bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact on glucometric variables and quality of life of the advanced hybrid closed‐loop system in pediatric and adolescent type 1 diabetes
Authors: Lendínez‐Jurado Alfonso , Gómez‐Perea Ana , Ariza‐Jiménez Ana B. , Tapia‐Ceballos Leopoldo , Becerra‐Paz Icía , Martos‐Lirio María F. , Moreno‐Jabato Fernando , Leiva‐Gea Isabel
Published: June 2023

Background

In recent years, technological advances in the field of diabetes have revolutionized the management, prognosis, and quality of life of diabetes patients and their environment. The aim of our study was to evaluate the impact of implementing the MiniMed 780G closed‐loop system in a pediatric and adolescent population previously treated with a continuous subcutaneous insulin infusion pump and intermittent glucose monitoring.

Methods

Data were collected from 28 patients with type 1 diabetes aged 6 to 17 years, with a follow‐up of 6 months. We included both glucometric and quality of life variables, as well as quality of life in primary caregivers. Metabolic control variables were assessed at baseline (before system change) and at different cutoff points after initiation of the closed‐loop system (48 hours, 7 days, 14 days, 21 days, 1 month, 3 months, 6 months).

Results

Time in range 70–180 mg/dL increased from 59.44% at baseline to 74.29% in the first 48 hours after automation of the new system, and this improvement was maintained at the other cutoff points, as was time in hyperglycemia 180–250 mg/dL (24.44% at baseline to 18.96% at 48 hours) and >250 mg/dL (11.71% at baseline to 3.82% at 48 hours).

Conclusions

Our study showed an improvement in time in range and in all time spent in hyperglycemia from the first 48 hours after the automation of the system, which was maintained at 6 months.
High‐resolution peripheral quantitative computed tomography for the evaluation of bone erosions of metatarsophalangeal joints in patients with rheumatoid arthritis
Authors: Meinhardsson Jørgen Martin , Klose‐Jensen Rasmus , Therkildsen Josephine , Langdahl Bente , Hauge Ellen‐Margrethe , Keller Kresten Krarup
Published: June 2023

Objectives

To compare if the 4th and 5th metatarsophalangeal (MTP) joints evaluated by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) could classify more patients with erosive rheumatoid arthritis (RA) compared with conventional radiography (CR) of the hands, wrists, and feet. Furthermore, we characterize and quantify bone erosions in the two MTP joints by HR‐pQCT.

Methods

This single‐center cross‐sectional study included patients with established RA (disease duration ≥5 years). Blinded to patient data, the number and volume of erosions in the 4th and 5th MTP joints were measured by HR‐pQCT, whereas the erosive scores by CR of 44 joints in the hands, wrists, and feet were assessed according to the Sharp/van der Heijde method.

Results

Among 42 participants, 30 patients were classified with erosive RA and 12 with non‐erosive RA by CR. HR‐pQCT of two MTP joints could classify more patients with erosive RA compared with CR of 44 joints (p = .03). The optimal cut‐off value for the number and volume of erosions per patient in the 4th and 5th MTP joints by HR‐pQCT was 7.5 erosions and 11.7 mm3, respectively, for detecting erosive disease by CR. Erosions in the two MTP joints by HR‐pQCT were found most frequently and were largest at the lateral quadrant of the 5th metatarsal head.

Conclusion

The superiority of HR‐pQCT of the 4th and 5th MTP joints compared with CR of 44 joints for classifying erosive RA provides a basis for larger studies evaluating if HR‐pQCT could be used for diagnosing erosive RA in the future.
Cancer development in patients hospitalized with systemic lupus erythematosus: A population‐level data linkage study
Authors: Raymond Warren David , Preen David Brian , Keen Helen Isobel , Inderjeeth Charles Anoopkumar , Nossent Johannes Cornelis
Published: June 2023

Aim

To explore the association between systemic lupus erythematosus (SLE) with the risk of cancer development and subsequent 5‐year mortality in Western Australia (WA).

Methods

Population‐level, data linkage study of SLE patients (n = 2111) and general population comparators (n = 21 110) hospitalized between 1980 and 2014. SLE patients (identified by ICD‐9‐CM: 695.4, 710.0, and ICD‐10‐AM: L93.0, M32.0) were nearest matched (10:1) for age, sex, Aboriginality, and temporality. Follow up was from time zero (index SLE hospitalization) to cancer development, death or 31 December 2014. We assessed the risk of cancer development and subsequent 5‐year mortality between SLE patients and comparators with univariate and multivariate‐adjusted Cox proportional hazards regression models.

Results

SLE patients had similar multivariate‐adjusted risk (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.93–1.15; p = .583) of cancer development. Cancer development risk was higher in SLE patients <40 years old (aHR 1.58, 95% CI 1.29–1.94; p < .001), and from 1980 to 1999 (aHR 1.16, 95% CI 1.02–1.31; p < .001). SLE patients had higher risk of developing cancer of the oropharynx (aHR 2.13, 95% CI 1.30–3.50), vulvo‐vagina (aHR 3.22, 95% CI 1.34–7.75), skin (aHR 1.20, 95% CI 1.01–1.43), musculoskeletal tissues (aHR 2.26, 95% CI 1.16–4.40), and hematological tissues (aHR 1.78 95% CI 1.25–2.53), all p < .05. After cancer development, SLE patients had increased risk of 5‐year mortality (aHR 1.31, 95% CI 1.06–1.61); highest in patients <50 years old (aHR 2.03, 95% CI 1.03–4.00), and in those with reproductive system and skin cancers.

