bluuebunny/crossref_metadata_2025_split huggingface dataset:
A237 IMPROVEMENT IN ABDOMINAL SYMPTOMS WITH LINACLOTIDE IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION: RESULTS FROM A PHASE 3B TRIAL
Authors: Sidani S , Boutros K , Sayuk G S , Gonzalez H , Brenner D M 
Published: March 2021

Abstract

Background
Linaclotide (LIN) is a guanylate cyclase-C agonist approved to treat irritable bowel syndrome with constipation (IBS-C) in adults. Abdominal symptoms are important to patients with IBS-C. In a recent Phase 3b study, LIN significantly improved a composite score of abdominal bloating, pain, and discomfort (Abdominal Score), which was used as the primary endpoint in the study.

Aims
To evaluate the efficacy of LIN for improving additional efficacy abdominal symptom endpoints in a randomized, double-blind, placebo (PBO)-controlled Phase 3 study of LIN in patients with IBS-C.

Methods
Adults with IBS-C were randomized to PBO (N=308) or LIN 290 μg (N=306) once daily for 12 weeks. Patients recorded their daily abdominal symptoms, including the individual items of bloating, pain, and discomfort, using an 11-point scale (0–10; 0=none, 10=worst possible). The primary endpoint was the Abdominal Score. Additional efficacy endpoints included 6/12-week abdominal pain and constipation (APC)+1 responder, 6/12-week abdominal bloating responder, 6/12-week abdominal pain responder, and 6/12-week abdominal discomfort responder. For individual symptoms, a responder was a patient who had an improvement from baseline of ≥2 points in the respective endpoint for ≥6 of the 12 weeks. Changes from baseline (CFB) over 12 weeks in abdominal bloating, pain, and discomfort were evaluated using a mixed model with repeated measures framework. Proportions of responders were compared between groups for each responder endpoint using a Cochran-Mantel-Haenszel test.

Results
614 patients (mean age, 46.7 years; 81% female; similar baseline abdominal symptoms) were randomized. LIN-treated patients had greater least-squares mean (LSM) CFB in abdominal bloating (LSM difference [95% CI]: –0.889 [–1.249, –0.530], p&lt;0.001), pain (–0.881 [–1.238, –0.524], p&lt;0.001), and discomfort (–0.837 [–1.196, –0.478], p&lt;0.001) compared to PBO-treated patients. There was a greater proportion of LIN-treated vs. PBO-treated patients who were 6/12-week APC+1 (29% vs. 17%; p=0.0003), bloating (40% vs. 24%; p&lt;0.001), pain (42% vs. 25%; p&lt;0.001), and discomfort (42% vs. 26%; p&lt;0.001) responders (Figure). Diarrhea was the most common treatment-emergent adverse event (LIN: 4.6%; PBO: 1.6%).

Conclusions
LIN significantly improved multiple abdominal symptom and secondary responder endpoints in patients with IBS-C. These results support the effectiveness of LIN for improving a spectrum of abdominal symptoms in IBS-C.

Funding Agencies
This study was sponsored by Allergan plc, Dublin, Ireland (prior to acquisition by AbbVie Inc.). Writing and editorial assistance were provided to the authors by Brittany Y. Jarrett, PhD, Jane Beck, MA, and Rebecca Fletcher, BA(Hons) of Complete HealthVizion, Inc., Chicago, IL, USA and funded by Allergan plc (prior to acquisition by AbbVie Inc.).
Accidental digital epinephrine injection injury: a case of conservative management
Authors: Mortada Hatan , Ahmed Bandari Abdullah , Arab Khalid 
Published: March 2021

