bluuebunny/crossref_metadata_2025_split huggingface dataset:
The naturally occurring GIP(1-30)NH2 is a GIP receptor agonist in humans
Authors: Krogh Liva S L , Henriksen Kristine , Stensen Signe , Skov-Jeppesen Kirsa , Bergmann Natasha C , Størling Joachim , Rosenkilde Mette M , Hartmann Bolette , Holst Jens J , Gasbjerg Lærke S , Knop Filip K 
Published: January 2023

Abstract

Objective
The gut hormone glucose-dependent insulinotropic polypeptide (GIP) is an important regulator of glucose and bone metabolism. In rodents, the naturally occurring GIP variant, GIP(1-30)NH2, has shown similar effects as full-length GIP (GIP(1-42)), but its effects in humans are unsettled. Here, we investigated the actions of GIP(1-30)NH2 compared to GIP(1-42) on glucose and bone metabolism in healthy men and in isolated human pancreatic islets.

Methods
Nine healthy men completed three separate three-step glucose clamps (0-60 minutes at fasting plasma glucose (FPG) level, 60-120 minutes at 1.5× FPG, and 120-180 minutes at 2× FPG) with infusion of GIP(1-42) (4 pmol/kg/min), GIP(1-30)NH2 (4 pmol/kg/min), and saline (9 mg/mL) in randomised order. Blood was sampled for measurement of relevant hormones and bone turnover markers. Human islets were incubated with low (2 mmol/L) or high (20 mmol/L) d-glucose with or without GIP(1-42) or GIP(1-30)NH2 in three different concentrations for 30 minutes, and secreted insulin and glucagon were measured.

Results
Plasma glucose (PG) levels at FPG, 1.5× FPG, and 2× FPG were obtained by infusion of 1.45 g/kg, 0.97 g/kg, and 0.6 g/kg of glucose during GIP(1-42), GIP(1-30)NH2, and saline, respectively (P = .18), and were similar on the three experimental days. Compared to placebo, GIP(1-30)NH2 resulted in similar glucagonotropic, insulinotropic, and carboxy-terminal type 1 collagen crosslinks-suppressing effects as GIP(1-42). In vitro experiments on human islets showed similar insulinotropic and glucagonotropic effects of the two GIP variants.

Conclusions
GIP(1-30)NH2 has similar effects on glucose and bone metabolism in healthy individuals and in human islets in vitro as GIP(1-42).
Lack of sensitivity of diagnostic Cushing-scores in Germany: a multicenter validation
Authors: Braun Leah T , Vogel Frederick , Rubinstein German , Zopp Stephanie , Nowak Elisabeth , Constantinescu Georgiana , Masjkur Jimmy , Detomas Mario , Pamporaki Christina , Altieri Barbara , Deutschbein Timo , Quinkler Marcus , Beuschlein Felix , Reincke Martin 
Published: January 2023

Abstract

Objective
Endogenous Cushing's syndrome (CS) is a severe condition, often diagnosed at a late stage. To reduce mortality, early diagnosis plays an important role. Two screening tools for early identification of patients with CS have been developed in multicentric cohorts, but have not yet been validated in cohorts with different geographic backgrounds.

Design
We validated the Spanish score published by Leon-Justel et al. in 2016 and the Italian score by Parasiliti-Caprino et al. published in 2021 in our cohort.

Methods
In the multicentric German Cushing registry, patients with confirmed and expected but ruled out Cushing's syndrome are prospectively diagnosed and followed up. We validated both scores in a cohort of 458 subjects: 176 patients with confirmed CS and 282 patients with suspected, but finally excluded CS.

Results
Using the Spanish score, 17.5% of our patients with proven CS biochemical screening would not have been recommended. This concerned patients with pituitary CS (22%) and with adrenal CS (10%). On the contrary, only 14% of patients without CS would have received a recommendation for biochemical screening. Using the Italian score, 29% of patients with proven CS were classified into the low-risk classes not recommended for biochemical screening. This mostly affected patients with adrenal (31%) and pituitary CS (30%). About 12% of subjects without CS would have received a biochemical screening recommendation.

Conclusions
Both scores had limited sensitivity and high specificity in a German validation cohort. Further research is necessary to develop a screening score, which is effective in different healthcare systems and ethnicities.
Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation
Authors: Schiffer Lina , Kempegowda Punith , Sitch Alice J , Adaway Joanne E , Shaheen Fozia , Ebbehoj Andreas , Singh Sumitabh , McTaggart Malcom P , O’Reilly Michael W , Prete Alessandro , Hawley James M , Keevil Brian G , Bancos Irina , Taylor Angela E , Arlt Wiebke 
Published: January 2023

Abstract

Objective
11-oxygenated androgens significantly contribute to the circulating androgen pool. Understanding the physiological variation of 11-oxygenated androgens and their determinants is essential for clinical interpretation, for example, in androgen excess conditions. We quantified classic and 11-oxygenated androgens in serum and saliva across the adult age and body mass index (BMI) range, also analyzing diurnal and menstrual cycle-dependent variation.

Design
Cross-sectional. Morning serum samples were collected from 290 healthy volunteers (125 men, 22-95 years; 165 women, 21-91 years). Morning saliva samples were collected by a sub-group (51 women and 32 men). Diurnal saliva profiles were collected by 13 men. Twelve women collected diurnal saliva profiles and morning saliva samples on 7 consecutive days during both follicular and luteal menstrual cycle phases.

Methods
Serum and salivary steroids were quantified by liquid chromatography–tandem mass spectrometry profiling assays.

Results
Serum classic androgens decreased with age-adjusted BMI, for example, %change kg/m2 for 5α-dihydrotestosterone: men −5.54% (95% confidence interval (CI) −8.10 to −2.98) and women −1.62% (95%CI −3.16 to −0.08). By contrast, 11-oxygenated androgens increased with BMI, for example, %change kg/m2 for 11-ketotestosterone: men 3.05% (95%CI 0.08-6.03) and women 1.68% (95%CI −0.44 to 3.79). Conversely, classic androgens decreased with age in both men and women, while 11-oxygenated androgens did not. Salivary androgens showed a diurnal pattern in men and in the follicular phase in women; in the luteal phase, only 11-oxygenated androgens showed diurnal variation.

Conclusions
Classic androgens decrease while active 11-oxygenated androgens increase with increasing BMI, pointing toward the importance of adipose tissue mass for the activation of 11-oxygenated androgens. Classic but not 11-oxygenated androgens decline with age.
Identifying strengths and weaknesses of methods for computational network inference from single-cell RNA-seq data
Authors: McCalla Sunnie Grace , Fotuhi Siahpirani Alireza , Li Jiaxin , Pyne Saptarshi , Stone Matthew , Periyasamy Viswesh , Shin Junha , Roy Sushmita 
Published: January 2023

Abstract
Single-cell RNA-sequencing (scRNA-seq) offers unparalleled insight into the transcriptional programs of different cellular states by measuring the transcriptome of thousands of individual cells. An emerging problem in the analysis of scRNA-seq is the inference of transcriptional gene regulatory networks and a number of methods with different learning frameworks have been developed to address this problem. Here, we present an expanded benchmarking study of eleven recent network inference methods on seven published scRNA-seq datasets in human, mouse, and yeast considering different types of gold standard networks and evaluation metrics. We evaluate methods based on their computing requirements as well as on their ability to recover the network structure. We find that, while most methods have a modest recovery of experimentally derived interactions based on global metrics such as Area Under the Precision Recall curve, methods are able to capture targets of regulators that are relevant to the system under study. Among the top performing methods that use only expression were SCENIC, PIDC, MERLIN or Correlation. Addition of prior biological knowledge and the estimation of transcription factor activities resulted in the best overall performance with the Inferelator and MERLIN methods that use prior knowledge outperforming methods that use expression alone. We found that imputation for network inference did not improve network inference accuracy and could be detrimental. Comparisons of inferred networks for comparable bulk conditions showed that the networks inferred from scRNA-seq datasets are often better or at par with the networks inferred from bulk datasets. Our analysis should be beneficial in selecting methods for network inference. At the same time, this highlights the need for improved methods and better gold standards for regulatory network inference from scRNAseq datasets.
Third-space endoscopy: the final frontier
Authors: Hayat Maham , Yang Dennis , Draganov Peter V 
Published: January 2023

Abstract
Over the years, our growing experience with endoscopic submucosal dissection along with technological advances has solidified our comfort and knowledge on working in the submucosa, also referred to as the “third space.” Per-oral endoscopic myotomy (POEM) was the first prototype third-space endoscopy (TSE) procedure, demonstrating the feasibility and clinical utility of endoscopic esophagogastric myotomy via submucosal tunneling. The launch of POEM accelerated the evolution of TSE from a vanguard concept to an expanding field with a wide range of clinical applications. In this review, we discuss the status and future directions of multiple TSE interventions.
Decrease in Gait Speed Over Time Is Associated With Increase in Number of Depression Symptoms in Older Adults With Type 2 Diabetes
Authors: Lavie Inbar , Schnaider Beeri Michal , Schwartz Yonathan , Soleimani Laili , Heymann Anthony , Azuri Joseph , Ravona-Springer Ramit 
Published: January 2023

Abstract

Background
We examined the cross-sectional and longitudinal relationships of motor functions with depression in older adults with type 2 diabetes (T2D).

Methods
Participants (n = 984) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of motor functions (grip strength and gait speed) and of depression (using the 15-item version of the Geriatric Depression Scale [GDS]) approximately every 18 months. We applied Hierarchical Linear Mixed Models (HLMM) to investigate the associations between motor functions and depression adjusting for sociodemographic, cardiovascular factors, overall cognitive score, and subjective report of exhaustion.

Results
Participants’ baseline characteristics were 72 (±5) years of age (59.6% males), 13 (±4) years of education, Mini-Mental Status Exam (MMSE) score of 28.01 (±1.78), and a GDS score of (2 ± 2.00), consistent with normal cognitive status and lack of major affective symptomatology. Slower gait speed at baseline was associated with higher GDS scores (p = .001) and with their increase over time (p = .049). A decrease in walking speed from baseline was associated with an increase in GDS scores (p = .015). Lower grip strength at baseline was associated with higher GDS scores (p = .002), but not with trajectories in GDS scores over time. A faster decrease in grip strength from baseline was associated with a faster increase in GDS scores (p = .022).

Conclusions
Both gait speed and grip strength are cross-sectionally associated with depression. However, only gait speed and its decrease over time can potentially be used to predict incident depression symptoms, thus facilitating the introduction of depression prevention strategies.
Different Sources of Sugar Consumption and Cognitive Performance in Older Adults: Data From the National Health and Nutrition Examination Survey 2011–2014
Authors: Gomes Gonçalves Natalia , Suemoto Claudia Kimie , Ferreira Naomi Vidal 
Published: January 2023

AbstractObjectivesExcess sugar consumption, particularly in sugar-sweetened beverages (SSBs), has been linked to poor cognitive performance. We aimed to assess the association of consumption of total sugar, as well as the consumption of SSBs, solid desserts, and 100% fruit juice with cognitive performance among older adults.MethodsConsumption of total sugar, SSBs, solid desserts, and 100% fruit juice were obtained from the 24-hr recall interview. Cognitive performance was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease word list, the Animal Fluency Test, and the Digit Symbol Substitution Test. Binary logistic regression models were used to evaluate the association between consumption of sugar (total and from different sources) and cognitive performance.ResultsA total of 1,938 participants aged 60 years or older from the National Health and Nutrition Examination Survey 2011–2014 were included. Compared to the lowest tertile, the highest tertile of total sugar consumption was independently associated with higher odds of low memory performance (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.00; 3.50, p = .049). Consumption of SSBs was associated with higher risk of low memory (OR = 1.58, 95% CI = 1.11; 2.25, p = .014), whereas consumption of solid desserts was associated with lower risk of low verbal fluency performance (OR = 0.62, 95% CI = 0.41; 0.95, p = .032).DiscussionHigher consumption of total sugars and SSBs was associated with lower memory performance, while consumption of solid desserts was associated with higher verbal fluency performance.
Reciprocal Relationship Between Lifelong Learning and Volunteering Among Older Adults
Authors: Sung Pildoo , Chia Arthur , Chan Angelique , Malhotra Rahul 
Published: January 2023

Abstract

Objectives
Lifelong learning and volunteering contribute to not only health and well-being, but also social inclusion and cohesion among older adults. However, less is known about whether lifelong learning and volunteering promote each other. This study examined the reciprocal relationship between older adults’ lifelong learning and volunteering and whether the relationship varied by the purpose of lifelong learning.

Methods
Cross-lagged panel models were applied to data on 2,608 older adults, aged 60 years and older, from 2 waves of a national longitudinal study from Singapore.

Results
We found a bidirectional relationship between lifelong learning and volunteering. However, when job-related and nonjob-related lifelong learning were considered separately, only nonjob-related lifelong learning predicted volunteering. On the other hand, volunteering predicted both job-related and nonjob-related lifelong learning.

Discussion
Lifelong learning leads to volunteering, and vice versa, creating a virtuous circle of productive social engagement in later life. Programs or initiatives engaging older adults in either productive activity should promote and provide opportunities for participation in the other activity.
The viscoacoustic Green's function for the Helmholtz equation in a velocity gradient interface model
Authors: Amundsen Lasse , Ursin Bjørn 
Published: January 2023

SUMMARYIn viscoacoustically stratified media where the density is constant, 3-D wave propagation in the frequency–radial wavenumber domain is governed by the Helmholtz equation. In the case that the model is a velocity gradient interface where the squared velocity in depth is represented by a smooth Heaviside function of the Fermi–Dirac distribution type, the Helmholtz equation for a point source at arbitrary location is shown to have analytical solution for the Green's function. The velocity depth profile, which is a modification of the Epstein profile which has been thoroughly studied in different branches of physics, is described by four parameters: the velocities at minus and plus infinity, the reference depth of the gradient interface, and its smoothness. The Helmholtz equation is first solved in a model where the point source is absent. The solution to the source-free equation has four unknown constants that must be determined. The radiation conditions at minus and plus infinity and two conditions on the Green's function at the source depth allow the constants to be found. The Green's function solution can be represented in two mathematically equivalent algebraic forms involving ordinary hypergeometric functions. The first form allows a numerically stable implementation over all wavenumber components. The second form allows a physical, intuitive interpretation and is expressed mathematically as the sum of two terms. Each of the terms contains the product of constant-velocity reference phase shift functions and hypergeometric functions which take the role to adjust the amplitude and phase shift calculated by the reference phase shift functions to account for the depth varying velocity profile. Inverse Fourier transforms take the Green's function from the frequency–wavenumber domain to the frequency–space domain or time–space domain. The Green's function solution is valid for any sharpness of the interface. Selected numerical results are presented for the 1-D and 2-D Helmholtz equation to demonstrate the influence of the velocity gradient zone on the wavefield. The 1-D solution in an acoustic model is compared in time domain to the classical finite-difference wave propagation solution. For the purpose of interpretation of seismograms, we model for comparison the wavefield response in a model of two half-spaces in welded contact. For brevity, the latter model is referenced as the HS model.
Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study
Authors: Lin Wei-Chen , Tai Wei-Chen , Chang Chung-Hsin , Tu Chia-Hung , Feng I-Che , Shieh Ming-Jium , Chung Chen-Shuan , Yen Hsu-Heng , Chou Jen-Wei , Wong Jau-Min , Liu Yu-Hwa , Huang Tien-Yu , Chuang Chiao-Hsiung , Tsai Tzung-Jiun , Chiang Feng-Fan , Lu Chien-Yu , Hsu Wen-Hung , Yu Fang-Jung , Chao Te-Hsin , Wu Deng-Chyang , Ho Ai-Sheng , Lin Hung-Hsin , Feng Chun-Lung , Wu Keng-Liang , Wong Ming-Wun , Tung Chien-Chih , Lin Chun-Chi , Chen Chia-Chang , Hu Huang-Ming , Lu Lung-Sheng , Wang Huann-Sheng , Wu I-Chen , Kuo Hsin-Yu , Wu Jia-Feng , Yao Shih Hsiang , Ni Yen-Hsuan , Tang Shu-Lun , Chen Peng-Hsu , Wei Shu-Chen 
Published: January 2023

Abstract

Background
This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed.

Methods
Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry.

Results
Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn’s disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non–reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively.

Conclusions
The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.
Exploring the Nexus between Transitional Justice and Ecoterritorial Conflict Resolution: Time for an Ecoterritorial Turn in Transformative Transitional Justice?
Authors: Kerremans Sarah , Destrooper Tine 
Published: January 2023

ABSTRACT∞
This article explores the nexus between ecoterritorial conflict resolution and transformative transitional justice, against the background of (neo)extractivism and the Peruvian case of half a century of oil violence. Our argument is twofold. On the one hand, we argue that transitional justice can act as a conceptual and analytical lens to better understand and further (claims for) change while also countering the invisibilization of ecoterritorial struggles of Indigenous and local communities who resist the framing of their lives and ecosystems as sacrificable or disposable. On the other hand, we argue that reading ecoterritorial struggles through the lens of transitional justice also has implications for the paradigm itself. The article is rooted in the first author’s longstanding work with Indigenous communities in the Peruvian Amazon who engage with transitional justice discourses and practices as part of their struggle against oil violence.
Evaluation and control ofAlternaria alternatacausing leaf spot in soybean in Northeast China
Authors: Li Wenqi , Huang Wei , Zhou Jiangruihang , Wang Jiajun , Liu Jinxin , Li Yonggang 
Published: January 2023

AbstractAimThe aims of this study were to characterize the causal agent of soybean leaf spot and determine the pathogenicity of the pathogen to the main crops in Northeast China and detect the sensitivity of pathogens to the main chemical fungicides and the potted control effect.Methods and resultsIn 2020 and 2021, an uncommon leaf spot was observed in Harbin, Heilongjiang Province (125°42′-130°10′E, 44°04′-46°40′N), China. The pathogen can infect soybean leaves and cause leaf spot. We collected diseased soybean leaves and isolated four pathogen organisms, all of which were identified as Alternaria alternata through morphological and molecular identification. Koch's postulates were used to confirm pathogenicity. To the best of our knowledge, this is the first report on soybean leaf spot disease caused by A. alternata in northeast China. Moreover, A. alternata had a broad host range and caused leaf spot in most legumes. However, it did not infect medicated lentil (Dolicho Lablab L.) or tobacco (Nicotiana tabacum L.). Assessment of A. alternaria susceptibility to fungicides by spore germination method, isolates of A. alternata were most sensitive to flusilazole, with EC50 values of 0.0040–0.0053 μg ml−1. Through two pot experiments, the average control efficacy of 0.1 mg ml−1 flusilazole on soybean leaf spot caused by A. alternata was 80.7%.ConclusionsThe work reported that A. alternata is the pathogen organism that causes soybean leaf spot in northern China. The pathogen organism can infect a variety of leguminous plants. Considering the control cost and effect, flusilazole is more suitable for controlling leaf spot disease in the field, and benzoxystrobin can be used as an alternative fungicide.