Conclusions

Hospitalized SLE patients had increased risk of multiple cancer sub‐types. Following cancer development, SLE patients had increased risk of 5‐year mortality. There is scope to improve cancer prevention and surveillance in SLE patients.

Trial registration

Not applicable. This low‐risk risk study used de‐identified administrative linked health data.
Acute myeloid leukemia and myelodysplastic syndrome associated with a combination of immune checkpoint inhibitor and platinum‐based chemotherapy
Authors: Nakatsuru Kousei , Tsubouchi Kazuya , Hirahata Minori , Nakashima Tadayuki , Takahata Yuriko , Okamatsu Yuki , Shiraishi Yoshimasa , Okamoto Isamu , Harada Taishi
Published: June 2023

Therapy related‐acute myeloid leukemia (t‐AML) and myelodysplastic syndrome (t‐MDS) are complications of chemotherapy and/or radiation therapy for malignant diseases. In this report, we describe a patient with advanced lung adenocarcinoma who developed autoimmune hemolytic anemia and MDS associated with a combination of atezolizumab and platinum‐based chemotherapy. The patient showed progression from t‐MDS to t‐AML 20 months after the treatment was initiated. A combination of immune checkpoint inhibitor (ICI) and chemotherapy may increase the risk of developing therapy‐related myeloid neoplasms. As the prognosis of t‐AML and t‐MDS is poorer than that of de novo AML and MDS, proper surveillance, follow‐up, and treatment are needed throughout the course of immunotherapy.
The implications of firms' derivative usage on the frequency and usefulness of management earnings forecasts
Authors: Campbell John L. , Cao Sean Shun , Chang Hye Sun , Chiorean Raluca
Published: June 2023

We investigate how firms' use of derivatives impacts voluntary disclosure and offer four main findings. First, we find that when firms begin using derivative instruments, they increase the frequency of management earnings forecasts. Second, using path analysis, we find a direct link between derivative usage and forecast frequency, as well as an indirect link through reduced earnings volatility. Third, we find that CEOs with more pronounced career concerns increase forecast frequency only when derivatives make earnings easier to forecast and find no evidence that investor demand drives the decision to provide a forecast. These results suggest that the primary mechanism for the association between derivative usage and forecast frequency is a reduction in the manager's costs of providing the forecasts. Finally, we find that the majority of derivative‐induced forecasts are uninformative to capital market participants, especially after FAS 161 provided the necessary underlying data to understand how firms use derivatives. Overall, we provide the first empirical evidence that firms that use derivatives issue more management forecasts, but we also find that these incremental forecasts are largely uninformative and appear driven by managerial career concerns.
Multi‐animal‐model study reveals mutations in neural plasticity and nociception genes linked to excessive alcohol drinking
Authors: Muir William M. , Lo Chiao‐Ling , Bell Richard L. , Zhou Feng C.
Published: June 2023

Background

The basis for familial alcohol use disorder (AUD) remains an enigma due to various biological and societal confounds. The present study used three of the most adopted and documented rat models, combining the alcohol‐preferring/non‐alcohol‐preferring (P/NP) lines and high alcohol‐drinking/low alcohol‐drinking (HAD/LAD) replicated lines, of AUD as examined through the lens of whole genomic analyses.

Methods

We used complete genome sequencing of the P/NP lines and previously published sequences of the HAD/LAD replicates to enhance the discovery of variants associated with AUD and to remove confounding with genetic background and random genetic drift. Specifically, we used high‐order statistical methods to search for genetic variants whose frequency changes in whole sets of gene ontologies corresponded with phenotypic changes in the direction of selection, that is, ethanol‐drinking preference.

Results

Our first finding was that in addition to variants causing translational changes, the principal genetic changes associated with drinking predisposition were silent mutations and mutations in the 3′ untranslated regions (3′UTR) of genes. Neither of these types of mutations alters the amino acid sequence of the translated protein but they influence both the rate and conformation of gene transcription, including its stability and posttranslational events that alter gene efficacy. This finding argues for refocusing human genomic studies on changes in gene efficacy. Among the key ontologies identified were the central genes associated with the Na+ voltage–gated channels of neurons and glia (including the Scn1a, Scn2a, Scn2b, Scn3a, Scn7a, and Scn9a subtypes) and excitatory glutamatergic secretion (including Grm2 and Myo6), both of which are essential in neuroplasticity. In addition, we identified “Nociception or Sensory Perception of Pain,” which contained variants in nociception (Arrb1, Ccl3, Ephb1) and enlist sodium (Scn1a, Scn2a, Scn2b, Scn3a, Scn7a), pain activation (Scn9a), and potassium channel (Kcna1) genes.

Conclusion

The multi‐model analyses used herein reduced the confounding effects of random drift and the “founders” genetic background. The most differentiated bidirectionally selected genes across all three animal models were Scn9a, Scn1a, and Kcna, all of which are annotated in the nociception ontology. The complexity of neuroplasticity and nociception adds strength to the hypothesis that neuroplasticity and pain (physical or psychological) are prominent phenotypes genetically linked to the development of AUD.
Risk of suicide attempt and suicide associated with benzodiazepine: A nationwide case crossover study
Authors: Tournier Marie , Bénard‐Laribière Anne , Jollant Fabrice , Hucteau Emilie , Diop Papa‐Yatma , Jarne‐Munoz Ana , Pariente Antoine , Oger Emmanuel , Bezin Julien
Published: June 2023

Background

Previous studies that found an association between benzodiazepines and suicidal behaviours were confounded by indication bias.

