and lower consumption of rice, fruit, eggs, tofu, pasta, vegetables/legumes, and fish (p < 0.001).

Conclusions and Inferences

The prevalence and burden of DGBI is consistently high in the UK and in the rest of the world. Opioid prescribing, cultural, dietary, and lifestyle factors may contribute to differences in the prevalence of some DGBI between the UK and other countries.
Face‐to‐face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population‐based research
Authors: Sperber Ami D. , Bor Serhat , Fang Xuicai , Bangdiwala Shrikant I. , Drossman Douglas A. , Ghoshal Uday C. , Simren Magnus , Tack Jan , Whitehead William E. , Dumitrascu Dan L. , Fukudo Shin , Kellow John , Okeke Edith , Quigley Eamonn M. M. , Schmulson Max , Whorwell Peter , Archampong Timothy , Adibi Payman , Andresen Viola , Benninga Marc A. , Bonaz Bruno , Fernandez Luis Bustos , Choi Suck Chei , Corazziari Enrico S. , Francisconi Carlos , Hani Albis , Lazebnik Leonid , Lee Yeong Yeh , Mulak Agata , Rahman M. Masudur , Santos Javier , Setshedi Mashiko , Syam Ari Fahrial , Vanner Stephen , Wong Reuben K. , Lopez‐Colombo Aurelio , Costa Valeria , Dickman Ram , Kanazawa Motoyori , Keshteli Ammar Hassanzadeh , Khatun Rutaba , Maleki Iradj , Poitras Pierre , Pratap Nitesh , Stefanyuk Oksana , Thomson Sandie , Buyruk Murat , Unal Nalan , Huang Dan , Song Jun , Hreinsson Johann P. , Palsson Olafur S.
Published: April 2023

Background and Aims

The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut–Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In‐person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences.

Methods

The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences.

Results

Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology‐related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity.

Conclusions

The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.
Toward understanding links between the microbiome and neurotransmitters
Authors: Lynch Jonathan B. , Hsiao Elaine Y.
Published: April 2023

The gut microbiota modulates neurobiological activity in various animal lineages. This is often proposed to occur through interactions with neurotransmitters and other neuromodulatory molecules in the host. Our commentary will discuss recent research that establishes microbiota–neurotransmitter connections, gaps in current understanding, and outstanding questions that may guide future advances in the field of microbiota–nervous system interactions.
Gallstone ileus at 17 years after living donor liver transplantation: A case report
Authors: Komine Ryuji , Sakamoto Seisuke , Uchida Hajime , Nakao Toshimasa , Kodama Tasuku , Okada Noriki , Shimizu Seiichi , Fukuda Akinari , Kasahara Mureo
Published: April 2023

Background

Gallstone ileus (GI) occurs in <0.1% of all cases of mechanical bowel obstruction. There have been a few reports of GI occurring after Kasai procedures or Roux‐en‐Y anastomosis for bariatric surgery. We herein report a case of GI that occurred over 17 years after liver transplantation (LT).

Case Report

A 33‐year‐old woman who had undergone living donor LT for biliary atresia at 16 years old and had been regularly followed on an outpatient basis in our hospital presented with the sudden onset of increased abdominal distension, pain, and nausea. Enhanced abdominal computed tomography showed dilatation of the intrahepatic bile duct and the whole intestinal tract of the Roux limb as well as ischemic changes near the jejuno‐jejunal anastomosis. On laparotomy, a movable and hard foreign body was palpated in the intestinal tract close to the jejuno‐jejunal anastomosis site. Enterotomy was performed, and a 4‐cm gallstone was removed. The patient had a good postoperative course and was discharged on postoperative day 12.