Abstract
The open access to epinephrine autoinjectors has resulted in an increased number of reports related to accidental injection into the digits. The appropriate management after accidental injection remains controversial. This study presents the first case in Saudi Arabia of a young man who accidentally injected epinephrine into the thumb and a literature review of the treatment options available. A 19-year-old man presented with accidental injection of 300 mcg of epinephrine into the volar pulp of his right thumb while treating an allergic reaction. The embedded needle was removed by countertraction and irrigation. The examination results were normal. The patient was discharged with prophylactic antibiotic and analgesia. Later, the puncture wound healed and vascularity and sensation remained intact. Conservative management and observation are advantageous in certain cases if vascular function is uncompromised. This case highlights the importance of education about the correct handling and administration of the epinephrine injection.
SARS-CoV-2 in peritoneal swabs from asymptomatic patients undergoing emergency abdominal surgery
Authors: AlAradi Jasim , AlHarmi Rawan A Rahman , AlKooheji Mariam , Almahari Sayed Ali , Isa Mohamed Abdulla , AlMarzooq Raed 
Published: March 2021

Abstract
This is a case series of five patients with acute abdomen requiring surgery who tested positive for coronavirus disease 2019 (COVID-19) and were asymptomatic, with the purpose of detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in peritoneal fluid. Nasopharyngeal swab was done as a prerequisite for admission or prior to admission as part of random testing. Two methods of viral testing were employed: Xpert® Xpress SARS-CoV-2 (rapid test) and real-time reverse transcription polymerase chain reaction (RT-PCR). Either or both tests were done, with the former performed for patients requiring surgery immediately. Surgery was performed within 24–36 h from admission. Peritoneal fluid swabs were obtained for the detection of SARS-CoV-2 using RT-PCR test. Swabs were immediately placed in viral transfer media and delivered to the public health laboratory in an ice bag. SARS-CoV-2 was not detected in peritoneal swabs. Due to the limited number of patients, further studies are required; yet, protective measures should still be taken by surgeons when dealing with COVID-19 cases.
The use of percutaneous-endoscopic rendezvous stenting in a patient with bile duct injury after cholecystectomy—and a unique complication requiring secondary endoscopic intervention
Authors: Vidovszky Anna A , Qafiti Fred , El Haddi S James , Doukides Theodore , Hus Nir , Genuit Thomas 
Published: March 2021

Abstract
Bile duct injury (BDI) is a potentially devastating complication after cholecystectomy. Familiarity with the diagnosis and multidisciplinary treatment options is imperative. This report highlights the utility of the rendezvous stenting procedure in a high-risk patient and describes a rare complication involving stent misplacement through the surgical drain. This is a 96-year-old female patient who suffered a Strasburg Class D injury during cholecystectomy, repaired over a T-tube. The T-tube dislodged postoperatively. Endoscopic and transhepatic stenting attempts were unsuccessful. Ultimately, a rendezvous approach allowed successful deployment of a covered metal stent. The stent was inadvertently deployed through a side fenestration of a surgical drain and was explanted upon drain removal. Repeat endoscopic stent placement was successful. The patient recovered without further complication. Surgical drains near the BDI can become sources of unexpected complications. A higher index of suspicion and careful interpretation of procedural imaging studies may prevent this complication.
Beyond the hubble sequence – exploring galaxy morphology with unsupervised machine learning
Authors: Cheng Ting-Yun , Huertas-Company Marc , Conselice Christopher J , Aragón-Salamanca Alfonso , Robertson Brant E , Ramachandra Nesar 
Published: March 2021

ABSTRACT
We explore unsupervised machine learning for galaxy morphology analyses using a combination of feature extraction with a vector-quantized variational autoencoder (VQ-VAE) and hierarchical clustering (HC). We propose a new methodology that includes: (1) consideration of the clustering performance simultaneously when learning features from images; (2) allowing for various distance thresholds within the HC algorithm; (3) using the galaxy orientation to determine the number of clusters. This set-up provides 27 clusters created with this unsupervised learning that we show are well separated based on galaxy shape and structure (e.g. Sérsic index, concentration, asymmetry, Gini coefficient). These resulting clusters also correlate well with physical properties such as the colour–magnitude diagram, and span the range of scaling relations such as mass versus size amongst the different machine-defined clusters. When we merge these multiple clusters into two large preliminary clusters to provide a binary classification, an accuracy of $\sim 87{{\ \rm per\ cent}}$ is reached using an imbalanced data set, matching real galaxy distributions, which includes 22.7 per cent early-type galaxies and 77.3 per cent late-type galaxies. Comparing the given clusters with classic Hubble types (ellipticals, lenticulars, early spirals, late spirals, and irregulars), we show that there is an intrinsic vagueness in visual classification systems, in particular galaxies with transitional features such as lenticulars and early spirals. Based on this, the main result in this work is not how well our unsupervised method matches visual classifications and physical properties, but that the method provides an independent classification that may be more physically meaningful than any visually based ones.
A 2-d orbital period for a redback millisecond pulsar candidate in the globular cluster NGC 6397
Authors: Marcano Manuel Pichardo , Rivera Sandoval Liliana E , Maccarone Thomas J , Zhao Yue , Heinke Craig O 
Published: March 2021