Aims

To limit this bias, a case crossover study (CCO) was conducted to estimate the risk of suicide attempt and suicide associated with benzodiazepines.

Method

Patients ≥16 years, with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act were selected in the nationwide French reimbursement healthcare system databases (SNDS). For each patient, frequency of benzodiazepine dispensing was compared between a risk period (days −30 to −1 before the event) and two matched reference periods (days −120 to −91, and −90 to −61).

Results

A total of 111,550 individuals who attempted suicide and 12,312 suicide victims were included, of who, respectively, 77,474 and 7958 had recent psychiatric history. Benzodiazepine dispensing appeared higher in the 30‐day risk period than in reference ones. The comparison yielded adjusted odds ratios of 1.74 for hospitalised suicide attempt (95% confidence interval 1.69–1.78) and 1.45 for suicide (1.34–1.57) in individuals with recent psychiatric history, and of 2.77 (2.69–2.86) and 1.80 (1.65–1.97) for individuals without.

Conclusion

This nationwide study supports an association between recent benzodiazepine use and both suicide attempt and suicide. These results strengthen the need for screening for suicidal risk carefully before initiation and during treatment when prescribing benzodiazepines. Registration No. EUPAS48070 (http://www.ENCEPP.eu).
Technology transmission in pre‐modern China: Evidence from a Chinese clan, 1400–1800
Authors: Wang Runnan
Published: June 2023

This study examines the intergenerational transmission of technology in historical China by constructing a genealogy dataset of the Huang family from 1400 to 1800. The family specialised in woodblock carving for book production, and their names were documented in these volumes, enabling measurement of technological output. Analysing 902 individuals across 16 generations reveals that carving skills were primarily transmitted from fathers to sons, with little influence from other family members or external artisans. Moreover, the production of books by the Huang family experienced a decline in the early 17th century, potentially attributed to weather shocks and decreased demand for books.
Genetic polymorphism and variability in the Guangdong Hakka, Teochew, and Cantonese groups: A comprehensive analysis of 19 X‐STRs
Authors: Xiao Cheng , Yang Xingyi , Yu Zhonghao , Wu Weibin , Wang Yuan , Xu Quyi , Chen Ling
Published: June 2023

Background

X chromosomeshort tandem repeat (X‐STR) loci are playing an increasingly important role inforensic work, identifying female traces in male contamination and explainingcomplex kinship analyses.

Methods

In this study, we analyzed thegenetic polymorphism of 19 X‐STR loci in the Guangdong Hakka, Teochew and Cantonese groups, respectively, aswell as in the Guangdong Hakka, Teochew andCantonese pooled Han. The genetic diversity and forensic characteristics of the19 X‐STRs and 7 linkage groups were investigated, respectively.

Results

The experiments showed that the genetic diversity (GD) and polymorphism information content (PIC) in the pooledGuangdong Han ranged from 0.5320 to 0.9234 and 0.4369 to 0.9171, respectively, and the cumulative power of discrimination for males (PDM), power of discrimination for females (PDF) and mean paternity exclusion chance (MEC) were higher than 0.9999999, indicating that the 19 X‐STRs had high geneticpolymorphism and discriminatory power. Genetic differences among Chinese Hansubgroups and among different Chinese populations were investigated byphylogenetic reconstruction and principal component analysis (PCA), respectively. Genetic analyses based on neighbor‐joining (NJ) tree and principal component analysis plot showed that Cantonese, Teochew and Hakka were closely genetically related, and different populations with closer linguistic components had more genetic affinity.

Conclusions

This study adds to the forensic X‐STR database and demonstrates the forensic efficiency of 19 X‐STRs for the Hakka, Teochewand Cantonese populations in Guangdong, and the pooled Han of Hakka, Teochewand Cantonese people in Guangdong.
Promoter region variant C‐824T in the TH gene modulates the subjective effects of cocaine
Authors: Bolin Peter K. , Nielsen Ellen M. , Nielsen David A. , De La Garza Richard
Published: June 2023

Background and Objectives

This study examined how a promoter variant of TH (rs10770141) affects subjective effects of cocaine in 65 nontreatment‐seeking individuals with cocaine dependence.

Methods

Participants received cocaine/saline intravenously, and TH genotypes were evaluated.

Results

Homozygous individuals for the minor T allele reported greater “good” and “bad” subjective effects to cocaine than those with the major C allele.

Discussion and Conclusions

TH rs10770141 modulates subjective effects of cocaine in participants with cocaine dependence.