Conclusions

Although GI after LT is a rare complication, it may need to be differentiated as a cause of ileus. An accurate differential diagnosis and early reliable intervention for stone removal will help prevent serious bowel complication, which may lead to graft dysfunction.
Anisotropic cell growth and cell wall structure in lenticular cell of Valonia utricularis (Ulvophyceae)
Authors: Mine Ichiro , Inoue Yusuke , Yamamoto Takuji , Sekida Satoko
Published: April 2023

During cell division of the giant‐celled green alga, Valonia utricularis, a lenticular cell is newly formed, which grows from disc‐shaped to globular to obovoid. During the early developmental stages of growth, the cell surface shows a remarkable outward protrusion. In the present study, the anisotropy of cell growth, i.e. the difference between cell surface extension in meridional and radial orientation, was investigated by analyzing the movement of the surface markers in a living cell. Growth was isotropic around the cell zenith but of two different kinds of anisotropic growth in other regions; radial extension was dominant in cell periphery and meridional extension in intermediate regions between zenith and periphery. Moreover, local orientation of cellulose microfibrils was observed on the inner surface of the cell wall during different stages of early development in lenticular cell using an atomic force microscope. Cellulose microfibrils showed meridional orientation overall and this phenomenon was most remarkable in the periphery of the cell, suggesting the possibility of cellulose microfibrils promoting radial extension of cells by suppressing meridional extension of cell wall.
A systematic exploration of attentional load effects on the C1 ERP component
Authors: Qin Nan , Crespi Francesca , Proverbio Alice Mado , Pourtois Gilles
Published: April 2023

The C1 ERP component reflects the earliest visual processing in V1. However, it remains debated whether attentional load can influence it or not. We conducted two EEG experiments to investigate the effect of attentional load on the C1. Task difficulty was manipulated at fixation using an oddball detection task that was either easy (low load) or difficult (high load), while the distractor was presented in the upper visual field (UVF) to score the C1. In Experiment 1, we used a block design and the stimulus onset asynchrony (SOA) between the central stimulus and the peripheral distractor was either short or long. In Experiment 2, task difficulty was manipulated on a trial‐by‐trial basis using a visual cue, and the peripheral distractor was presented either before or after the central stimulus. The results showed that the C1 was larger in the high compared to the low load condition irrespective of SOA in Experiment 1. In Experiment 2, no significant load modulation of the C1 was observed. However, we found that the contingent negative variation (CNV) was larger in the low compared to the high load condition. Moreover, the C1 was larger when the peripheral distractor was presented after than before the central stimulus. Combined together, these results suggest that different top‐down control processes can influence the initial feedforward stage of visual processing in V1 captured by the C1 ERP component.
The management of the sea lice in Chile: A review
Authors: Bravo Sandra , Treasurer James
Published: April 2023

Sea lice infestations have the largest economic and biological impact on salmon farming in Chile, similar to that seen in salmon‐producing countries in the northern hemisphere. Caligus teres infesting coho salmon (Oncorhynchus kisutch) was first recorded in 1981, but Caligus rogercresseyi has been the predominant species infesting Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) from 1997. In contrast, coho salmon has been shown to be resistant to this sea louse species. Regulations to establish integrated pest management of sea lice were implemented by the Chilean authority in 2007. However, to date, pharmacological medicines have been the main tool used by the salmon farming industry in Chile to manage sea lice, although non‐pharmacological treatments have been available since 2016. Production of farmed salmon reached 978.274 tons in 2021 and 7.72 g of medicines was prescribed per ton of harvested salmon. The highest volumes used in that year were Azamethiphos (47%) and hexaflumuron (45.5%), in addition to 5532 tons of hydrogen peroxide. This review updates the current management of sea lice in Chile and also summarizes the biological knowledge of this important parasite.
Seeding density of wildflower mixes affects nectar production in a focal plant species
Authors: Neece Jillian , Brokaw Julia , Coker Adara , Bruninga‐Socolar Bethanne
Published: April 2023

Restoring habitat with diverse flowering plants is an important tool for pollinator conservation. Pollinator‐friendly seed mixes used in restorations vary in seeding density and forb‐to‐grass seed ratio, but few studies have examined the potential differences in nectar quantity and quality produced among mixes. We quantified the nectar rewards of Penstemon digitalis in plots planted with seed mixes of varying seeding density and forb‐to‐grass ratios by measuring nectar volume and sugar concentration. We found that nectar sugar concentration of P. digitalis was greatest at low seeding density, suggesting pollinator support in low‐cost seed mixes. Understanding how seed mix design parameters impact pollinator food resources is a key next step in habitat restoration for pollinator conservation.
Gait speed in idiopathic pulmonary fibrosis: Quickly stepping in the right direction
Authors: Khor Yet H. , Ryerson Christopher J.
Published: April 2023