ABSTRACT
We report optical modulation of the companion to the X-ray source U18 in the globular cluster NGC 6397. U18, with combined evidence from radio and X-ray measurements, is a strong candidate as the second redback in this cluster, initially missed in pulsar searches. This object is a bright variable star with an anomalous red colour and optical variability (∼0.2 mag in amplitude) with a periodicity ∼1.96 d that can be interpreted as the orbital period. This value corresponds to the longest orbital period for known redback candidates and confirmed systems in Galactic globular clusters and one of the few with a period longer than 1 d.
A Conceptual Model for Individual Coping with Value Conflicts
Authors: Jaspers Sylke 
Published: March 2021

AbstractConflicting values that are sometimes impossible to resolve are one of the costs of public governance for public values and public outcomes. To unravel one of the mechanisms enhancing or obstructing public values or public outcomes in public governance, this article presents the individual coping with value conflicts model. The model focuses on individually experienced value conflicts regarding public values realization (i.e., the principles of governance) and public value creation (i.e., public outcomes) necessitating coping strategies. The article discusses various aspects of the theoretical model. The various coping strategies and their likely results are connected to public values realization and public value creation. However, first, the article identifies the origins of the need to rely on coping strategies, such as value pluralism and plural expectations of individuals. Next, the paper hypothesizes that individual coping strategies are driven by the psychological traits of individuals and influenced by interactions. The article further explains that the individual’s role in adopting coping strategies manifests in specific situations or contexts. The paper concludes with implications for public value(s) theories, makes suggestions for applications of the model, and sets out avenues for empirical research to test and advance the model.
Record-Keeping and Cooperation in Large Societies
Authors: Clark Daniel , Fudenberg Drew , Wolitzky Alexander 
Published: March 2021

Abstract
We introduce a new model of repeated games in large populations with random matching, overlapping generations, and limited records of past play. We prove that steady-state equilibria exist under general conditions on records. When the updating of a player’s record can depend on the actions of both players in a match, any strictly individually rational action can be supported in a steady-state equilibrium. When record updates can depend only on a player’s own actions, fewer actions can be supported. Here, we focus on the prisoner’s dilemma and restrict attention to strict equilibria that are coordination-proof, meaning that matched partners never play a Pareto-dominated Nash equilibrium in the one-shot game induced by their records and expected continuation payoffs. Such equilibria can support full cooperation if the stage game is either “strictly supermodular and mild” or “strongly supermodular,” and otherwise permit no cooperation at all. The presence of “supercooperator” records, where a player cooperates against any opponent, is crucial for supporting any cooperation when the stage game is “severe.”
Overcoming vested interests against innovation through political entrepreneurship: A comparative study of Korean mobility cases
Authors: Choi Yong In , Kim Byoung-Joo 
Published: March 2021

AbstractTechnological innovators encounter resistance when vested interests organize collective actions to block progress and preserve their turfs. Some innovators make politically strategic and tactical choices to overcome such resistance, while others take different paths and fail. To identify factors enabling the successful management of resistance, this study reviews relevant theoretical concepts, examines and compares two recent Korean mobility cases, and discusses their policy implications. ‘Political entrepreneurship’ of innovators plays a critical role in enabling innovative newcomers overcome collective action by vested interests. Successful political entrepreneurship seeks compromises and win-win solutions. This paper adds to science, technology, and innovation literature by suggesting that policymakers should do what they can to encourage innovative newcomers to pursue ‘political entrepreneurship’ when they face seemingly insurmountable opposition. This study builds on Mancur Olson’s theory of collective action in the context of innovations studies, by adding ‘political entrepreneurship’ and broadening the scope for resolving the Olsonian dilemma.
Rationale, protocol and baseline characteristics of the metabolome, microbiome, and dietary salt intervention study (MetaSalt)
Authors: Ruan Zengliang , Li Jianxin , Liu Fangchao , Cao Jie , Chen Shufeng , Chen Jichun , Huang Keyong , Wang Yaqin , Li Hongfan , Wang Yan , Zhongyu Xue , Wang Laiyuan , Huang Jianfeng , Gu Dongfeng , Lu Xiangfeng 
Published: March 2021

