bluuebunny/crossref_metadata_2025 huggingface dataset:
Baryonic imprints on DM haloes: the concentration–mass relation in the C amels simulations
Authors: (Jon) Shao M , Anbajagane D , Chang C
Published: June 2023

The physics of baryons in haloes, and their subsequent influence on the total matter phase space, has a rich phenomenology and must be well understood in order to pursue a vast set of questions in both cosmology and astrophysics. We use the Cosmology and Astrophysics with MachinE Learning Simulation (Camels) suite to quantify the impact of four different galaxy formation parameters/processes (as well as two cosmological parameters) on the concentration–mass relation, cvir−Mvir. We construct a simulation-informed non-linear model for concentration as a function of halo mass, redshift, and six cosmological/astrophysical parameters. This is done for two galaxy formation models, IllustrisTNG and Simba, using 1000 simulations of each. We extract the imprints of galaxy formation across a wide range in mass $M_{\rm vir}\in [10^{11}, 10^{14.5}] \, {\rm M}_\odot \, h^{-1}$ and in redshift z ∈ [0, 6] finding many strong mass- and redshift-dependent features. Comparisons between the IllustrisTNG and Simba results show the astrophysical model choices cause significant differences in the mass and redshift dependence of these baryon imprints. Finally, we use existing observational measurements of cvir−Mvir to provide rough limits on the four astrophysical parameters. Our non-linear model is made publicly available and can be used to include Camels-based baryon imprints in any halo model-based analysis.
Cosmic chronometers to calibrate the ladders and measure the curvature of the Universe. A model-independent study
Authors: Favale Arianna , Gómez-Valent Adrià , Migliaccio Marina
Published: June 2023

We use the state-of-the-art data on cosmic chronometers (CCH) and the Pantheon+compilation of supernovae of Type Ia (SNIa) to test the constancy of the SNIa absolute magnitude, M, and the robustness of the cosmological principle (CP) at z ≲ 2 with a model-agnostic approach. We do so by reconstructing M(z) and the curvature parameter Ωk(z) using Gaussian Processes. Moreover, we use CCH in combination with data on baryon acoustic oscillations (BAO) from various galaxy surveys (6dFGS, BOSS, eBOSS, WiggleZ, DES Y3) to measure the sound horizon at the baryon-drag epoch, rd, from each BAO data point and check their consistency. Given the precision allowed by the CCH, we find that M(z), Ωk(z), and rd(z) are fully compatible (at $\lt 68$ per cent C.L.) with constant values. This justifies our final analyses, in which we put constraints on these constant parameters under the validity of the CP, the metric description of gravity and standard physics in the vicinity of the stellar objects, but otherwise in a model-independent way. If we exclude the SNIa contained in the host galaxies employed by SH0ES, our results read $M=(-19.314^{+0.086}_{-0.108})$ mag, rd = (142.3 ± 5.3) Mpc, and $\Omega _k=-0.07^{+0.12}_{-0.15}$, with H0 = (71.5 ± 3.1) km s−1 Mpc−1 (68 per cent C.L.). These values are independent of the main data sets involved in the H0 tension, namely, the cosmic microwave background and the first two rungs of the cosmic distance ladder. If, instead, we also consider the SNIa in the host galaxies, calibrated with Cepheids, we measure $M=(-19.252^{+0.024}_{-0.036})$ mag, $r_\mathrm{ d}=(141.9^{+5.6}_{-4.9})$ Mpc, $\Omega _\mathrm{ k}=-0.10^{+0.12}_{-0.15}$, and $H_0=(74.0^{+0.9}_{-1.0})$ km s−1 Mpc−1.
Occupational arsenic exposure and genitourinary cancer: systematic review and meta-analysis
Authors: Sassano M , Seyyedsalehi M S , Siea A C , Boffetta P
Published: June 2023

Background

Existing evidence suggests that ingestion of high doses of arsenic through drinking water is associated with an increased risk of genitourinary cancers, while systematic evidence on workers exposed to arsenic is lacking.

Aims

The aim of this study is to systematically review the evidence on the association between occupational exposure to arsenic and genitourinary cancer risk and mortality.

Methods

A systematic literature search was carried out on Pubmed, Web of Science and Embase by including cohort and case–control studies. Study-specific relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using Mandel–Paule random-effects model. Contour-enhanced funnel plot and Egger’s test were used to assess the occurrence of publication bias.

Results

A total of 17 studies were included in the meta-analysis, 7 on cancer incidence (n = 161,244 individuals) and 10 on cancer mortality (n = 91,868). Most of them were cohort (71%) and industry-based studies (59%). The meta-analysis failed to detect an increased risk of genitourinary cancers among workers exposed to arsenic, except for a suggestive but not significant positive association for bladder cancer incidence (RR: 1.26, 95% CI: 0.89, 1.80), although this estimate was based on only three studies. No compelling evidence of publication bias was found (P = 0.885).