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Exporting and sourcing strategies
Authors: Kang Youngho , Whang Unjung
Published: April 2023

This study uses firm‐level panel data for South Korea for the period 2006–2015, to investigate changes in firms' sourcing behaviors after these firms start exporting. The data studied includes detailed information on firms' export status, whether their purchases of intermediate inputs were domestic or from foreign markets, and whether the supplier firms were affiliated or non‐affiliated. To estimate the effects of exporting on firms' sourcing strategies, we employ a difference‐in‐differences estimator with propensity score matching. The main finding is that participation in export markets leads to the increased use of intermediate inputs purchased from foreign suppliers; it also increases these firms' sourcing from affiliated parties relative to sourcing from non‐affiliated suppliers. These changes in firms' sourcing compositions after their entry into export markets are mainly driven by purchasing rather than subcontracting. These findings point out that firms that newly participate in exporting tend to improve their product competitiveness by increasing the proportion of their intermediate inputs from foreign affiliates. It is also possible that these firms expanded their foreign networks after they begin export activities, and this plays a role in how and where they source their intermediate inputs.
An anchored joint acceptance account of group justification
Authors: Schwengerer Lukas
Published: April 2023

When does a group justifiedly believe that p? One answer to this question has been developed first by Schmitt and then by Hakli: when the group members jointly accept a reason for the belief. Call this the joint acceptance account of group justification. Their answer has great explanatory power, providing us with a way to account for cases in which the group's justification can diverge from the justification individual members have. Unfortunately, Jennifer Lackey developed a powerful argument against joint acceptance accounts. She argues that these accounts lead to epistemically arbitrary reasons and therefore justification at will. Group justification loses the necessary connection to the world to be truth‐conducive. In this paper I develop a new form of a joint acceptance account that can deal with Lackey's examples: the anchored joint acceptance account of group justification. I argue that properly understanding the role of epistemic expectations can help us form the best version of a joint acceptance account. While justification is only generated by joint acceptance of evidence, the evidential expectations towards a group are anchored in the group members. This anchoring guarantees that groups cannot manipulate their ultima facie justification illegitimately.
Evaluation of focal adhesion mediated subcellular curvature sensing in response to engineered extracellular matrix
Authors: Bowers Daniel T. , McCulloch Mary Elizabeth , Brown Justin L.
Published: April 2023

Fibril curvature is bioinstructive to attached cells. Similar to natural healthy tissues, an engineered extracellular matrix can be designed to stimulate cells to adopt desired phenotypes. To take full advantage of the curvature control in biomaterial fabrication methodologies, an understanding of the response to fibril subcellular curvature is required. In this work, we examined morphology, signaling, and function of human cells attached to electrospun nanofibers. We controlled curvature across an order of magnitude using nondegradable poly(methyl methacrylate) (PMMA) attached to a stiff substrate with flat PMMA as a control. Focal adhesion length and the distance of maximum intensity from the geographic center of the vinculin positive focal adhesion both peaked at a fiber curvature of 2.5 μm-1 (both ∼2× the flat surface control). Vinculin experienced slightly less tension when attached to nanofiber substrates. Vinculin expression was also more affected by a subcellular curvature than structural proteins α-tubulin or α-actinin. Among the phosphorylation sites we examined (FAK397, 576/577, 925, and Src416), FAK925 exhibited the most dependance on the nanofiber curvature. A RhoA/ROCK dependance of migration velocity across curvatures combined with an observation of cell membrane wrapping around nanofibers suggested a hybrid of migration modes for cells attached to fibers as has been observed in 3D matrices. Careful selection of nanofiber curvature for regenerative engineering scaffolds and substrates used to study cell biology is required to maximize the potential of these techniques for scientific exploration and ultimately improvement of human health.
ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer
Authors: Li Dan , Zhan Yu , Wang Naitao , Tang Fanying , Lee Cindy J. , Bayshtok Gabriella , Moore Amanda R. , Wong Elissa W. P. , Pachai Mohini R. , Xie Yuanyuan , Sher Jessica , Zhao Jimmy L. , Khudoynazarova Makhzuna , Gopalan Anuradha , Chan Joseph , Khurana Ekta , Shepherd Peter , Navone Nora M. , Chi Ping , Chen Yu
Published: April 2023