Scientific Significance

These results are among the first to indicate that homozygosity of the T allele of rs10770141 modulates greater sensitivity to cocaine.
Is Spain Different? The Tamed Memory of the Spanish Civil War and the Limits of Spain's National Self‐Image (2008–10)
Authors: Huys David
Published: June 2023

This article focusses on ongoing discussions about the place of the Spanish Civil War (1936–39) and the Franco dictatorship (1939–75) in Spain's democracy. Following the suspension of Judge Baltasar Garzón by the Spanish Supreme Court in 2010, who had indicted General Francisco Franco (1892–1975) and thirty‐four accomplices under international law for committing crimes against humanity, a debate arose between leading intellectuals in Spain about the growing international influence on Spain's war past. This debate revealed that a group of influential left‐wing intellectuals attempted to curb the social and political influence of the citizens' memory movements. The author observes how this happened by applying three strategies: the foreign strategy, the nationalistic‐ethical strategy, and the saturation strategy. He concludes that the growing international pressure on Spain's handling of the Civil War and dictatorship led to a “Spanification” of the “culture of the transición” as a national memory, causing the memory movements to lose momentum and curbing the international influence on Spain's handling of its dictatorial past.
Timing of elective surgery and risk assessment after SARS‐CoV‐2 infection: 2023 update
Authors: El‐Boghdadly K. , Cook T. M. , Goodacre T. , Kua J. , Denmark S. , Mercer N. , Moonesinghe S. R. , Summerton D. J.
Published: June 2023

Guidance for the timing of surgery following SARS‐CoV‐2 infection needed reassessment given widespread vaccination, less virulent variants, contemporary evidence and a need to increase access to safe surgery. We, therefore, updated previous recommendations to assist policymakers, administrative staff, clinicians and, most importantly, patients. Patients who develop symptoms of SARS‐CoV‐2 infection within 7 weeks of planned surgery, including on the day of surgery, should be screened for SARS‐CoV‐2. Elective surgery should not usually be undertaken within 2 weeks of diagnosis of SARS‐CoV‐2 infection. For patients who have recovered from SARS‐CoV‐2 infection and who are low risk or having low‐risk surgery, most elective surgery can proceed 2 weeks following a SARS‐CoV‐2 positive test. For patients who are not low risk or having anything other than low‐risk surgery between 2 and 7 weeks following infection, an individual risk assessment must be performed. This should consider: patient factors (age; comorbid and functional status); infection factors (severity; ongoing symptoms; vaccination); and surgical factors (clinical priority; risk of disease progression; grade of surgery). This assessment should include the use of an objective and validated risk prediction tool and shared decision‐making, taking into account the patient's own attitude to risk. In most circumstances, surgery should proceed unless risk assessment indicates that the risk of proceeding exceeds the risk of delay. There is currently no evidence to support delaying surgery beyond 7 weeks for patients who have fully recovered from or have had mild SARS‐CoV‐2 infection.
Flame thrower
Authors: Vidali Debra
Published: June 2023

This poem is part of a special section in honor of Kathleen Stewart. Imagined as a staccato spoken word piece, the short lines with visual semantic and sonic parallelisms flow like an urgent, nonstop process of throwing flames, barbs, disruptions, and unexpected care into anthropological spaces. As such, the poetic layout pays tribute with an itemized list of Katie's interventions: surgical strikes, sharp, powerful presences, and gentle lyric clarity.
Dialectical improv
Authors: Causey Andrew
Published: June 2023

Part of a special section in honor of Kathleen Stewart, “Hundreds for Katie,” this piece compresses thirty years of interactions into a few pithy words to characterize one facet of the author's on‐going relationship with her.
Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study
Authors: Duan Hui , Li Huimin , Kang Shan , Zhao Hongwei , Chen Biliang , Wang Li , Li Pengfei , Wang Yahong , Wang Wei , Lang Jinghe , Liu Ping , Chen Chunlin
Published: June 2023

Introduction

FIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size.

Material and methods

We retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I–IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC‐T1, IIIC‐T2a, IIIC‐T2b, and IIIC‐(T3a+T3b). Oncologcial outcomes of all stages were compared.

Results

A total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan–Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC‐(T1‐T2b) was significantly better than of IIIA+IIIB and IIIC‐(T3a+T3b); no significant difference was noted between IIB and IIIC‐(T1‐T2b), or IIIC‐(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC‐T1, Stages T2a, T2b, IIIA+IIIB and IIIC‐(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC‐(T1‐T2b) and IIB. Also, compared with IIB, IIIC‐(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC‐(T3a+T3b) and IIIA+IIIB.

Conclusions

In terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC‐T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.
Symptoms mediate the relationship between childhood trauma and non‐suicidal self‐injury: A hospital‐based study of adolescents with mood disorder
Authors: Zhou Rui , Ji Ting , Zhang Ji‐Jie , Liu Yin‐Du , Wang Fei , Jia Fu‐Jun , Hou Cai‐Lan
Published: June 2023

Background

Childhood trauma has a significant impact on the development of adolescents, which may lead to interpersonal and psychological problems. Determining the incidence and consequences of childhood trauma in psychiatric clinical practice is of great significance.

Methods

A survey was conducted among adolescents with mood disorders. Childhood Trauma Questionnaire (CTQ), the Adolescent Non‐Suicidal‐Self‐Injury Behavior Function Assessment Scale (ANBFAS) and a series of psychological scales were filled face to face. Path analysis was used to examine the causation structure of childhood trauma‐related symptoms.

Results

A total of 117 participants (74.5%) had experienced at least one type of trauma. Interpersonal and psychological features of adolescent patients with childhood trauma were detailed in this study. The path analysis model showed that the relationships between childhood trauma and NSSI were mediated by depressive symptoms and thinking disorders, respectively, whereas depressive symptoms individually mediated the correlation between childhood trauma and sleep disturbances in adolescent patients with psychiatric disorders (χ2/df = 1.23).