Conclusions

Our findings did not show an association between occupational exposure to arsenic and genitourinary cancers, although further high-quality studies with detailed exposure assessment at the individual level are needed to clarify this relationship.
NontyphoidalSalmonellaInvasive Disease: Challenges and Solutions
Authors: Crump John A , Nyirenda Tonney S , Kalonji Lisette Mbuyi , Phoba Marie-France , Tack Bieke , Platts-Mills James A , Gordon Melita A , Kariuki Samuel M
Published: June 2023

Nontyphoidal Salmonella are a leading cause of community-onset bacteremia and other serious infections in sub-Saharan African countries where large studies indicate that they are an uncommon cause of moderate-to-severe diarrhea. Approximately 535 000 nontyphoidal Salmonella invasive disease illnesses and 77 500 deaths were estimated to occur in 2017; 422 000 (78.9%) illnesses and 66 500 (85.9%) deaths in countries in sub-Saharan Africa. Lineages of Salmonella enterica serovar Typhimurium sequence type (ST) 313 and lineages of Salmonella enterica serovar Enteritidis ST11 dominate as causes of invasive disease. A major reservoir for these specific strains outside of humans has not been identified to date. Human fecal shedding of such strains is common in areas where nontyphoidal Salmonella invasive disease incidence is high. The case-fatality ratio of nontyphoidal Salmonella invasive disease is approximately 15%. Early diagnosis and treatment are needed to avert fatal outcomes. Antimicrobial resistance, including multiple drug resistance, decreased fluoroquinolone susceptibility, and resistance to third-generation cephalosporins, is increasing in prevalence and is likely to further compromise patient outcomes. Naturally acquired immunity against invasive disease develops in children aged >3 years in endemic areas, likely mediated in part by the sequential acquisition of T-cell immunity, followed by antigen-specific immunoglobulin G antibodies. Vaccines in preclinical or clinical development include live-attenuated S. enterica serovar Typhimurium, nontyphoidal S. enterica core and O-polysaccharide glycoconjugates, multiple antigen-presenting system complexes, and generalized modules for membrane antigens vaccines. The latter are in phase I trials in Europe and Africa. Both vaccine use, and other effective, evidence-based nonvaccine interventions, are needed to prevent and control nontyphoidal Salmonella invasive disease.
Seroepidemiology for Enteric Fever: Emerging Approaches and Opportunities
Authors: Aiemjoy Kristen , Seidman Jessica C , Charles Richelle C , Andrews Jason R
Published: June 2023

Safe and effective typhoid conjugate vaccines (TCVs) are available, but many countries lack the high-resolution data needed to prioritize TCV introduction to the highest-risk communities. Here we discuss seroepidemiology—an approach using antibody response data to characterize infection burden—as a potential tool to fill this data gap. Serologic tests for typhoid have existed for over a hundred years, but only recently were antigens identified that were sensitive and specific enough to use as epidemiologic markers. These antigens, coupled with new methodological developments, permit estimating seroincidence—the rate at which new infections occur in a population—from cross-sectional serosurveys. These new tools open up many possible applications for enteric fever seroepidemiology, including generating high-resolution surveillance data, monitoring vaccine impact, and integrating with other serosurveillance initiatives. Challenges remain, including distinguishing Salmonella Typhi from Salmonella Paratyphi infections and accounting for reinfections. Enteric fever seroepidemiology can be conducted at a fraction of the cost, time, and sample size of surveillance blood culture studies and may enable more efficient and scalable surveillance for this important infectious disease.
Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program
Authors: Birkhold Megan , Datta Shrimati , Pak Gi Deok , Im Justin , Ogundoyin Olakayode O , Olulana Dare I , Lawal Taiwo A , Afuwape Oludolapo O , Kehinde Aderemi , Phoba Marie-France , Nkoji Gaëlle , Aseffa Abraham , Teferi Mekonnen , Yeshitela Biruk , Popoola Oluwafemi , Owusu Michael , Nana Lady Rosny Wandji , Cakpo Enoch G , Ouedraogo Moussa , Ouangre Edgar , Ouedraogo Isso , Heroes Anne-Sophie , Jacobs Jan , Mogeni Ondari D , Haselbeck Andrea , Sukri Leah , Neuzil Kathleen M , Metila Octavie Lunguya , Owusu-Dabo Ellis , Adu-Sarkodie Yaw , Bassiahi Abdramane Soura , Rakotozandrindrainy Raphaël , Okeke Iruka N , Zellweger Raphaël M , Marks Florian
Published: June 2023

Background

Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria.

Methods

Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures.

Results

A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5–14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation.

Conclusions

Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.
Reliability, Validity, and Efficiency of an Item Response Theory–Based Balance Confidence Patient-Reported Outcome Measure
Authors: Deutscher Daniel , Kallen Michael A , Werneke Mark W , Mioduski Jerome E , Hayes Deanna
Published: June 2023

Objective

The aims of this study were to calibrate the original 16 items from the Activities-Specific Balance Confidence (ABC) Scale to create an item response theory (IRT)-based item bank and scoring metric of balance confidence (BC) and to assess psychometric properties of a computerized adaptive test (BC-CAT) and 6-item short-form (BC-SF) administration modes.

Methods

This retrospective study included data from patients who were treated in outpatient rehabilitation clinics and assessed for balance impairments by responding to the full ABC Scale at intake. IRT model assumptions of unidimensionality, local item independence, item fit, and presence of differential item functioning (DIF) were evaluated. BC-CAT-generated scores were assessed for reliability, validity, and administration efficiency, and the newly developed BC-SF was assessed for reliability.