The mechanisms underlying
ETS
-driven prostate cancer initiation and progression remain poorly understood due to a lack of model systems that recapitulate this phenotype. We generated a genetically engineered mouse with prostate-specific expression of the
ETS
factor, ETV4, at lower and higher protein dosage through mutation of its degron. Lower-level expression of ETV4 caused mild luminal cell expansion without histologic abnormalities, and higher-level expression of stabilized ETV4 caused prostatic intraepithelial neoplasia (mPIN) with 100% penetrance within 1 week. Tumor progression was limited by p53-mediated senescence and
Trp53
deletion cooperated with stabilized ETV4. The neoplastic cells expressed differentiation markers such as Nkx3.1 recapitulating luminal gene expression features of untreated human prostate cancer. Single-cell and bulk RNA sequencing showed that stabilized ETV4 induced a previously unidentified luminal-derived expression cluster with signatures of cell cycle, senescence, and epithelial-to-mesenchymal transition. These data suggest that
ETS
overexpression alone, at sufficient dosage, can initiate prostate neoplasia.
Globally distributed subducted materials along the Earth’s core-mantle boundary: Implications for ultralow velocity zones
Authors: Hansen Samantha E. , Garnero Edward J. , Li Mingming , Shim Sang-Heon , Rost Sebastian
Published: April 2023

Ultralow velocity zones (ULVZs) are the most anomalous structures within the Earth’s interior; however, given the wide range of associated characteristics (thickness and composition) reported by previous studies, the origins of ULVZs have been debated for decades. Using a recently developed seismic analysis approach, we find widespread, variable ULVZs along the core-mantle boundary (CMB) beneath a largely unsampled portion of the Southern Hemisphere. Our study region is not beneath current or recent subduction zones, but our mantle convection simulations demonstrate how heterogeneous accumulations of previously subducted materials could form on the CMB and explain our seismic observations. We further show that subducted materials can be globally distributed throughout the lowermost mantle with variable concentrations. These subducted materials, advected along the CMB, can provide an explanation for the distribution and range of reported ULVZ properties.
Revealing the key role of molecular packing on interface spin polarization at two-dimensional limit in spintronic devices
Authors: Luo Zhongzhong , Song Xiangxiang , Liu Xiaolong , Lu Xiangqian , Yao Yu , Zeng Junpeng , Li Yating , He Daowei , Zhao Huijuan , Gao Li , Yu Zhihao , Niu Wei , Sun Huabin , Xu Yong , Liu Shujuan , Qin Wei , Zhao Qiang
Published: April 2023

Understanding spinterfaces between magnetic metals and organic semiconductors is essential to unlock the great potentials that organic materials host for spintronic applications. Although plenty of efforts have been devoted to studying organic spintronic devices, exploring the role of metal/molecule spinterfaces at two-dimensional limit remains challenging because of excessive disorders and traps at the interfaces. Here, we demonstrate atomically smooth metal/molecule interfaces through nondestructively transferring magnetic electrodes on epitaxial grown single-crystalline layered organic films. Using such high-quality interfaces, we investigate spin injection of spin-valve devices based on organic films of different layers, in which molecules are packed in different manners. We find that the measured magnetoresistance and the estimated spin polarization increase markedly for bilayer devices compared with their monolayer counterparts. These observations reveal the key role of molecular packing on spin polarization, which is supported by density functional theory calculations. Our findings provide promising routes toward designing spinterfaces for organic spintronic devices.
Identification of 113 new histone marks by CHiMA, a tailored database search strategy
Authors: Gao Jinjun , Sheng Xinlei , Du Jianfeng , Zhang Di , Han Chang , Chen Yue , Wang Chu , Zhao Yingming
Published: April 2023