AbstractHigh sodium intake has been recognized as an important risk factor for hypertension, but the role of gut microbiota composition and metabolomic profiles in the association between dietary sodium intake and blood pressure (BP) is uncertain. The metabolome, microbiome, and dietary salt intervention study (MetaSalt) study was conducted to investigate whether low- and high-dietary sodium intake influences BP by changing the microbial and metabolomic profiles. This is a family-based, multicentre intervention study conducted in four rural field-centres across three provinces in rural Northern China. Probands with untreated prehypertension or stage-1 hypertension were identified through a community-based BP screening, and their family members included siblings, offspring, spouses and parents were subsequently included. During the dietary intervention, low-salt and high-salt diets were provided free of charge to all participants. A total of 529 participants in four field centres were included in our study, with a mean age of 48.1 years old, and about 36.7% of them were male, 76.5% had a middle school (69.5%) or higher (7.0%) diploma, 23.4% had a history of smoke, 24.4% were current drinkers. The mean systolic and diastolic BP levels in the baseline were 129.54 mm Hg and 81.02 mm Hg for all participants, and significantly decreased during the low-salt intervention and increased during the high-salt intervention. Our study is well placed to check the impacts of dietary sodium intake on microbial and metabolomic profiles, which will have important implications for discovering the mechanisms in the development of hypertension and subsequent cardiovascular disease.
The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies and targets both the NTD and the RBD
Authors: Amanat Fatima , Thapa Mahima , Lei Tinting , Sayed Ahmed Shaza M. , Adelsberg Daniel C. , Carreno Juan Manuel , Strohmeier Shirin , Schmitz Aaron J. , Zafar Sarah , Zhou Julian Q , Rijnink Willemijn , Alshammary Hala , Borcherding Nicholas , Reiche Ana Gonzalez , Srivastava Komal , Sordillo Emilia Mia , van Bakel Harm ,   The Personalized Virology Initiative, Turner Jackson S. , Bajic Goran , Simon Viviana , Ellebedy Ali H. , Krammer Florian 
Published: March 2021

SummaryIn this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.
Capsaicin activates TRPV1 in human Langerhans cells and inhibits mucosal HIV-1 transmission via secreted CGRP
Authors: Cohen Emmanuel , Zhu Aiwei , Auffray Cédric , Bomsel Morgane , Ganor Yonatan 
Published: March 2021

AbstractUpon its mucosal transmission, human immunodeficiency virus type 1 (HIV-1) rapidly targets resident antigen-presenting Langerhans cells (LCs) in genital epithelia, which subsequently trans-infect CD4+ T-cells. We previously described an inhibitory neuro-immune sensory mucosal crosstalk, whereby peripheral pain-sensing nociceptor neurons, innervating all mucosal epithelia and associating with LCs, secret the neuropeptide calcitonin gene-related peptide (CGRP) that strongly inhibits HIV-1 trans-infection. Moreover, we reported that LCs secret low levels of CGRP that are further increased by CGRP itself via an autocrine/paracrine mechanism. As nociceptors secret CGRP following activation of their Ca2+ion channel transient receptor potential vanilloid 1 (TRPV1), we investigated whether LCs also express functional TRPV1. We found that human LCs expressed TRPV1 mRNA and protein. TRPV1 in LCs was functional, as the TRPV1 agonists capsaicin (CP) and resiniferatoxin (RTX) induced Ca2+influx in a dose-dependent manner. Treatment of LCs with CP and the TRPV1 agonist rutaecarpine (Rut) increased CGRP secretion, reaching concentrations close to its IC50for inhibition of HIV-1 trans-infection. Accordingly, CP significantly inhibited HIV-1 trans-infection, which was abrogated by antagonists of both TRPV1 and the CGRP receptor. Finally, pre-treatment of inner foreskin tissue explants with CP markedly increased CGRP secretion, and upon subsequent polarized exposure to HIV-1, inhibited increase in LC-T-cell conjugate formation and T-cell infection. Together, our results reveal that alike nociceptors, LCs express functional TRPV1, whose activation induces CGRP secretion that inhibits mucosal HIV-1 transmission. Our studies could permit re-positioning of formulations containing TRPV1 agonists, already approved for pain relief, as novel topical microbicides against HIV-1.Significance StatementUpon its sexual transmission, HIV-1 targets different types of mucosal immune cells, such as antigen-presenting Langerhans cells (LCs). In turn, LCs transfer HIV-1 to its principal cellular targets, namely CD4+ T-cells, in a process termed trans-infection. We previously discovered that the mucosal neuropeptide CGRP strongly inhibits trans-infection. CGRP is principally secreted from pain-sensing peripheral neurons termed nociceptors, once activated via their TRPV1 ion channel. Herein, we reveal that LCs also express functional TRPV1, whose activation induces secretion of CGRP that inhibits mucosal HIV-1 transmission. Accordingly, molecules activating TRPV1 and inducing CGRP secretion could be used to prevent mucosal HIV-1 transmission. This approach represents an original neuro-immune strategy to fight HIV-1.
Molecular and Structural Basis of Olfactory Sensory Neuron Coalescence by Kirrel Receptors
Authors: Wang Jing , Vaddadi Neelima , Pak Joseph S. , Park Yeonwoo , Quilez Sabrina , Roman Christina A. , Dumontier Emilie , Thornton Joseph W. , Cloutier Jean-François , Özkan Engin 
Published: March 2021

ABSTRACTProjections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal IG domains is necessary and sufficient to create homodimers, and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3in vivoleads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed inKirrel3-/-animals. Our results provide strong evidence for Kirrel3 homodimerization controlling axonal coalescence.
Crystal structure refinements of stoichiometric Ni3Se2 and NiSe
Authors: Unoki Kohei , Yoshiasa Akira , Kitahara Ginga , Nishiayama Tadao , Tokuda Makoto , Sugiyama Kazumasa , Nakatsuka Akihiko 
Published: March 2021

Single crystals of Ni3Se2 (trinickel diselenide) and NiSe (nickel selenide) with stoichiometric chemical compositions were grown in evacuated silica-glass tubes. The chemical compositions of the single crystals of Ni3Se2 and NiSe were determined by scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM/EDS). The crystal structures of Ni3Se2 [rhombohedral, space group R32, a = 6.02813 (13), c = 7.24883 (16) Å, Z = 3] and NiSe [hexagonal, space group P63/mmc, a = 3.66147 (10), c = 5.35766 (16) Å, Z = 2] were analyzed by single-crystal X-ray diffraction and refined to yield R values of 0.020 and 0.018 for 117 and 85 unique reflections, respectively, with F
o > 4σ(F
o). R32 is a Sohncke type of space group where enantiomeric structures can exist; the single-domain structure obtained by the refinement was confirmed to be correct by a Flack parameter of −0.05 (2). The existence of Ni—Ni bonds was confirmed in both compounds, in addition to the Ni—Se bonds. The value of the atomic displacement parameter (mean-square displacement) of each atom in NiSe was larger than that in Ni3Se2. The larger amplitude of the atoms in NiSe corresponds to longer Ni—Se and Ni—Ni bond lengths in NiSe than in Ni3Se2. The Debye temperatures, θD, estimated from observed mean-square displacements for Ni and Se in Ni3Se2, were 322 and 298 K, respectively, while those for Ni and Se in NiSe were 246 and 241 K, respectively. The existence of large cavities in the structure and the weak bonding force are likely responsible for the brittle and soft nature of the NiSe crystal.