Results

Total cohort included 20,354 patients (mean age [SD] = 66 [16] years; range = 14–89). All 16 items were retained in the final item bank based on support for unidimensionality and fit to the IRT model. No items demonstrated DIF. Reliability estimates were 0.95, 0.96, and 0.98 for the BC-SF, BC-CAT, and the full item bank, respectively. Scores discriminated among patient groups in clinically logical ways. After controlling for scores at intake, better outcomes were achieved for patients who were younger, had more acute symptoms, exercised more, and had fewer comorbidities. Scores were responsive to change with a moderate effect size, with negligible floor and ceiling effects. CAT scores were generated using an average of 4.7 items (median = 4) and correlated highly with full-bank scores (Pearson correlation coefficient = 0.99).

Conclusion

The IRT–based BC patient-reported outcome measure (PROM) was reliable, valid, moderately responsive to change, and efficient, with excellent score coverage. The measure is suitable for research and routine clinical administration using the BC-CAT or BC-SF administration modes. The full ABC Scale can be administered for increased clinical content when appropriate.

Impact

The newly developed BC-PROM was reliable and valid for assessing perceived BC. In addition, the BC-PROM has efficient administration modes with low patient response burden, which enhances feasibility and promotes use during routine clinical practice in busy rehabilitation settings. This study supports a transition to PROMs that are based on modern measurement approaches to achieve the combined benefits of high accuracy and efficiency.
The effect of diet-induced obesity on sleep and breathing in female mice
Authors: Kim Lenise J , Pho Huy , Anokye-Danso Frederick , Ahima Rexford S , Pham Luu V , Polotsky Vsevolod Y
Published: June 2023

Obesity and male sex are main risk factors for sleep-disordered breathing (SDB). We have shown that male diet-induced obesity (DIO) mice develop hypoventilation, sleep apnea, and sleep fragmentation. The effects of DIO on breathing and sleep architecture in females have not been investigated. We hypothesized that female mice are less susceptible to the detrimental effects of DIO on sleep and SDB compared to males. Female DIO-C57BL/6J and lean C57BL/6J mice underwent 24-hour metabolic studies and were exposed to 8% CO2 to measure the hypercapnic ventilatory response (HCVR), and sleep studies. Ventilatory response to arousals was calculated as ratio of the average and peak minute ventilation (VE) during each arousal relative to the baseline VE. Breathing stability was measured with Poincaré plots of VE. Female obesity was associated with decreased metabolism, indicated by reduced oxygen consumption (VO2) and CO2 production (VCO2). VE in 8% CO2 and HCVR were significantly attenuated during wakefulness. NREM sleep duration was reduced in DIO mice, but REM sleep was preserved. Ventilation during NREM and REM sleep was augmented compared to lean mice. Arousal frequency was similar between groups. Obesity increased the frequency of spontaneous arousals, whereas the apnea index was 4-fold reduced in DIO compared to lean mice. Obesity decreased pre- and post-apnea arousals. Obese mice had more stable breathing with reduced ventilatory response to arousals, compared to lean females. We conclude that obese female mice are protected against SDB, which appears to be related to an attenuated CO2 responsiveness, compared to the lean state.
Effects of bone marrow-derived mesenchymal stem cell transplantation in piglet Legg–Calve–Perthes disease models: a pilot study
Authors: Tomaru Yohei , Sugaya Hisashi , Yoshioka Tomokazu , Arai Norihito , Abe Tomoyuki , Tsukagoshi Yuta , Kamada Hiroshi , Yamazaki Masashi , Mishima Hajime
Published: June 2023

This preliminary study investigated the efficacy and safety of bone marrow-derived mesenchymal stem cell transplantation in a piglet Legg–Calve–Perthes disease (LCPD) model.

The LCPD model was induced in two Landrace piglets (6- and 7-week-old, weighing 12 and 17 kg, respectively) by ligaturing the femoral neck. In the first piglet, the natural LCPD course was observed. In the second piglet, 4 weeks after ligaturing the femoral neck, simple medium and medium containing 2.44 × 107 bone marrow-derived mesenchymal stem cells were transplanted into the right and left femoral heads after core decompression, respectively. Plain radiographs were obtained every 4 weeks, and the epiphyseal quotient was calculated by dividing the maximum epiphysis height by the maximum epiphysis diameter. The piglets were sacrificed at 14 weeks postoperatively. The femoral heads were extracted and evaluated grossly, pathologically, and by using computed tomography. The transplanted cell characteristics were evaluated using flow cytometry. Flattening of the epiphysis was observed in both femoral heads of the first piglet and only in the right hip of the second piglet. The epiphyseal quotients immediately and at 14 weeks postoperatively in the right femoral head of the second piglet were 0.40 and 0.14, respectively, while those of the left femoral head were 0.30 and 0.42, respectively. Hematoxylin and eosin staining did not reveal physeal bar or tumor cell formation. The transplanted cells were 99.2%, 65.9%, 18.2%, and 0.16% positive for CD44, CD105, CD29, and CD31, respectively. Core decompression combined with bone marrow-derived mesenchymal stem cell transplantation prevented epiphyseal collapse.
A Phase I Trial of the ABCB1 Inhibitor, Oral Valspodar, in Combination With Paclitaxel in Patients With Advanced Solid Tumors
Authors: Fracasso Paula M. , Fisher George A. , Goodner Sherry A. , Beumer Jan H. , Egorin Merrill J. , Fears Carole L. , Wildi Jonathan D. , Jones Gary J. , Pearce Tillman E. , Sikic Branimir I.
Published: June 2023

Objectives:

Multidrug resistance mediated by P-glycoprotein is a potential obstacle to cancer treatment. This phase 1 trial determined the safety of paclitaxel with valspodar, a P-glycoprotein inhibitor, in patients with advanced solid tumors.