Shotgun proteomics has been widely used to identify histone marks. Conventional database search methods rely on the “target-decoy” strategy to calculate the false discovery rate (FDR) and distinguish true peptide-spectrum matches (PSMs) from false ones. This strategy has a caveat of inaccurate FDR caused by the small data size of histone marks. To address this challenge, we developed a tailored database search strategy, named “Comprehensive Histone Mark Analysis (CHiMA).” Instead of target-decoy–based FDR, this method uses “50% matched fragment ions” as the key criterion to identify high-confidence PSMs. CHiMA identified twice as many histone modification sites as the conventional method in benchmark datasets. Reanalysis of our previous proteomics data using CHiMA led to the identification of 113 new histone marks for four types of lysine acylations, almost doubling the number of previously reported marks. This tool not only offers a valuable approach for identifying histone modifications but also greatly expands the repertoire of histone marks.
Surface engineering toward stable lithium metal anodes
Authors: Lu Gongxun , Nai Jianwei , Luan Deyan , Tao Xinyong , Lou Xiong Wen (David)
Published: April 2023

The lithium (Li) metal anode (LMA) is susceptible to failure due to the growth of Li dendrites caused by an unsatisfied solid electrolyte interface (SEI). With this regard, the design of artificial SEIs with improved physicochemical and mechanical properties has been demonstrated to be important to stabilize the LMAs. This review comprehensively summarizes current efficient strategies and key progresses in surface engineering for constructing protective layers to serve as the artificial SEIs, including pretreating the LMAs with the reagents situated in different primary states of matter (solid, liquid, and gas) or using some peculiar pathways (plasma, for example). The fundamental characterization tools for studying the protective layers on the LMAs are also briefly introduced. Last, strategic guidance for the deliberate design of surface engineering is provided, and the current challenges, opportunities, and possible future directions of these strategies for the development of LMAs in practical applications are discussed.
Does the visual word form area split in bilingual readers? A millimeter-scale 7-T fMRI study
Authors: Zhan Minye , Pallier Christophe , Agrawal Aakash , Dehaene Stanislas , Cohen Laurent
Published: April 2023

In expert readers, a brain region known as the visual word form area (VWFA) is highly sensitive to written words, exhibiting a posterior-to-anterior gradient of increasing sensitivity to orthographic stimuli whose statistics match those of real words. Using high-resolution 7-tesla functional magnetic resonance imaging (fMRI), we ask whether, in bilingual readers, distinct cortical patches specialize for different languages. In 21 English-French bilinguals, unsmoothed 1.2-millimeters fMRI revealed that the VWFA is actually composed of several small cortical patches highly selective for reading, with a posterior-to-anterior word-similarity gradient, but with near-complete overlap between the two languages. In 10 English-Chinese bilinguals, however, while most word-specific patches exhibited similar reading specificity and word-similarity gradients for reading in Chinese and English, additional patches responded specifically to Chinese writing and, unexpectedly, to faces. Our results show that the acquisition of multiple writing systems can indeed tune the visual cortex differently in bilinguals, sometimes leading to the emergence of cortical patches specialized for a single language.
The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
Authors: Liu Huadie , Zhai Lukai , Liu Ye , Lu Di , Vander Ark Alexandra , Yang Tao , Krawczyk Connie M.
Published: April 2023

Women experience osteoporosis at higher rates than men. Aside from hormones, the mechanisms driving sex-dependent bone mass regulation are not well understood. Here, we demonstrate that the X-linked H3K4me2/3 demethylase KDM5C regulates sex-specific bone mass. Loss of KDM5C in hematopoietic stem cells or bone marrow monocytes increases bone mass in female but not male mice. Mechanistically, loss of KDM5C impairs the bioenergetic metabolism, resulting in impaired osteoclastogenesis. Treatment with the KDM5 inhibitor reduces osteoclastogenesis and energy metabolism of both female mice and human monocytes. Our report details a sex-dependent mechanism for bone homeostasis, connecting epigenetic regulation to osteoclast metabolism and positions KDM5C as a potential target for future treatment of osteoporosis in women.
Contributions of Ccr4 and Gcn2 to the Translational Response of
C. neoformans
to Host-Relevant Stressors and Integrated Stress Response Induction
Authors: Knowles Corey M. , Goich David , Bloom Amanda L. M. , Kalem Murat C. , Panepinto John C.
Published: April 2023

Cryptococcus neoformans
is a human pathogen capable of causing devastating infections. It must rapidly adapt to changing environments as it leaves its niche in the soil and enters the human lung.
Spontaneously Produced Lysogenic Phages Are an Important Component of the Soybean
Bradyrhizobium
Mobilome
Authors: Joglekar Prasanna , Ferrell Barbra D. , Jarvis Tessa , Haramoto Kona , Place Nicole , Dums Jacob T. , Polson Shawn W. , Wommack K. Eric , Fuhrmann Jeffry J.
Published: April 2023

