bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and pharmacokinetics of BI 685509, a soluble guanylyl cyclase activator, in patients with cirrhosis: A randomized Phase Ib study
Authors: Lawitz Eric J. , Reiberger Thomas , Schattenberg Jörn M. , Schoelch Corinna , Coxson Harvey O. , Wong Diane , Ertle Judith 
Published: October 2023

Background:
Portal hypertension is a severe complication of cirrhosis. This Phase Ib study (NCT03842761) assessed the safety, tolerability, and pharmacokinetics of soluble guanylyl cyclase activator BI 685509 in patients with mild or moderate hepatic impairment (Child–Pugh [CP] A or B cirrhosis) and healthy volunteers (HVs).

Methods:
In this single-center, randomized, placebo-controlled study, patients received BI 685509 (maximum doses: 1, 2, or 3 mg, twice daily [BID]) or placebo for 28 days. HVs received one 0.5 mg dose of BI 685509 or placebo.

Results:
In total, 64 participants (CP-A, n=24; CP-B, n=25; HVs, n=15) were included; most commonly with NAFLD (36.7%), alcohol-associated (30.6%), or chronic viral hepatitis-related cirrhosis (28.6%). In patients with CP-A cirrhosis, drug-related adverse events (AEs) occurred in 5.6% of BI 685509-treated patients and 16.7% of placebo recipients. In patients with CP-B cirrhosis, drug-related AEs occurred in 26.3% of BI 685509-treated patients only. No serious AEs occurred in patients with CP-A cirrhosis; in patients with CP-B cirrhosis, serious AEs (not drug-related) occurred in 10.5% of BI 685509-treated patients and 16.7% of patients receiving placebo. BI 685509 was rapidly absorbed; exposure increased with dosage and was similar between etiologies and between patients with CP-A cirrhosis and patients with CP-A cirrhosis but lower in HVs. The mean percentage portal–systemic shunt fraction was measured in patients with CP-A cirrhosis and decreased at the end of treatment in the 2 mg BID (–11.2 ± 11.9%) and 3 mg BID (–14.0 ± 8.4%) BI 685509 dose groups, but not in the placebo group (+1.0 ± 27.3%).

Conclusion:
BI 685509 was generally well tolerated, with 3 serious, not drug-related AEs reported in patients with CP-B cirrhosis. In patients with CP-A cirrhosis, portal–systemic shunt fraction in the exploratory efficacy analysis was reduced by 2 mg BID and 3 mg BID BI 685509.
Inactivation of the paraventricular nucleus attenuates the cardiogenic sympathetic afferent reflex in the spontaneously hypertensive rat
Authors: Zahner Matthew R. , Brown Mary C. , Chandley Michelle J. 
Published: October 2023

Background:
Myocardial ischemia causes the release of bradykinin, which stimulates cardiac afferents, causing sympathetic excitation and chest pain. Glutamatergic activation of the paraventricular hypothalamic nucleus (PVN) in the spontaneously hypertensive rat (SHR) drives elevated basal sympathetic activity. Thus, we tested the hypothesis that inactivation of the PVN attenuates the elevated reflex response to epicardial bradykinin in the SHR and that ionotropic PVN glutamate receptors mediate the elevated reflex.

Methods:
We recorded the arterial pressure and renal sympathetic nerve activity (RSNA) response to epicardial bradykinin application in anesthetized SHR and Wistar Kyoto (WKY) rats before and after PVN microinjection of GABAA agonist muscimol or ionotropic glutamate receptor antagonist kynurenic acid.

Results:
Muscimol significantly decreased the arterial pressure response to bradykinin from 180.4 ± 5.8 to 119.5 ± 6.9 mmHg in the SHR and from 111.8 ± 7.0 to 84.2 ± 8.3 mmHg in the WKY and the RSNA response from 186.2 ± 7.1 to 142.7 ± 7.3% of baseline in the SHR and from 201.0 ± 11.5 to 160.2 ± 9.3% of baseline in the WKY. Kynurenic acid significantly decreased the arterial pressure response in the SHR from 164.5 ± 5.0 to 126.2 ± 7.7 mmHg and the RSNA response from 189.9 ± 13.7to 168.5 ± 12.7% of baseline but had no effect in the WKY.