Conclusion

For adolescent patients with childhood trauma, psychological counseling for interpersonal relationships should start with families and peers. It is important to treat their depressive symptoms and thinking disorders and alleviate NSSI behavior and sleep disorders.
Generation and initial characterization of mice lacking full‐length BAI3 (ADGRB3) expression
Authors: Shiu Fu Hung , Wong Jennifer C. , Bhattacharya Debanjan , Kuranaga Yuki , Parag Rashed R. , Alsharif Haifa A. , Bhatnagar Sushant , Van Meir Erwin G. , Escayg Andrew
Published: June 2023

Brain‐specific angiogenesis inhibitor 3 (ADGRB3/BAI3) belongs to the family of adhesion G protein‐coupled receptors. It is most highly expressed in the brain where it plays a role in synaptogenesis and synapse maintenance. Genome‐wide association studies have implicated ADGRB3 in disorders such as schizophrenia and epilepsy. Somatic mutations in ADGRB3 have also been identified in cancer. To better understand the in vivo physiological role of ADGRB3, we used CRISPR/Cas9 editing to generate a mouse line with a 7‐base pair deletion in Adgrb3 exon 10. Western blot analysis confirmed that homozygous mutants (Adgrb3∆7/∆7) lack full‐length ADGRB3 expression. The mutant mice were viable and reproduced in Mendelian ratios but demonstrated reduced brain and body weights and deficits in social interaction. Measurements of locomotor function, olfaction, anxiety levels and prepulse inhibition were comparable between heterozygous and homozygous mutants and wild‐type littermates. Since ADGRB3 is also expressed in organs such as lung and pancreas, this new mouse model will facilitate elucidation of ADGRB3's role in non‐central nervous system‐related functions. Finally, since somatic mutations in ADGRB3 were identified in patients with several cancer types, these mice can be used to determine whether loss of ADGRB3 function contributes to tumour development.
Conditional Inference in Cis-Mendelian Randomization Using Weak Genetic Factors
Authors: Patel Ashish , Gill Dipender , Newcombe Paul , Burgess Stephen
Published: June 2023

Mendelian randomization (MR) is a widely used method to estimate the causal effect of an exposure on an outcome by using genetic variants as instrumental variables. MR analyses that use variants from only a single genetic region (cis-MR) encoding the protein target of a drug are able to provide supporting evidence for drug target validation. This paper proposes methods for cis-MR inference that use many correlated variants to make robust inferences even in situations, where those variants have only weak effects on the exposure. In particular, we exploit the highly structured nature of genetic correlations in single gene regions to reduce the dimension of genetic variants using factor analysis. These genetic factors are then used as instrumental variables to construct tests for the causal effect of interest. Since these factors may often be weakly associated with the exposure, size distortions of standard t-tests can be severe. Therefore, we consider two approaches based on conditional testing. First, we extend results of commonly-used identification-robust tests for the setting where estimated factors are used as instruments. Second, we propose a test which appropriately adjusts for first-stage screening of genetic factors based on their relevance. Our empirical results provide genetic evidence to validate cholesterol-lowering drug targets aimed at preventing coronary heart disease.
Lessons from the deep: mechanisms behind diversification of eukaryotic protein complexes
Authors: Prokopchuk Galina , Butenko Anzhelika , Dacks Joel B. , Speijer Dave , Field Mark C. , Lukeš Julius
Published: June 2023

Genetic variation is the major mechanism behind adaptation and evolutionary change. As most proteins operate through interactions with other proteins, changes in protein complex composition and subunit sequence provide potentially new functions. Comparative genomics can reveal expansions, losses and sequence divergence within protein‐coding genes, but in silico analysis cannot detect subunit substitutions or replacements of entire protein complexes. Insights into these fundamental evolutionary processes require broad and extensive comparative analyses, from both in silico and experimental evidence. Here, we combine data from both approaches and consider the gamut of possible protein complex compositional changes that arise during evolution, citing examples of complete conservation to partial and total replacement by functional analogues. We focus in part on complexes in trypanosomes as they represent one of the better studied non‐animal/non‐fungal lineages, but extend insights across the eukaryotes by extensive comparative genomic analysis. We argue that gene loss plays an important role in diversification of protein complexes and hence enhancement of eukaryotic diversity.
Twenty‐nail dystrophy and alopecia areata in an adult male with thymoma‐associated myasthenia gravis: A case report
Authors: Prado Mario B. , Quinio Maria Franchesca , Adiao Karen Joy B.
Published: June 2023

Background

To date, there is no journal that reports the coexistence of thymoma‐associated myasthenia gravis, alopecia areata, and twenty‐nail dystrophy. This paper hypothesizes that the presence of thymoma increases the risk of these conditions.

Case presentation

The patient was a 37‐year‐old Filipino who came in for a year of history of fluctuating, but progressive, left‐sided ptosis and diplopia; difficulty swallowing; dysarthria; and aspiration and symmetric proximal muscle weakness confirmed to be myasthenia gravis by abnormal repetitive nerve stimulation and the presence of thymoma on histology. Before his thymectomy, he also developed gradually worsening thinning and longitudinal ridging of all fingernails and toenails; and patches of bald areas on the scalp; diagnosed to be twenty‐nail dystrophy and alopecia areata, respectively, by a board‐certified dermatologist.