Methods:

Patients were treated with single-agent paclitaxel Q3W 175 mg/m2 (or 135 mg/m2 if heavily pretreated) as a 3-hour infusion. If their disease was stable (SD) or progressive (PD), paclitaxel at 30% (52.5 mg/m2), 40% (70 mg/m2), or 50% (87.5 mg/m2) of 175 mg/m2 (full dose) was administered with valspodar 5 mg/kg orally 4 times daily for 12 doses. Pharmacokinetic sampling (PK) for paclitaxel and valspodar was performed during single-agent and combination therapy.

Results:

Sixteen patients had SD/PD after one cycle of paclitaxel and then received paclitaxel at 30% (n=3), 40% (n=3), and 50% (n=10) with valspodar. Hematologic adverse events (AEs) including myelosuppression at paclitaxel 40% were comparable to those of full-dose paclitaxel. Non-hematologic AEs consisted of reversible hepatic (hyperbilirubinemia and transaminitis) and neurologic AEs (ataxia and paresthesias). Eleven patients experienced SD with a median of 12.7 weeks (range, 5.4 to 36.0), 4 patients progressed, and 1 was inevaluable. Reduced dose paclitaxel with valspodar resulted in lower plasma peak concentrations of paclitaxel; otherwise, concentrations were similar to single-agent paclitaxel.

Conclusion:

Paclitaxel at 70 mg/m2 was administered safely with valspodar. Limited efficacy in hematologic and solid tumors resulted in discontinuation of its clinical development and other transporter inhibitors. Recently, the development of ATP-binding cassette transporter inhibitors has been reconsidered to mitigate resistance to antibody-drug conjugates.
A comprehensive echocardiographic analysis during simulated hypovolaemia
Authors: Feldheiser Aarne , Juhl-Olsen Peter , Nordine Michael , Stetzuhn Matthias , Wiegank Ludwig , Knebel Fabian , Treskatsch Sascha , Berger Christian
Published: June 2023

BACKGROUND

Peri-operative and critically ill patients often experience mild to moderate hypovolaemic shock with preserved mean arterial pressure (MAP), heart rate (HR) and decreased stroke volume index (SVI).

OBJECTIVES

The aim of this study was to evaluate echocardiographic parameters during simulated mild to moderate central hypovolaemia.

DESIGN

This was a prospective preclinical study.

SETTING

Laboratory trial performed in Charité-Universitätsmedizin Berlin, Germany.

PATIENTS AND METHODS

Thirty healthy male volunteers underwent graded central hypovolaemia using a lower body negative pressure (LBNP) chamber with a stepwise decrease to simulate a mild (−15 mmHg), mild-to-moderate (−30 mmHg), and moderate state of hypovolaemic shock (−45 mmHg). During every stage, a transthoracic echocardiography examination (TTE) was performed by a certified examiner.

MAIN OUTCOME MEASURES

Systolic and diastolic myocardial performance markers, as well as cardiac volumes were recorded during simulated hypovolaemia and compared to baseline values.

RESULTS

During simulated hypovolaemia via LBNP, SVI decreased progressively at all stages, whereas MAP and HR did not consistently change. Left ventricular (LV) ejection fraction decreased at −30 and −45 mmHg. Simultaneously with SVI decline, LV global longitudinal strain (LV GLS), tricuspid annular plain systolic excursion (TAPSE), and right ventricular RV S’ and left-atrial end-systolic volume (LA ESV) decreased compared to baseline at all stages.

CONCLUSIONS

In this study, simulated central hypovolaemia using LBNP did not induce consistent changes in MAP and HR. SVI decreased and was associated with deteriorated right- and left-ventricular function, observed with echocardiography. The decreased filling status was characterised by decreased LA ESV.

CLINICAL TRIAL NUMBER

ClinicalTrials.gov Identifier: NCT03481855.
Conservative Treatment of Fetal Goitrous Hypothyroidism Due to Thyroglobulin Mutations: A Case Report and Literature Review
Authors: Liu Shiping , Bai Wei , Gao Ying , Shi Chunyan , Fan Lixin , Chen Junya , Shi Jian , Sun Weijie , Hou Xinlin , Yang Huixia
Published: June 2023

With the advances in fetal medicine, there will be more cases of congenital hypothyroidism (CH) diagnosed in the fetal period. However, there is no consensus on the management protocol. We present a successful case of conservatively managed fetal goitrous hypothyroidism due to compound heterozygous TG mutations. Goiter was observed in a fetus at 23 weeks of gestation. Because there was no evidence of transplacental passage of antithyroid antibody and drugs, iodine overload, and iodine deficiency, the fetus was highly suspected to have CH. Considering the potential risks of amniocentesis/cordocentesis, and lack of available parenteral levothyroxine in China, the fetus was closely monitored thereafter. A male neonate was delivered vaginally without complications at 39 weeks of gestation. We verified severe hypothyroidism in the infant and immediately initiated levothyroxine therapy. His growth and mental development were normal at the age of 8 month. Whole-exome sequencing showed that the neonate had two compound heterozygous mutations in the TG gene. We also performed a literature review of the prognosis of postnatal treatment of CH due to TG mutations and the result showed that postnatal treatment of CH due to TG mutations has a favorable prognosis. However, further prospective studies are warranted to verify this conclusion.
Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus
Authors: Patel Arpan A. , Tapper Elliot B. , Kanwal Fasiha , Woodrell Christopher D. , Hansen Lissi , Lai Jennifer C. , Rogal Shari , McDermott Cara , Rakoski Mina , Ufere Nneka N.
Published: June 2023

Background:

Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.