Conclusion:
These results suggest that tonic PVN activity is critical for the full manifestation of the CSAR in both the WKY and SHR. Glutamatergic PVN activity contributes to the augmented CSAR observed in the SHR.
Orthostatic hypotension, orthostatic hypertension, and ambulatory blood pressure in patients with chronic kidney disease in CRIC
Authors: Ghazi Lama , Cohen Jordana B. , Townsend Raymond R. , Drawz Paul E. , Rahman Mahboob , Pradhan Nishigandha , Cohen Debbie L. , Weir Matthew R. , Rincon-Choles Hernan , Juraschek Stephen P. 
Published: October 2023

Background:
Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown.

Methods:
CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP.

Results:
Of the 1386 participants (age: 58 ± 10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (β = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (β = -4 [-7.2, -0.5]) and diastolic WCE (β = -6 [-8.1, -4.2]).

Conclusion:
Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes.
Visual outcomes and risk factors of uveitis cataract eyes after phacoemulsification and manual small-incision cataract surgery
Authors: Shekhar Madhu , Chaudhary Sushmita , Pai Aruna , Rajesh Vedhanayaki , Balakrishnan Logesh , Nagu Kamatchi , Wijesinghe Hiruni Kaushalya 
Published: October 2023

Purpose:
To examine the visual outcomes and risk factors of uveitis cataract eyes after phacoemulsification and manual small-incision cataract surgery (MSICS).

Setting:
Tertiary-care eye hospital in southern India.

Design:
Retrospective interventional case series.

Methods:
Of the uveitis eyes operated for cataract surgery between 2017 and 2020, eyes with a minimum of 6 months postoperative follow-up were included. Eyes with ocular trauma, lens subluxation, lens-induced uveitis, or retinal detachment–induced uveitis were excluded. Demography, visual acuity, intraoperative and postoperative records, and surgical outcomes were analyzed.

Results:
191 eyes of 191 patients with a mean age of 51.7 ± 14.4 years were included. Phacoemulsification was performed in 134 eyes, and 57 eyes underwent MSICS. Synechiolysis and pupil-expanding maneuvers were required in 74 eyes (38.7%). No differences were noted in the rates of complications between phacoemulsification and MSICS eyes, except at 1 year, where higher rates of posterior capsular opacification and vitritis were noted in MSICS eyes (P = .018). The visual outcomes of eyes that underwent MSICS and phacoemulsification were comparable (P = .463). In 12 eyes (13.5%), improvement in vision was not significant.

Conclusions:
This study shows phacoemulsification may be a preferred technique in uveitis cataracts, given the lesser incidence of postoperative complications. Patients should be counseled for realistic expectations.
The effect of experimental emotion induction on experimental pain: a systematic review and meta-analysis
Authors: Mikkelsen Mai Bjørnskov , Neumann Henrike , Buskbjerg Cecilie Rask , Johannsen Maja , O'Toole Mia Skytte , Arendt-Nielsen Lars , Zachariae Robert 
Published: October 2023

Abstract
The idea that emotions can influence pain is generally recognized. However, a synthesis of the numerous individual experimental studies on this subject is lacking. The aim of the present systematic review and meta-analysis was to synthesize the existing evidence on the effect of experimental emotion induction on experimental pain in nonclinical adults. PsycInfo and PubMed were searched up until April 10, 2023, for studies assessing differences in self-reported pain between emotion induction groups and/or control groups or between conditions within group. Risk of bias was assessed for the individual studies. The literature search yielded 78 relevant records of 71 independent studies. When compared with control conditions, the pooled results revealed a statistically significant pain-attenuating effect of positive emotion induction (between-group: Hedges g = −0.48, 95% CI: −0.72; −0.25, K = 9; within-group: g = −0.24, 95% CI: −0.32; −0.15, K = 40), and a statistically significant pain-exacerbating effect of negative emotion induction in within-group analyses but not between-group analyses (between-group: g = −0.29, 95% CI: −0.66; 0.07, K = 10; within-group: g = 0.14, 95% CI: 0.06; 0.23, K = 39). Bayesian meta-analysis provided strong support for an effect of positive emotion induction but weak support for an effect of negative emotion induction. Taken together, the findings indicate a pain-attenuating effect of positive emotion induction, while the findings for negative emotion induction are less clear. The findings are discussed with reference to theoretical work emphasizing the role of motivational systems and distraction for pain. Limitations include considerable heterogeneity across studies limiting the generalizability of the findings.
Deactivation of dorsal CA1 pyramidal neurons projecting to medial prefrontal cortex contributes to neuropathic pain and short-term memory impairment
Authors: Han Shuang , Ren Jiale , Li Ziming , Wen Junjian , Jiang Bin , Wei Xuhong 
Published: October 2023

Abstract
Neuropathic pain after peripheral nerve injury is a multidimensional experience that includes sensory, affective, and cognitive components that interact with one another. Hypoexcitation of the medial prefrontal cortex (mPFC) was observed in mice with peripheral nerve injury, but the changes in neural inputs onto the mPFC have not been completely explored. Here, we report that the neural terminals from the dorsal hippocampus CA1 (dCA1) form excitatory connection with layer 5 pyramidal neurons in the prelimbic area (PrL) of the mPFC. Spared nerve injury (SNI) induced a reduction in the intrinsic excitability of dCA1 pyramidal neurons innervating the PrL and impairment in excitatory synaptic transmission onto dCA1 pyramidal cells. Specifically, activating the neural circuit from dCA1 to mPFC alleviated neuropathic pain behaviors and improved novel object recognition ability in SNI mice, whereas deactivating this pathway in naïve animals recapitulated tactile allodynia and memory deficits. These results indicated that hypoactivity in dCA1 pyramidal cells after SNI in turn deactivated layer 5 pyramidal neurons in PrL and ultimately caused pain hypersensitivity and memory deficits.
A Multicenter Comparison of 1-yr Functional Outcomes and Programming Differences Between the Advanced Bionics Mid-Scala and SlimJ Electrode Arrays
Authors: Eitutis Susan T. , Vickers Deborah A. , Tebbutt Karen , Thomas Tisa , Jiang Dan , de Klerk Anel , Clemesha Jennifer , Chung Mark , Bance Manohar L. 
Published: October 2023

ObjectiveTo determine if there is a difference in hearing outcomes or stimulation levels between Advanced Bionics straight and precurved arrays.Study designRetrospective chart review across three implant centers.SettingTertiary centers for cochlear and auditory brainstem implantation.PatientsOne hundred fifteen pediatric and 205 adult cochlear implants (CIs) were reviewed. All patients were implanted under the National Institute for Health and Care Excellence 2009 guidelines with a HiRes Ultra SlimJ or Mid-Scala electrode array.Main outcome measuresHearing preservation after implantation, as well as CI-only listening scores for Bamford-Kowal-Bench sentences were compared 1 year after implantation. Stimulation levels for threshold and comfort levels were also compared 1 year after implantation.ResultsHearing preservation was significantly better with the SlimJ compared with the Mid-Scala electrode array. Bamford-Kowal-Bench outcomes were not significantly different between the two arrays in any listening condition. Stimulation levels were not different between arrays but did vary across electrode contacts. At least one electrode was deactivated in 33% of implants but was more common for the SlimJ device.ConclusionModern straight and precurved arrays from Advanced Bionics did not differ in hearing performance or current requirements. Although hearing preservation was possible with both devices, the SlimJ array would still be the preferred electrode in cases where hearing preservation was a priority. Unfortunately, the SlimJ device was also prone to poor sound perception on basal electrodes. Further investigation is needed to determine if deactivated electrodes are associated with electrode position/migration, and if programming changes are needed to optimize the use of these high-frequency channels.
Navigation systems and 3D imaging in percutaneous nephrolithotripsy: improving outcomes and safety
Authors: Bouchalakis Athanasios , Somani Bhaskar Kumar , Lima Estevao , Rassweiler-Seyfried Marie-Claire , Mamoulakis Charalampos , Tokas Theodoros 
Published: October 2023

Purpose of review
Percutaneous nephrolithotripsy (PCNL) is the first-line management option for large kidney stones (>2 cm). It remains, however, a demanding procedure with considerable morbidity. The present narrative review summarizes recent knowledge from original research studies investigating navigation systems/three-dimensional (3D) imaging in PCNL, particularly on publications during the past 12–18 months.

Recent findings
Navigation systems and 3D imaging are primarily used for preoperative planning, with few intra-operative applications. Patient management and residents’ training could benefit from their use.

Summary
Navigation systems and 3D imaging technology have emerged as a potential game-changer in PCNL. Even though available evidence is currently scarce/inconclusive, the safety/efficacy of navigation systems and 3D dimensional imaging use in PCNL appears promising. This advanced technology offers precise anatomical mapping, improved visualization, and surgical accuracy. Enabling a comprehensive preoperative evaluation and improving guidance, navigation systems, and 3D imaging technology may improve the safety and efficacy of PCNL. With continuous technological evolution, it is expected that improvements/innovations will offer further aid in such demanding procedures. Familiarization and cost reduction are necessary for widespread application, while larger-scale prospective studies and well designed randomized controlled trials are still needed.
Sexual Distancing During 5 Periods Around and During the COVID-19 Pandemic, Amsterdam, the Netherlands
Authors: de Vries Dominique C. , Jongen Vita W. , Zimmermann Hanne M.L. , Davidovich Udi , Hoornenborg Elske , de Vries Henry J.C. 
Published: October 2023

Background
Social and sexual distancing (ie, abstaining from sex with persons outside one's household) was important in the control of the COVID-19 pandemic. Compliance to distancing measures can change over time. We assessed changes in compliance to the sexual distancing measures during five periods of the COVID-19 pandemic in the Netherlands.

Methods
Between November 2021 and March 2022, we used a structured questionnaire containing questions about sexual behavior and factors that could have influenced compliance with sexual distancing. Variables related to sexual behavior were measured for 5 periods, before and during the pandemic, delineated by imposement and relaxation of lockdown measures.

Results
Eight hundred seventy participants (predominantly MSM) completed the questionnaire. We found that compliance to the sexual distancing measures decreased over time. The number of casual partners was highest after the lockdown measures were relaxed for the second time (April 2021 to March 2022), and even higher than before the first lockdown. Factors positively associated with sexual distancing compliance were: having confidence in the information provided by the government and experiencing less or similar need for physical contact compared with before the pandemic. Factors that lowered compliance over time were: previously having had COVID-19, perceiving the lockdown measures as overstated, having sex with casual partners and similar drug use during the pandemic as before.

Conclusions
Our findings suggest that sexual distancing measures are difficult to maintain for a long period. Other measures, such as confinement to a small network of known partners, might be more effective for longer pandemics in minimizing the spread of infectious diseases.
Qualitative Point-of-Care Ultrasound Enema Management for Constipation
Authors: Riera Antonio , Phatak Uma P. 
Published: October 2023

Abstract
We discuss 10 cases where the qualitative evaluation of hard stool in the rectum with point-of-care ultrasound helped guide enema administration in a pediatric emergency department. Point-of-care ultrasound findings were especially valuable in cases where the presenting symptoms were undifferentiated, a language barrier was present, or the guardian and child denied that constipation was an active problem. When sodium phosphate enema administration was done in the pediatric emergency department, evacuation of the rectal stool burden was observed in most cases before final disposition.
Leveraging social networks for identification of people with HIV who are virally unsuppressed
Authors: Cummins Breschine , Johnson Kara , Schneider John A. , Del Vecchio Natascha , Moshiri Niema , Wertheim Joel O. , Goyal Ravi , Skaathun Britt 
Published: October 2023

Objectives:
This study investigates primary peer-referral engagement (PRE) strategies to assess which strategy results in engaging higher numbers of people with HIV (PWH) who are virally unsuppressed.

Design:
We develop a modeling study that simulates an HIV epidemic (transmission, disease progression, and viral evolution) over 6 years using an agent-based model followed by simulating PRE strategies. We investigate two PRE strategies where referrals are based on social network strategies (SNS) or sexual partner contact tracing (SPCT).

Methods:
We parameterize, calibrate, and validate our study using data from Chicago on Black sexual minority men to assess these strategies for a population with high incidence and prevalence of HIV. For each strategy, we calculate the number of PWH recruited who are undiagnosed or out-of-care (OoC) and the number of direct or indirect transmissions.

Results:
SNS and SPCT identified 256.5 [95% confidence interval (CI) 234–279] and 15 (95% CI 7–27) PWH, respectively. Of these, SNS identified 159 (95% CI 142–177) PWH OoC and 32 (95% CI 21–43) PWH undiagnosed compared with 9 (95% CI 3–18) and 2 (95% CI 0–5) for SPCT. SNS identified 15.5 (95% CI 6–25) and 7.5 (95% CI 2–11) indirect and direct transmission pairs, whereas SPCT identified 6 (95% CI 0–8) and 5 (95% CI 0–8), respectively.

Conclusion:
With no testing constraints, SNS is the more effective strategy to identify undiagnosed and OoC PWH. Neither strategy is successful at identifying sufficient indirect or direct transmission pairs to investigate transmission networks.
Noncontrast Myocardial Characterization in Acute Myocardial Infarction Using Electron Density Imaging
Authors: Rodriguez-Granillo Gaston A. , Cirio Juan , Vila Jose F. , Langzam Eran , Ivanc Thomas , Fontana Lucia , Descalzo Amalia , Rubilar Bibiana , Lylyk Pedro 
Published: October 2023

Purpose:
Spectral computed tomography (CT) enables improved tissue characterization, although virtually all research has focused on contrast-enhanced examinations. We hypothesized that changes in myocardial tissue related to acute myocardial infarction (AMI) might potentially be identified without the need for contrast administration using electron density (ED) imaging.

Patients and Methods:
This retrospective observational study involved a small series (n = 15) of patients admitted to our institution with a first AMI without signs of hemodynamic instability and identification of a culprit vessel with invasive coronary angiography during the same admission, who also underwent a noncontrast, low-dose chest CT using a dual-layer spectral CT scanner. Images were assessed in search of dark areas with low density on ED imaging, and the mean percentage ED relative to water (%EDW) was calculated.

Results:
Using a qualitative approach, ED assessment enabled the identification of 11/15 (73%) affected coronary territories, with a sensitivity of 73% (95% CI: 45; 92%) and a specificity of 87% (95% CI: 69; 96%). AMI segments showed significantly lower ED values than the remote myocardium (103.8 ± 0.8 vs 104.3 ± 0.6 %EDW, P < 0.0001), and a threshold below 103.9 %EDW had a sensitivity of 66% and specificity of 79% for the identification of AMI. In a control group of patients without a history of cardiovascular disease, none had areas with focal reduction of ED following the shape of the myocardial wall.

Conclusions:
In our preliminary series, ED imaging showed the potential to enable the identification of myocardial tissue changes related to AMI without iodinated contrast requirement.
Application of a Novel Miniaturized Histopathologic Microscope for Ex Vivo Identifying Cerebral Glioma Margins Rapidly During Surgery: A Parallel Control Study
Authors: Wu Weichi , Xie Baoshu , Zhang Xiaowei , Zheng Chen , Sun Huixin , Jiang Mingyang , Hu Tiefeng , Liu Xinman , Zhang Nu , He Kejun 
Published: October 2023

Purpose:
The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery.

Methods:
Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment.

Results:
The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant (P=0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue.

Conclusion:
Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.