Previous studies have shown that IS and plasmids mediate HGT of symbiotic nodulation (
nod
) genes in soybean bradyrhizobia; however, these events require close cell-to-cell contact, which could be limited in soil environments. Bacteriophage-assisted gene transduction through spontaneously produced prophages provides a stable means of HGT not limited by the constraints of proximal cell-to-cell contact.
Chromobacterium
Biopesticide Exposure Does Not Select for Resistance in
Aedes
Mosquitoes
Authors: Engdahl Cecilia Springer , Caragata Eric P. , Tavadia Mihra , Dimopoulos George
Published: April 2023

Vector control is an essential part of mitigating diseases caused by pathogens that mosquitoes spread. Modern vector control is highly reliant on using synthetic insecticides to eliminate mosquito populations before they can cause disease.
Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans
Authors: Bowring Bethany Grace , Sethiya Pooja , Desmarini Desmarini , Lev Sophie , Tran Le Lisa , Bahn Yong-Sun , Lee Seung-Heon , Toh-e Akio , Proschogo Nicholas , Savage Tom , Djordjevic Julianne Teresa
Published: April 2023

Invasive fungal diseases cause more than 1.5 million deaths per year, with an estimated 181,000 of these deaths attributable to Cryptococcal meningitis. Despite the high mortality, treatment options are limited.
Tectono-magmatic response to the geometric evolution of slab breakoff in the Paleo-Tethys Ocean: Constraints from Late Triassic granites in the Qiangtang block, northern Tibet
Authors: Wu Hao , Liu Xi-Jun , Chen Jing-Wen , Li Cai , Yang Rui , Jiang Zi-Qi
Published: April 2023

Slab breakoff can explain the postcollisional igneous and metamorphic events in many collisional orogens and triggers the transition from initial continental collision to deep subduction. However, the relationship between the deep-seated geometry of slab breakoff and shallow tectono-magmatic events remains unclear. In this study, we report new geochronological, geochemical, and Hf isotope data for granitic rocks from the Qiangtang block. Three granitic samples yielded zircon U-Pb ages of 226−214 Ma and mostly gave negative zircon εHf(t) values of −20.1 to +0.57. These granitoids are K-rich, calc-alkaline, magnesian, and metaluminous to weakly peraluminous. We propose that the granites were generated by partial melting of compositionally heterogeneous lower crust in the Southern Qiangtang block. Our new data, along with previously published data for igneous and metamorphic rocks in the Qiangtang block, suggest that the Longmu Co−Shuanghu suture zone represents a remnant of the closure of the Paleo-Tethys Ocean, and that the Late Triassic tectono-magmatic evolution was controlled by slab breakoff after continental collision. The contrasting magmatic and metamorphic ages show that the two stages of tectono-magmatic activity in the Late Triassic were due to a change in the subduction angle of the continental lithosphere from steep (225−215 Ma) to shallow (215−205 Ma) during slab breakoff. Furthermore, we infer that slab breakoff of the oceanic lithosphere caused extensive crustal melting and reworking and initiated far-field subduction. Our results provide new insights into the slab breakoff processes that control the geometry of subducting continental lithosphere and related postcollisional magmatic and metamorphic events in collision zones.
Invasive bacterial infection in children with fever and petechial rash in the emergency department: a national prospective observational study
Authors: Storch-De-Gracia Pilar , Fernández Jose Luis , Velasco Roberto , Saez Itsaso , Rodrigo Rocío , Yañez Sandra , Castellarnau Ester , Gil Elena , del Rio Patricia , Garrido Estíbaliz , Castaño Antón , Perez Álvaro , Cabrerizo María , Hernández María , Pérez Juan Jesús , de la Torre María José , Nadal Gemma , Martínez Javier , Sánchez-Tatay Victoria
Published: April 2023

Objective

To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae.

Design

A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019.

Patients

A total of 688 patients were recruited.

Main outcome measures

The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI.

Results

Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3–51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%).

Conclusions

The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI.