bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers
Authors: Madan Ajay , Markison Stacy , Betz Stephen F. , Krasner Alan , Luo Rosa , Jochelson Theresa , Lickliter Jason , Struthers R. Scott 
Published: January 2022

Abstract
Purpose
Evaluate the pharmacodynamics, pharmacokinetics, and safety of paltusotine, an orally bioavailable, nonpeptide, somatostatin receptor subtype 2 (SST2) agonist being developed for the treatment of acromegaly and neuroendocrine tumors.

Methods
A randomized, double-blind, placebo-controlled, single center, single and multiple ascending dose phase 1 study was conducted in healthy male volunteers who received (i) single-dose of oral paltusotine 1.25, 2.5, 5, 10, and 20 mg (solution); and 40 and 60 mg (capsules) or (ii) multiple-dose oral paltusotine capsules once daily 5 mg (× 7 days), 10, 20, and 30 mg (× 10 days). Main outcome measures were pharmacodynamics (changes in growth hormone-releasing hormone [GHRH] stimulated growth hormone [GH] and insulin-like growth factor 1 [IGF-1]), pharmacokinetics, safety, and tolerability.

Results
Single-dose cohorts: n = 41 active, n = 14 placebo. Multiple-dose cohorts: n = 24 active, n = 12 placebo. Paltusotine was well tolerated, orally bioavailable, associated with increased plasma concentrations to doses up to 40 mg, and was eliminated with a half-life of approximately 30 h. Single-dose paltusotine 1.25 to 20 mg suppressed GHRH-stimulated GH secretion by 44% to 93% compared to 15% with placebo. Multiple-dose paltusotine 5 to 30 mg administered once daily for 10 days suppressed IGF-1 by 19% to 37% compared to an increase of 2.4% with placebo.

Conclusions
Paltusotine suppresses GH and IGF-1 in a dose-dependent fashion, with a safety profile similar to currently approved SST2 receptor ligands. Paltusotine is a promising once-daily oral nonpeptide SST2 agonist candidate for managing acromegaly and neuroendocrine tumors.

Trial registration
NCT03276858, registered September 8, 2017, retrospectively registered.
Balancing litterfall and decomposition in cacao agroforestry systems
Authors: Sari Rika Ratna , Rozendaal Danaë M. A. , Saputra Danny Dwi , Hairiah Kurniatun , Roshetko James M. , van Noordwijk Meine 
Published: January 2022

Abstract
Backgrounds and aims
Litter protects the underlying soil, depending on litterfall and decomposition, but dynamics of the standing litter stock in agroforestry systems remain poorly understood. We aimed to unravel effects of litter quality, temporal patterns, microclimate, and a possible home-field advantage (HFA) on standing litter dynamics across a land-use gradient.

Methods
We quantified litterfall, the standing litter stock, and microclimate during a year in (remnant) forest, cacao-based simple and complex agroforestry, cacao monocultures, and annual crops in a cacao producing area in Indonesia. We conducted a reciprocal litter transfer experiment, and tested decomposition rates of pruning residues. Standing litter stocks during the year were estimated from monthly litterfall and decomposition rates.

Results
Variation in litter quality influenced decomposition rates more strongly than variation in microclimate or HFA. Lower litter quality in complex agroforestry and in the cacao monoculture decreased the decay rate compared to simple agroforestry systems; mean litter residence time was over a year. Mixing high- and low-quality material in pruning residues modified the decomposition rate, soil C and N changes, offering options for targeted management of soil protection and nutrient release.

Conclusions
The seasonal patterns of litterfall and relatively slow decomposition rates supported permanence of the litter layer in all cacao production systems, protecting the underlying soil.
Life cycle inventory data for the Italian agri-food sector: background, sources and methodological aspects
Authors: Notarnicola B. , Tassielli G. , Renzulli P. A. , Di Capua R. , Saija G. , Salomone R. , Primerano P. , Petti L. , Raggi A. , Casolani N. , Strano A. , Mistretta M. 
Published: January 2022

Abstract
Purpose
For the development of any life cycle assessment study, the practitioner frequently integrates primary data collected on-field, with background data taken from various life cycle inventory databases which are part of most commercial LCA software packages. However, such data is often not generally applicable to all product systems since, especially concerning the agri-food sector, available datasets may not be fully representative of the site specificity of the food product under examination. In this context, the present work investigates the background, sources and methodological aspects that characterise the most known commercial databases containing agri-food data, with a focus on four agri-food supply chains (olive oil, wine, wheat products and citrus fruit), which represent an important asset for the Italian food sector.