Methods:

A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis.

Results:

The panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies.

Conclusion:

This expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.
Rho-associated protein kinase 1 inhibition in hepatocytes attenuates nonalcoholic steatohepatitis
Authors: Dohnalkova Ester , Bayer Rachel L. , Guo Qianqian , Bamidele Adebowale O. , Kim Lee Hyun Se , Valenzuela-Pérez Lucía , Krishnan Anuradha , Pavelko Kevin D. , Guisot Nicolas E.S. , Bunyard Peter , Kim Young-Bum , Ibrahim Samar H. , Gores Gregory J. , Hirsova Petra
Published: June 2023

Background:

NASH is the progressive form of NAFLD characterized by lipotoxicity, hepatocyte injury, tissue inflammation, and fibrosis. Previously, Rho-associated protein kinase (ROCK) 1 has been implicated in lipotoxic signaling in hepatocytes in vitro and high-fat diet-induced lipogenesis in vivo. However, whether ROCK1 plays a role in liver inflammation and fibrosis during NASH is unclear. Here, we hypothesized that pathogenic activation of ROCK1 promotes murine NASH pathogenesis.

Methods and Results:

Patients with NASH had increased hepatic ROCK1 expression compared with patients with fatty liver. Similarly, hepatic ROCK1 levels and activity were increased in mice with NASH induced by a western-like diet that is high in fat, fructose, and cholesterol (FFC). Hepatocyte-specific ROCK1 knockout mice on the FFC diet displayed a decrease in liver steatosis, hepatic cell death, liver inflammation, and fibrosis compared with littermate FFC-fed controls. Mechanistically, these effects were associated with a significant attenuation of myeloid cell recruitment. Interestingly, myeloid cell-specific ROCK1 deletion did not affect NASH development in FFC-fed mice. To explore the therapeutic opportunities, mice with established NASH received ROCKi, a novel small molecule kinase inhibitor of ROCK1/2, which preferentially accumulates in liver tissue. ROCK inhibitor treatment ameliorated insulin resistance and decreased liver injury, inflammation, and fibrosis.

Conclusions:

Genetic or pharmacologic inhibition of ROCK1 activity attenuates murine NASH, suggesting that ROCK1 may be a therapeutic target for treating human NASH.
Randomized Clinical Trial of Topical Insulin Versus Artificial Tears for Healing Rates of Iatrogenic Corneal Epithelial Defects Induced During Vitreoretinal Surgery in Diabetics
Authors: Dasrilsyah Aina Malindri , Wan Abdul Halim Wan Haslina , Mustapha Mushawiahti , Tang Seng Fai , Kaur Birinder , Ong Ee Yan , Bastion Mae Lynn Catherine
Published: June 2023

Purpose:

The aim of this study was to measure and compare the effect of topical insulin (0.5 units, 4 times per day) versus artificial tears (Vismed, sodium hyaluronate 0.18%, 4 times per day) for the healing of postoperative corneal epithelial defects induced during vitreoretinal surgery in diabetic patients.

Methods:

This is a double-blind randomized controlled hospital-based study involving diabetic patients with postoperative corneal epithelial defects after vitreoretinal surgery. Diabetic patients were randomized into 2 different groups and received either 0.5 units of topical insulin (DTI) or artificial tears (Vismed, sodium hyaluronate 0.18%; DAT). The primary outcome measured was the rate of corneal epithelial wound healing (mm2/h) over a preset interval and time from baseline to minimum size of epithelial defect on fluorescein-stained anterior segment digital camera photography. The secondary outcome measured was the safety of topical insulin 0.5 units and artificial tears (Vismed, sodium hyaluronate 0.18%). Patients were followed up until 3 months postoperation.

Results:

A total of 38 eyes from 38 patients undergoing intraoperative corneal debridement during vitreoretinal surgery with resultant epithelial defects (19 eyes per group) were analyzed. DTI was observed to have a significantly higher healing rate compared with the DAT group at rates over 36 hours (P = 0.010), 48 hours (P = 0.009), and 144 hours (P = 0.009). The rate from baseline to closure was observed to be significantly higher in the DTI group (1.20 ± 0.29) (mm2/h) compared with the DAT group (0.78 ± 0.20) (mm2/h) as well (P < 0.001). No adverse effect of topical insulin and artificial tears was reported.

Conclusions:

Topical insulin (0.5 units, 4 times per day) is more effective compared with artificial tears (Vismed, sodium hyaluronate 0.18%, 4 times per day) for the healing of postoperative corneal epithelial defects induced during vitreoretinal surgery in diabetic patients, without any adverse events.
Septic Arthritis and Multifocal Osteomyelitis Caused by Capnocytophaga canimorsus: A Case Report
Authors: Levy-Blitchtein Saul , Salmeron Paula , Rodriguez-Pardo Dolores , Corona Pablo , Amat Carles , Lung-Suarez Mayli
Published: June 2023

Microbiological diagnosis of chronic osteoarticular infections remains a major challenge, particularly when the clinical presentation is atypical and the pathogen is uncommon. In this unique case, Capnocytophaga canimorsus, a microorganism belonging to the oral microbiota of some domestic animals, caused septic arthritis and multifocal osteomyelitis in the long bone of a 43-year-old immunocompetent man. The patient was treated with two-stage surgery and local and systemic antibiotic therapy, and had a successful recovery. C. canimorsus should be considered as a possible etiological agent in patients with osteoarticular pathology and a history of exposure to domestic animals.
Analysis of Reported Adverse Events Related to Hemospray
Authors: Ahmed Khalid , Abdallah Mohamed , Abbas Daniyal , Jaber Fouad , Abdalla Abubaker O. , Mohamed Mouhand , McDonald Nicholas , Hanson Brian J. , Bilal Mohammad
Published: June 2023

Background:

Topical hemostatic powder is a mineral powder that forms an adherent barrier and coagulates active bleeding in the gastrointestinal (GI) tract. Hemospray is the first hemostatic powder approved by the Food and Drug Administration (FDA) in the United States. Hemospray has been increasingly used to manage GI bleeding. However, data on the adverse events of hemostatic powders are lacking. Therefore, we aim to report and analyze adverse events associated with Hemospray using the FDA’s “Manufacturer and User Facility Device Experience” database.

Methods:

We analyzed the postmarketing surveillance data from the FDA’s Manufacturer and User Facility Device Experience database for Hemospray, initially known as TC-325, from June 2018 through April 2022. Results of the search were classified into device-related technical issues, patient-related adverse events and health care staff-related adverse events.

Results:

Five hundred two medical device reporting claims were identified from June 2018 through April 2022. Seven duplicate claims were identified, and some claims included more than one event type. Therefore, there were 558 device-related problems, 28 patient-related adverse events, and 2 adverse events in health care staff members. The most common device-related problems were activation failure or failure to fire (n = 385, 70.0%) and obstruction of carbon dioxide flow (n = 121, 21.7). The most common patient-related adverse events included tissue injury or bleeding (n = 21) and perforation (n = 5).

Conclusion:

Although Hemospray is a valuable tool in the armamentarium for endoscopists in managing GI bleeding, endoscopists must be mindful of deice-related problems and potential patient-related adverse events.
Endoscopic-Directed Trans-Gastric Retrograde Cholangiopancreatography in Patients With Roux-en-Y gastric Bypasses
Authors: Su Tong , Chen Tianjie , Wang Jing , Feng Yuemin , Wang Ruixia , Zhao Shulei
Published: June 2023

Background and Aim:

Endoscopic ultrasound-directed trans-gastric retrograde cholangiopancreatography (EDGE) is a new procedure for treating pancreaticobiliary diseases in patients with Roux-en-Y gastric bypass (RYGB). The aim of this meta‑analysis was to determine the overall outcomes and safety of EDGE.

Materials and Methods:

We performed a computerized search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, through October 2022. The main outcome measures examined in the meta-analysis were technical and clinical success rates and overall adverse event (AE) rate, especially the lumen-apposing metal stent (LAMS) dislodgement rate. AE rates were assessed according to LAMS size (15 vs. 20 mm), number of stages (single vs. two) and access route (gastrogastric vs. jejuno-gastric).

Results:

Fourteen trials with a total of 574 patients who had undergone 585 EDGE procedures were included in this study. The cumulative technical and clinical success and AE rates were 98%, 94%, and 14%, respectively. The commonest AE was LAMS dislodgement (rate 4%). The overall AE rate was lower in the 20-mm LAMS than in the 15-mm LAMS group (odds ratio [OR]=5.79; 95% confidence interval [CI]: 2.35 to 14.29). There were no significant differences in AE rate between number of stages (OR=1.36; 95% CI: 0.51 to 3.64) or differing access routes (OR=1.03; 95% CI 0.48 to 2.22).

Conclusion:

We here provide evidence that EDGE for endoscopic retrograde cholangiopancreatography yields good treatment outcomes in patients with RYGBs. The AE rate is significantly lower with 20-mm versus 15-mm LAMS; thus, the former is likely preferable.
Responses of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers According to Outcomes of Symptom, Endoscopy, and Histology in Patients With Eosinophilic Esophagitis
Authors: Fujiwara Yasuhiro , Sawada Akinari , Ominami Masaki , Fukunaga Shusei , Otani Koji , Hosomi Shuhei , Nagami Yasuaki , Taira Koichi , Tanaka Fumio
Published: June 2023

Goals:

We aimed to examine the response rate to proton pump inhibitors (PPIs) and potassium-competitive acid blockers and the prevalence of topical corticosteroid (TCS) therapy as the second-line treatment for eosinophilic esophagitis (EoE).

Background:

Acid-suppressive drugs such as PPIs and potassium-competitive acid blockers are often used to treat EoE. Treatment response is based on outcomes including symptoms, endoscopy, and histology; however, the detailed response rate to PPI/P-CAB is unknown.

Study:

In total, 236 patients with histologically confirmed EoE who received PPI/P-CAB as the first-line treatment were included. We assessed the symptoms, endoscopic reference score (EREFS), and histology [eosinophils per high-power field (eos/hpf)] 8 weeks after PPI/P-CAB administration. Complete normalization was defined as the disappearance of symptoms, EREFS score 0, or 0–1 eos/hpf, and response as disappearance or improvement of symptoms, EREFS score ≤2, or <15 eos/hpf. The prevalence of TCS therapy in each response group was assessed.

Results:

Complete normalization was achieved in 25%, 50%, 36%, and 8% of patients for symptoms, endoscopy, histology, and all 3 outcomes, respectively. The response rates were 81%, 87%, 87%, 75%, and 60% for symptoms, endoscopy, histology, and all 3 outcomes, respectively. TCS use was significantly lower (8%) in patients who achieved response of all 3 outcomes than in other groups and was dependent on the number of outcomes with nonresponse.

Conclusions:

Complete normalization of symptoms, endoscopy, and histology using PPI/P-CAB is uncommon. Based on treatment efficacy by response/nonresponse, TCS was the secondary treatment in cases with an increase in the number of nonresponse outcomes.
Ketogenic diet in cancer management
Authors: Talib Wamidh H. , Al-Dalaeen Anfal , Mahmod Asma Ismail
Published: June 2023

Purpose of review

This review presents details about types of ketogenic diet (KD), anticancer mechanisms, and the use of KD in experimental and clinical studies. Studies summarized in this review provide a solid ground for researchers to consider the use of KD to augment conventional treatments.

Recent findings

KD is a dietary pattern composed of high fat, moderate proteins, and very-low-carbohydrate. This diet was suggested to have an anticancer effect and to augment conventional anticancer therapies. KD can target cancer cell by interfering with its metabolism without harming normal cells.

Several experimental and clinical studies support the use of KD as adjuvant therapy to treat different cancers.
Surgical outcome of locked facet in distractive flexion injury of the subaxial cervical spine: Single institution retrospective study
Authors: Lee Kang-San , Park Eugene J. , Min Woo-Kie
Published: June 2023

The optimal surgical treatment for patients suffering from distractive flexion injury of the subaxial cervical spine with a locked facet (LF) is unknown. Closed reduction via an anterior or posterior approach is a treatment option for LF. We examined the surgical outcomes of patients treated for locked facet distractive flexion injury (LF-DFI) in this case series, with a particular emphasis on the surgical approach and reduction maneuver. We retrospectively analyzed the patients with distractive flexion injury of the subaxial cervical spine who underwent surgery at our hospital between November 2006 and April 2021. Patients who did not have facet subluxation or dislocation or those who achieved LF reduction prior to skin incision were excluded from this study. The patients were divided into 2 groups based on their initial approach, anterior or posterior approach. Perioperative clinical outcomes, including the American Spinal Cord Injury Association scale score, radiological changes, and complications were analyzed. This study enrolled 12 patients with LF-DFI. Four and 8 patients underwent the anterior and posterior approaches, respectively. The LF was reduced using an anterior approach with traction between the vertebral bodies in the anterior approach group and using a posterior approach with partial facetectomy in the posterior approach group. The preoperative American Spinal Cord Injury Association scale scores were as follows: A, 1 patient; B, 1 patient; C, 3 patients; D, 4 patients; and E, 3 patients. Nine patients showed no neurologic deterioration after surgery, whereas 2 had an aggravated neurologic status. Postoperatively, patients who underwent posterior open reduction did not exhibit worsened neurologic symptoms, whereas 2 patients who underwent the anterior approach showed worsened neurologic symptoms. At the final follow-up, all patients achieved radiological fusion, and no complications other than neurologic deterioration were identified. In terms of worsening postoperative neurologic status, a posterior approach using partial facetectomy for LF reduction is considered a safer surgical technique than an anterior approach. To avoid iatrogenic intraoperative cord injury, we recommend posterior approach in patients with LF-DFI.
Causal effects of tea intake on multiple types of fractures: A two-sample Mendelian randomization study
Authors: Pu Bin , Gu Peng , Luo Lieliang , Yue Dan , Xin Qiao , Zeng Zhanpeng , Zheng Xiaohui , Luo WeiDong
Published: June 2023

Fracture is a global public health disease. Bone health and fracture risk have become the focus of public and scientific attention. Observational studies have reported that tea consumption is associated with fracture risk, but the results are inconsistent. The present study used 2-sample Mendelian randomization (MR) analysis. The inverse variance weighted method, employing genetic data from UK Biobank (447,485 cases) of tea intake and UK Biobank (Genome-wide association study Round 2) project (361,194 cases) of fractures, was performed to estimate the causal relationship between tea intake and multiple types of fractures. The inverse variance weighted indicated no causal effects of tea consumption on fractures of the skull and face, shoulder and upper arm, hand and wrist, femur, calf, and ankle (odds ratio = 1.000, 1.000, 1.002, 0.997, 0.998; P = .881, 0.857, 0.339, 0.054, 0.569, respectively). Consistent results were also found in MR-Egger, weighted median, and weighted mode. Our research provided evidence that tea consumption is unlikely to affect the incidence of fractures.
Meta-analysis of repetitive transcranial magnetic stimulation combined with task-oriented training on upper limb function in stroke patients with hemiplegia
Authors: Xi Xiaoming , Wang Hujun , Han Liang , Ding Mengmeng , Li Jinglu , Qiao Chenye , Zhang Linlin , Liu Zongjian , Qie Shuyan
Published: June 2023

Background:

To evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with task-oriented training (TOT) on upper limb function in stroke patients with hemiplegia.

Methods:

A systematic review and meta-analysis was performed using PRISMA guidelines. Computer searches of PubMed, Cochrane Library, Embase, Web of science, China Knowledge Network, Wanfang, and Wipu databases were conducted from the time of database creation to October 27, 2022. Clinical trials meeting the inclusion criteria were screened, with rTMS combined with TOT in the test group and other therapies in the control group. Literature screening and data extraction were performed independently by 2 investigators, and meta-analysis was performed using Stata software after quality evaluation of the literature.

Results:

Meta-analysis results showed that repeated transcranial magnetic stimulation combined with TOT was more effective in box and block test (I2 = 0%, P = .820, 95% confidence interval [CI] [−0.20, 0.88]), Fugl-Meyer Assessment (I
2 = 0%, P = .569, 95% CI [0.88, 1.26]), and modified Barthel Index (I
2 = 39.9%, P = .189, 95% CI [0.45, 1.03]) were not significantly different from controls, and the efficacy was significantly better in motor evoked potentials (I
2 = 86.5%, P < .001, 95% CI [−1.38, −0.83]).

Conclusions:

Data analysis clarified the efficacy of rTMS) combined with TOT on upper extremity motor function disorders after stroke, but there was no significant difference between the efficacy in box and block test, Fugl-Meyer Assessment, and modified Barthel Index and the efficacy in motor evoked potentials between rTMS and the control group, suggesting that the neuro plasticizing effect of rTMS may translate into functional improvement by promoting neuro electrical signaling.
Bioinformatic analysis of biological changes involved in pelvic organ prolapse
Authors: Wang Wei Guo , Chen Zhang Sen Di , Sun Ji , Yang Chun Mei , He Hong Bo , Lu Xian Kun , Wang Wei Yuan
Published: June 2023

The molecular mechanisms involved in the pathogenesis of pelvic organ prolapse (POP) remain unclear. This study aimed to identify key molecules involved in the pathogenesis and progression of POP. Differentially expressed genes (DEGs) were identified based on gene expression data extracted from the GSE53868, GSE28660, and GSE12852 datasets in the gene expression omnibus database. The R software was used for data mining, and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to explore the biological functions of DEGs. A protein–protein interaction network (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes database, and hub genes were identified by the Cytoscape plug-in cytoHubba. In addition, the CIBERSORT algorithm was used to analyze and evaluate immune cell infiltration in POP tissues. A total of 92 upregulated DEGs were identified and subjected to enrichment analysis. Gene ontology analysis revealed that these DEGs were associated with response to hormones, positive regulation of cell death, collagen-containing extracellular matrix, and extracellular matrix. Kyoto encyclopedia of genes and genomes pathway analysis showed that the upregulated genes were mainly enriched in the phosphatidylinositol 3-kinase–AKT signaling pathway. The PPI network was structured. Nodes in the PPI network were associated with structural molecular activity and collagen-containing extracellular matrix. A total of 10 hub genes were identified, namely, CDKN1A, IL-6, PPARG, ADAMTS4, ADIPOQ, AREG, activating transcription factor 3, CCL2, CD36, and Cell death-inducing DNA fragmentation factor-like effector A. Furthermore, patients with POP were found to have a higher abundance of CD8-positive T cells in the 3 gene expression omnibus datasets. The abundance of CD8-positive T cells was negatively correlated with that of follicular helper T cells (Pearson correlation coefficient = −0.34, P < .01) or gamma delta T cells (Pearson correlation coefficient = −0.33, P < .01). But was positively correlated with that of M2 macrophages (Pearson correlation coefficient = 0.35, P < .01) and activated memory CD4 T cells (Pearson correlation coefficient = 0.34, P < .01). Altogether, PPARG, ADAMTS4, ADIPOQ, AREG, CD36, and Cell death-inducing DNA fragmentation factor-like effector A genes were discovered in the POP process for the first time, which should be intensively investigated.
Anterior fontanel size in Korean nursery newborns and clinical implications of large anterior fontanel: A retrospective cohort, observational study
Authors: Cho Kee Hyun , Kim Ja Kyoung , Kim Eun Sun
Published: June 2023

Anterior fontanel (AF) sizes in newborns are influenced by ethnicity, gender, genetics, nutrition, and other pathological conditions. However, AF sizes in recent Korean newborns have not been reported yet. Thus, this study aimed to understand variation in AF size and clinical implications of large AF sizes in newborns. This cohort study was conducted on nursery newborns born at a University Hospital between September 2019 and August 2020. AF size was measured at 24 to 48 hours after birth. Newborns with a large AF (> 3.6cm) were examined for other pathological reasons using radiological and laboratory tests. Demographic data were analyzed in relation to AF size. A total of 573 newborns were investigated. Their mean gestational age was 38.5 ± 1.2 weeks at birth and their mean birth weight was 3140 ± 450 g. Their mean AF size was 1.85 ± 0.83 cm (90 and 97-percentile of AF size were 2.96 and 3.65 cm, respectively). Among demographic factors, small for gestational age (SGA) weight, SGA head circumference, and multiple births were correlated with larger AF size. Among 18 infants with a large AF, 2 had intracranial abnormalities and 11 had vitamin D deficiency. This is the first recent study on AF sizes of Korean newborn infants. Their mean AF size was the smallest so far. For the largest AF size, a cutoff of 3.65 cm met the 97-percentile of the cohort. Both SGA weight and head circumference were risk factors for large AF size. For the largest AF size, intracranial lesions and vitamin D deficiency as well as SGA presented clinical implications.