Conclusion

Thymoma is the possible risk factor and link for the co‐occurrence of the three conditions in the present patient.
Featured Cover
Authors: Zhao Chong , Qian Shuaijie , Tai Yang , Guo Yangkun , Tang Chengwei , Huang Zhiyin , Gao Jinhang
Published: June 2023

The cover image is based on the Original Article Proangiogenic role of circRNA‐007371 in liver fibrosis by Chong Zhao et al., https://doi.org/10.1111/cpr.13432.

image
Of Mojave milkweed and mirrors: The population genomic structure of a species impacted by solar energy development
Authors: Wade Miranda J. , Moore‐O'Leary Kara , Grodsky Steven M. , Hernandez Rebecca R. , Meek Mariah H.
Published: June 2023

A rapid renewable energy transition has facilitated the development of large, ground‐mounted solar energy facilities worldwide. Deserts, and other sensitive aridland ecosystems, are the second most common land‐cover type for solar energy development globally. Thus, it is necessary to understand existing diversity within environmentally sensitive desert plant populations to understand spatiotemporal effects of solar energy siting and design. Overall, few population genomic studies of desert plants exist, and much of their biology is unknown. To help fill this knowledge gap, we sampled Mojave milkweed (Asclepias nyctaginifolia) in and around the Ivanpah Solar Electric Generating Station (ISEGS) in the Mojave Desert of California to understand the species' population structure, standing genetic variation, and how that intersects with solar development. We performed Restriction‐site Associated Sequencing (RADseq) and discovered 9942 single nucleotide polymorphisms (SNPs). Using these data, we found clear population structure over small spatial scales, suggesting each site sampled comprised a genetically distinct population of Mojave milkweed. While mowing, in lieu of blading, the vegetation across the solar energy facility's footprint prevented the immediate loss of the ISEGS Mojave milkweed population, we show that the effects of land‐cover change, especially those impacting desert washes, may impact long‐term genetic diversity and persistence. Potential implications of this include a risk of overall loss of genetic diversity, or even hastened extirpation. These findings highlight the need to consider the genetic diversity of impacted species when predicting the impact and necessary conservation measures of large‐scale land‐cover changes on species with small population sizes.
Systemische Behandlung von Patienten mit Psoriasis in der täglichen Praxis: Eine retrospektive Studie auf Basis deutscher Krankenkassendaten
Authors: Heidbrede Tanja , Mevius Antje , Kessel Sebastian , Wilke Thomas , Maywald Ulf , Thiem Alexander
Published: June 2023

Hintergrund und Ziele

Psoriasis ist eine weit verbreitete Hauterkrankung, die für die Patienten eine große physische und psychische Belastung darstellt. Bis zu 30% der Patienten sind Kandidaten für eine systemische Behandlung. Ziel dieser Studie war es, die Merkmale und die systemische Behandlung von Psoriasis‐Patienten in der klinischen Praxis zu beschreiben.

Patienten und Methodik

Diese Studie basierte auf deutschen Krankenkassendaten. In einer Querschnittsanalyse wurden alle Psoriasis‐Patienten im Jahr 2020 beobachtet. In einer Längsschnittanalyse wurden Psoriasis‐Patienten betrachtet, die neu mit einer systemischen Behandlung begonnen haben.

Ergebnisse

Insgesamt wurden 116 507 vordiagnostizierte Psoriasis‐Patienten und 13 449 neu behandelte Patienten beobachtet. Von allen prävalenten Patienten erhielten 15,2% im Jahr 2020 eine systemische Behandlung (8,7% systemische Kortikosteroide). Von den neu behandelten Patienten begannen 95,2% mit einer konventionellen Behandlung (79,2% systemische Kortikosteroide), 4,0% mit Biologika und 0,9% mit Apremilast. Die Rate der Behandlungsabbrüche/‐wechsel nach einem Jahr war bei Kortikosteroiden am höchsten (91,3%) und bei Biologika am niedrigsten (23,1%).

Schlussfolgerungen

Etwa 15% der Psoriasis‐Patienten in Deutschland erhielten eine systemische Behandlung, davon wurden > 50% systemische Kortikosteroide verschrieben. Daraus schließen wir, dass die systemische Behandlung bei einer beträchtlichen Anzahl der beobachteten Patienten nicht den Leitlinienempfehlungen entspricht. Die niedrigsten Abbruch‐/Wechselraten bei Biologika sprechen für deren breiteren Einsatz.
Safety/tolerability, efficacy and pharmacokinetics of 600‐μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher: A phase I, randomized, double‐blind, placebo‐controlled study
Authors: Asano Michiko , Sekikawa Akiko , Sugeno Masatoshi , Matsuoka Osamu , Robertson Darren , Hansen Lars
Published: June 2023

Aim

To assess the safety/tolerability, efficacy and pharmacokinetics of once‐daily, 600‐μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher.

Materials and Methods

This phase I, randomized, double‐blind, placebo‐controlled study (NCT04208620) enrolled patients to receive subcutaneous cotadutide at an escalating dose to determine the highest tolerated clinical dose (Cohort 1), then applied in Cohort 2. The primary endpoint was safety, including treatment‐emergent adverse events (TEAEs); secondary endpoints included glycaemic control and body weight.

Results

Sixteen patients were randomly allocated to receive cotadutide or placebo in a 3:1 ratio. All patients were Asian, 62.5% were male, and the median age and body mass index were 60 years and 27.2 kg/m2, respectively. Through the follow‐up period of the study, 11/12 (91.7%) patients in the cotadutide group experienced a TEAE versus 1/4 (25.0%) patients in the placebo group. All TEAEs were mild, except for one moderate event. There were no deaths, serious TEAEs or TEAEs leading to study discontinuation. Gastrointestinal‐related events were the most common TEAEs. Cotadutide‐treated patients achieved significantly improved 7‐day mean glucose measured by continuous glucose monitoring; the 7‐day mean (standard deviation) at the end of treatment (day 70) was 112.23 (20.79) versus 206.85 (3.62) mg/dL for placebo. Mean respective changes in HbA1c were −1.13% (0.64%) and −0.17% (0.65%); and mean percentage changes in body weight were −6.93% (3.44%) and −1.23% (1.20%).

Conclusions

Cotadutide was well tolerated at doses up to 600 μg; efficacy versus placebo for weight loss and glycaemic control was shown.
Assessment of the patient with heart failure symptoms and risk factors: A guide for the non‐cardiologist
Authors: Arnold Suzanne V.
Published: June 2023

Although the prevalence of heart failure has been increasing over time, the presentation of heart failure has been shifting, with a greater proportion of preserved ejection fraction and more slowly progressive symptoms that require recognition in the outpatient setting. These shifts have placed more of the diagnostic responsibility onto primary care physicians, who often are challenged to determine the etiology of common symptoms in patients who often have several other potential reasons for these symptoms. Establishing a diagnosis of heart failure requires a step‐wise approach that includes physical exam (looking for multiple signs of hypervolemia), labs (B‐type natriuretic peptide levels), and echocardiography (structural and functional measures). Diagnostic algorithms are particularly challenging in patients with obesity, which limits the assessment of intravascular volume on exam, the quality of cardiac imaging, and the diagnostic accuracy of B‐type natriuretic peptide levels, which may be falsely low. In these challenging patients, the use of risk scores, invasive testing of intravascular volume, or empiric treatment of hypervolemia may be needed to determine whether symptoms are due to heart failure. Once a diagnosis of heart failure is established, several treatments can be beneficial, from diuretics to relieve congestion to various aspects of guideline‐directed medical therapy, some of which vary according to the ejection fraction of the patient. In addition, a diagnosis of heart failure may alter the treatment plan for comorbidities, including selection of anti‐hypertensive and glucose‐lowering medications, and medical or surgical treatments for obesity. While a diagnosis of heart failure may be challenging in many patients with slowly progressive and non‐specific symptoms, early recognition and treatment can be extremely effective at preventing hospitalizations, prolonging survival, and improving quality of life.
Instruments to assess students’ critical thinking—A qualitative approach
Authors: Paul Jomon A. , Sinha Mona , Cochran Justin D.
Published: June 2023

Critical thinking (CT) skills are essential to academic and professional success. Instruments to assess CT often rely on multiple‐choice formats with inherent problems. This research presents two instruments for assessing CT, an essay and open‐ended group‐discussion format, which were implemented in an undergraduate business course at a large public university. The topics were intentionally chosen to be digitally‐related (internet access and social media) since they raise complex issues, are applicable in many disciplines, and students are avid users, thereby making these instruments relevant, multidisciplinary, engaging, and multifaceted. These instruments may be adapted to enable educators to effectively assess undergraduate students’ ability to think critically. Qualitative analysis of the verbatim data with NVivo helps demonstrate the instruments’ efficacy in assessing CT, with (1) high‐quality responses receiving high grades, and (2) overarching themes identified by content analysis, that coalesce into the three dimensions of social justice theory (distributive, procedural, and interactional), thus illustrating students’ consideration of complex fairness norms and societal needs. Excerpts of student responses are provided as illustrations of the indicators/evidence of critical thinking. Educators can use these instruments to first assess students’ CT skills, and then devise targeted interventions to improve the quality of students’ thought processes.
Mean species responses predict effects of environmental change on coexistence
Authors: De Laender Frederik , Carpentier Camille , Carletti Timoteo , Song Chuliang , Rumschlag Samantha L. , Mahon Michael B. , Simonin Marie , Meszéna Géza , Barabás György
Published: June 2023

Environmental change research is plagued by the curse of dimensionality: the number of communities at risk and the number of environmental drivers are both large. This raises the pressing question if a general understanding of ecological effects is achievable. Here, we show evidence that this is indeed possible. Using theoretical and simulation‐based evidence for bi‐ and tritrophic communities, we show that environmental change effects on coexistence are proportional to mean species responses and depend on how trophic levels on average interact prior to environmental change. We then benchmark our findings using relevant cases of environmental change, showing that means of temperature optima and of species sensitivities to pollution predict concomitant effects on coexistence. Finally, we demonstrate how to apply our theory to the analysis of field data, finding support for effects of land use change on coexistence in natural invertebrate communities.
Regional cerebral perfusion during the premonitory phase of triggered migraine: A double‐blind randomized placebo‐controlled functional imaging study using pseudo‐continuous arterial spin labeling
Authors: Karsan Nazia , Bose Ray Pyari , O'Daly Owen , Zelaya Fernando , Goadsby Peter J.
Published: June 2023

Objective

To identify changes in regional cerebral blood flow (CBF) associated with premonitory symptoms (PS) of nitroglycerin (NTG)‐triggered migraine attacks.

Background

PS could provide insights into attack initiation and alterations in neuronal function prior to headache onset.

Methods

We undertook a functional imaging study using a double‐blind placebo‐controlled randomized approach in patients with migraine who spontaneously experienced PS, and in whom PS and migraine‐like headache could be induced by administration of NTG. All study visits took place in a dedicated clinical research facility housing a monitoring area with clinical beds next to a 3Tesla magnetic resonance imaging scanner. Fifty‐three patients with migraine were enrolled; imaging on at least one triggered visit was obtained from 25 patients, with 21 patients completing the entire imaging protocol including a placebo visit. Whole brain CBF maps were acquired using 3D pseudo‐continuous arterial spin labeling (3D pCASL).

Results

The primary outcome was that patients with migraine not taking preventive treatment (n = 12) displayed significant increases in CBF in anterior cingulate cortex, caudate, midbrain, lentiform, amygdala and hippocampus (p < 0.05 family‐wise error‐corrected) during NTG‐induced PS. A separate region of interest analysis revealed significant CBF increases in the region of the hypothalamus (p = 0.006, effect size 0.77). Post hoc analyses revealed significant reductions in CBF over the occipital cortices in participants with a history of migraine with underlying aura (n = 14).

Conclusions

We identified significant regional CBF changes associated with NTG‐induced PS, consistent with other investigations and with novel findings, withstanding statistical comparison against placebo. These findings were not present in patients who continually took preventive medication. Additional findings were identified only in participants who experience migraine with aura. Understanding this biological and treatment‐related heterogeneity is vital to evaluating functional imaging outcomes in migraine research.
Research on crack mechanism and kinetic model of alumina ceramic in the degreasing stage based on stereolithography
Authors: Cui Maomao , Wang Tao , Zhao Yi , Zhang Zhao , Wang Xiao , Hou Xin , Sun Wenxiang , Liu Huixia
Published: June 2023

Given that the kinetics of the thermal degreasing process of alumina ceramics based on stereolithography apparatus (SLA) has not been investigated, the mechanism of crack generation is still not fully revealed. This paper aims to elucidate the mechanism of crack generation in the degreasing process of alumina ceramics and to establish a kinetic model for alumina ceramics. Two sintering atmospheres, air, and argon, were selected for the degreasing tests at 100°C–700°C. The reaction products and mass changes of alumina ceramics were analyzed by TG‐FTIR and TG‐DSC (heating rates of 5, 10, and 15°C/min, respectively). Meanwhile, Boswell, Friedman, Ozawa, and DAEM model was used to describe the nonisothermal kinetics of the SLA alumina ceramic degreasing process. The results showed that setting the holding time to 400°C–425°C could promote the slow release of heat from the alumina ceramics. The thermal degreasing stage of the ceramic generated fewer cracks in the argon atmosphere than in the air atmosphere. The corresponding average activation energy values were 105.40 kJ/mol (Boswell model), 112.48 kJ/mol (Friedman model), 108.14 kJ/mol (Ozawa model), and 101.36 kJ/mol (DAEM model). The results of the study could provide an invaluable reference for the fabrication of defect‐free SLA alumina ceramics.
A paradox‐constitutive perspective of organizational gossip
Authors: Greenslade‐Yeats James , Cooper‐Thomas Helena , Corner Patricia D. , Morrison Rachel
Published: June 2023

We review cross‐disciplinary research on gossip and integrate it with two streams of theoretical scholarship: paradox theory and the communicative constitution of organization (CCO) perspective. In doing so, we develop what we label a paradox‐constitutive perspective of organizational gossip. Our perspective holds that gossip does not merely reflect or reveal organizational paradoxes but contributes to constituting them. Drawing on an extensive narrative literature review (N = 184), we conceptualize organizational gossip as a socially constructed category of interpersonal communication that, paradoxically, is regarded as both an exceptionally reliable and exceptionally unreliable source of social information. In turn, we illustrate how this contradictory view of gossip engenders paradoxical tensions when gossip surfaces in organizational life, and we illuminate two specific tensions to which gossip contributes: resistance‐authority tensions and inclusion‐exclusion tensions. Our work has important implications for research on organizational gossip, paradox, and communication and suggests intriguing directions for future investigations.
Comparison of wound complications between one‐stage and two‐stage brachiobasilic arteriovenous fistula: A meta‐analysis
Authors: Lu Yanyan , Xiao Jiao , Liu Chunyan , Wang Yuan
Published: June 2023

Research assessing the outcome of brachiobasilic arteriovenous fistulas (BB‐AVF) after a one‐ and two‐stage technique was conducted. A strict review of the comprehensive literature up to May 2023 was carried out using four databases‐PubMed，Embase, Cochrane Library and web of science. Inclusion and exclusion criteria developed for the study were then applied to assess the quality of the literature, it was decided to review 12 interrelated studies.95% confidence intervals (Cl) and odds ratios (OR) were calculated using fixed effects models. The data were meta‐analysed using RevMan 5.3 software. The results showed that two‐stage technique with BB‐AVF reduced surgical site haematoma (SSH) formation, (OR, 2.28; 95% CI, 1.24–4.17, p = 0.008), and also reduced surgical site wound infection (SSWI) (OR, 1.86; 95% CI, 1.17–2.94, p = 0.008). There are, however, several small sample sizes in the selected studies for this meta‐analysis, so caution should be used when processing their values. There are more high‐quality studies with large sample sizes that should be considered for future meta‐analyses.