Methods
Specifically, the paper entails a review of currently available LCI databases and their datasets with a twofold scope: firstly, to understand how agri-food data is modelled in these databases for a coherent and consistent representation of regional scenarios and to verify whether they are also suitable for the Italian context and, secondly, to identify and analyse useful and relevant methodological approaches implemented in the existing LCI databases when regional data are modelled.

Results
Based on the aforementioned review, it is possible to highlight some problems which may arise when developing an LCI pertaining to the four Italian agri-food supply chains, namely:
1. The need for specific inventory datasets to tackle the specificities of agri-food product systems.
2. The lack of datasets, within the existing DBs, related to the Italian context and to the abovementioned supply chains. In fact, at present, in the currently available LCI DBs, there are very few (or in some cases none) datasets related to Italian wine, olive oil, wheat-based products and citrus fruit. The few available datasets often contain some data related to the Italian context but also approximate data with that of product systems representing other countries.
Furthermore, the present study allowed to identify and discuss the main aspects to be used as starting elements for modelling regional data to be included in a future Italian LCI database of the abovementioned four supply chains.

Conclusions
The results of the present study represent a starting point for the collection of data and its organisation, in order to develop an Italian LCI agri-food database with datasets which are representative of the regional specificities of four agri-food supply chains which play an important role in the Italian economy.
Marketing control in international headquarters-subsidiary working relationships of industrial goods firms: the role of environmental context
Authors: Isenberg Lukas , Kreiter Susanne , Helm Roland , Schmitz Christian 
Published: January 2022

AbstractThe use of marketing and sales control mechanisms is a core management activity for multinational corporations. However, research on controlling marketing and sales of international subsidiaries is scarce. In particular, the influence of a firm’s economic and cultural environment on different control mechanisms has not been thoroughly examined yet. In attempting to fill these gaps, we build on Jaworski’s (J Mark 52:23–39, 1988) framework from a subsidiary perspective on marketing and sales controls, applied by the headquarters of medium-sized industrial goods corporations. Through a rival model analysis, we determine the impact of the local environmental context on marketing and sales control types exerted by headquarters on subsidiaries located in foreign countries. To analyze the proposed model, this study deploys survey data of 184 subsidiaries from different industries and different European countries with headquarters in Switzerland. The results show that while environmental factors influence the marketing and sales control configurations, the effectiveness of marketing and sales controls is not contingent on environmental factors.
Risk Aversion and Timber Harvest Strategies: A Case Study of Nonindustrial Private Forest Management in Louisiana
Authors: Wang Hua , Adusumilli Naveen , Blazier Michael , Pathak Santosh 
Published: January 2022

AbstractForest owners face many challenges regarding forest management due to the long period from planting to harvest. Along with the economic and environmental factors that influence management actions, the owners' attitude to risk plays a crucial role in forest management decisions. This study shows that understanding the effects of the owner's risk preference for management actions is an important step to form an effective forest policy. The objectives of the study are to (1) assess the economic advantage of forest management alternatives over a range of risk aversion coefficients and (2) determine the financial incentive (risk premium) corresponding to a forest owners' risk attitude. We implemented the stochastic efficiency with respect to a function framework to evaluate a set of fertilization, herbicide, and thinning management alternatives at mid-rotation loblolly pine plantations in Louisiana. Results from this study indicate that forest owner's risk preference affects their decision to select management actions. Financial incentives are substantially different for specific management alternatives between risk-neutral and risk-averse forest owners. The results can guide forest policy development where agencies can modify financial assistance programs to improve the adoption of management actions.
The Mechanism of Stem Cell Aging
Authors: Mi Liangyu , Hu Junping , Li Na , Gao Jinfang , Huo Rongxiu , Peng Xinyue , Zhang Na , Liu Ying , Zhao Hanxi , Liu Ruiling , Zhang Liyun , Xu Ke 
Published: January 2022

AbstractStem cells have self-renewal ability and multi-directional differentiation potential. They have tissue repair capabilities and are essential for maintaining the tissue homeostasis. The depletion of stem cells is closely related to the occurrence of body aging and aging-related diseases. Therefore, revealing the molecular mechanisms of stem cell aging will set new directions for the therapeutic application of stem cells, the study of aging mechanisms, and the prevention and treatment of aging-related diseases. This review comprehensively describes the molecular mechanisms related to stem cell aging and provides the basis for further investigations aimed at developing new anti-stem cell aging strategies and promoting the clinical application of stem cells.
Base Editing of Human Pluripotent Stem Cells for Modeling Long QT Syndrome
Authors: Wu Fujian , Guo Tianwei , Sun Lixiang , Li Furong , Yang Xiaofei 
Published: January 2022

AbstractHuman pluripotent stem cells (hPSCs) have great potential for disease modeling, drug discovery, and regenerative medicine as they can differentiate into many different functional cell types via directed differentiation. However, the application of disease modeling is limited due to a time-consuming and labor-intensive process of introducing known pathogenic mutations into hPSCs. Base editing is a newly developed technology that enables the facile introduction of point mutations into specific loci within the genome of living cells without unwanted genome injured. We describe an optimized stepwise protocol to introduce disease-specific mutations of long QT syndrome (LQTs) into hPSCs. We highlight technical issues, especially those associated with introducing a point mutation to obtain isogenic hPSCs without inserting any resistance cassette and reproducible cardiomyocyte differentiation. Based on the protocol, we succeeded in getting hPSCs carrying LQTs pathogenic mutation with excellent efficiency (31.7% of heterozygous clones, 9.1% of homozygous clones) in less than 20 days. In addition, we also provide protocols to analyze electrophysiological of hPSC-derived cardiomyocytes using multi-electrode arrays. This protocol is also applicable to introduce other disease-specific mutations into hPSCs.
Graphical abstract
A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper
Authors: Zozaya N. , Villaseca J. , Abdalla F. , Calleja M. A. , Díez-Martín J. L. , Estévez J. , García-Sanz R. , Martínez-López J. , Sierra J. , Vera R. , Hidalgo-Vega A. 
Published: January 2022

AbstractCAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.
Letter visual similarity of Japanese hiragana and katakana based on reaction times
Authors: Higuchi Hiroki , Kobayashi Tessei 
Published: January 2022

Abstrac﻿tLetter similarity (i.e., perceptual distance) is a critical measure to better understand letter perception and literacy development. Despite its importance, however, measurements of letter similarity for non-alphabetic scripts are limited, and the shortage of letter similarity for non-alphabetic script interferes with the identification of the universality and the uniqueness of letter perception systems across different scripts. In the present study, we provide a comprehensive matrix of letter similarity for Japanese kana letters (hiragana and katakana). We obtained the discrimination reaction times for simultaneously presented letter pairs and calculated the perceptual distance of 4,278 letter pairs by inversing the time. The matrix showed significant correlations with previously obtained letter similarity for hiragana and katakana. An additional experiment showed that letter pairs for the same sounds (え–エ) produced significantly slower responses compared with those for different sounds (え–コ). However, the differences in reaction times between the same and different sound conditions were smaller than the sequentially presented conditions, suggesting that the matrix was partially attributable to knowledge-based factors (e.g., letter-sound knowledge). This first comprehensive matrix of letter similarity (i.e., perceptual distance) for Japanese kana letters (hiragana and katakana) will be useful for researchers interested in letter perception and literacy development.
Omnichannel Business
Authors: Lehrer Christiane , Trenz Manuel 
Published: January 2022

AbstractThe widespread diffusion of digital technologies along with evolving consumer behaviors and requirements have fostered the emergence of omnichannel businesses, i.e., firms that can exploit integrated processes and information systems to realize a seamless and consistent consumer experience across a plenitude of digital and physical channels. To date, omnichannel research has been cluttered and characterized by significant terminological ambiguity that creates unnecessary challenges for researchers and markeeters trying to navigate and advance research and practice in this area. This fundamentals article seeks to address this problem by presenting a definition of omnichannel business that is grounded in its unique characteristics involving technology, organizational, and market perspectives and clearly distinguishes omnichannel from other terms, such as multi-channel or cross-channel. We leverage this conceptual clarity to analyze and structure the previous research on omnichannel business and conclude with an integrated framework that signifies fields of interest for future omnichannel business research.
Integrated approach to functional analysis of an ERBB2 variant of unknown significance detected by a cancer gene panel test
Authors: Harada Yohei , Sato Akemi , Araki Mitsugu , Matsumoto Shigeyuki , Isaka Yuta , Sagae Yukari , Abe Tomonori , Aoyagi Yasuko , Sueoka Eisaburo , Okuno Yasushi , Kimura Shinya , Sueoka-Aragane Naoko 
Published: January 2022

Abstract
Purpose
Dealing with variants of unknown significance (VUS) is an important issue in the clinical application of NGS-based cancer gene panel tests. We detected a novel ERBB2 extracellular domain VUS, c.1157A > G p.(E401G), in a cancer gene panel test. Since the mechanisms of activation by ERBB2 extracellular domain (ECD) variants are not fully understood, we aimed to clarify those mechanisms and the biological functions of ERBB2 E401G.

Methods
ERBB2 E401G was selected as VUS for analysis because multiple software tools predicted its pathogenicity. We prepared ERBB2 expression vectors with the E401G variant as well as vectors with S310F and E321G, which are known to be activating mutations. On the basis of wild-type ERBB2 or mutant ERBB2 expression in cell lines without ERBB2 amplification or variants, we evaluated the phosphorylation of human epidermal growth factor receptor 2 and related proteins, and investigated with molecular dynamics (MD) simulation the mechanisms conferred by the variants. The biological effects of ERBB2 E401G were also investigated, both in vitro and in vivo.

Results
We found that ERBB2 E401G enhances C-terminal phosphorylation in a way similar to S310F. MD simulation analysis revealed that these variants maintain the stability of the EGFR-HER2 heterodimer in a ligand-independent manner. Moreover, ERBB2 E401G-transduced cells showed an increased invasive capacity in vitro and an increased tumor growth capacity in vivo.

Conclusion
Our results provide important information on the activating mechanisms of ERBB2 extracellular domain (ECD) variants and illustrate a model workflow integrating wet and dry bench processes for the analysis of VUS detected with cancer gene panel tests.
The Patterns of Democracy in Context of Historical Political Science
Authors: He Jiacheng 
Published: January 2022

AbstractThe patterns of democracy are related to the success or failure of national governance; hence, they are a key topic in the theoretical research of political science. It is difficult to comprehend the worldwide political conflicts caused by the promotion of liberal democracy in the study of democratic models that have liberal democracy as their core. The emphasis of historical political science on the genes of civilization provides an opportunity to reinterpret the patterns of democracy. Relying on specific civilization genes, the patterns of democracy can be divided into the “value pattern”, which is shaped by historical civilization genes, and the “practice pattern”, which is based on the “value pattern”. Based on Christian concepts, Western civilization produced liberal democracy as the value pattern, and the value is inherited through the practice pattern of party democracy. Chinese civilization has continued the tradition of people-orientation and consultative practice, establishing socialist democracy in value and consultative democracy in practice. Theoretically, the analytical framework of the value pattern and the practice pattern of democracy illustrates the source of the diverse patterns of democracy, which helps demonstrate the limitations of liberal democracy and points out the possibility of developing a non-liberal democracy pattern.
On the difference of inverse coefficients of convex functions
Authors: Sim Young Jae , Thomas Derek K. 
Published: January 2022

AbstractLet f be analytic in the unit disk $${\mathbb {D}}=\{z\in {\mathbb {C}}:|z|<1 \}$$

D
=
{
z
∈
C
:
|
z
|
<
1
}

, and $${\mathcal {S}}$$
S
be the subclass of normalised univalent functions given by $$f(z)=z+\sum _{n=2}^{\infty }a_n z^n$$

f

(
z
)

=
z
+

∑

n
=
2

∞

a
n

z
n

for $$z\in {\mathbb {D}}$$

z
∈
D

. Let F be the inverse function of f defined in some set $$|\omega |\le r_{0}(f)$$

|
ω
|

≤

r
0

(
f
)

, and be given by $$F(\omega )=\omega +\sum _{n=2}^{\infty }A_n \omega ^n$$

F

(
ω
)

=
ω
+

∑

n
=
2

∞

A
n

ω
n

. We prove the sharp inequalities $$-1/3 \le |A_4|-|A_3| \le 1/4$$

-
1
/
3
≤
|

A
4

|
-
|

A
3

|
≤
1
/
4

for the class $${\mathcal {K}}\subset {\mathcal {S}}$$

K
⊂
S

of convex functions, thus providing an analogue to the known sharp inequalities $$-1/3 \le |a_4|-|a_3| \le 1/4$$

-
1
/
3
≤
|

a
4

|
-
|

a
3

|
≤
1
/
4

, and giving another example of an invariance property amongst coefficient functionals of convex functions.
Fibro-adipogenesis in Injured Rotator Cuff Muscle
Authors: Subhash Ajith K. , Davies Michael , Gatto Andrew , Bogdanov Jacob M. , Lan Rae , Jensen Andrew , Feeley Brian T. , Petrigliano Frank A. 
Published: January 2022

Abstract
Purpose of Review
Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue.

Recent Findings
Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression.

Summary
The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.