bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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.

Summary
Several experimental and clinical studies support the use of KD as adjuvant therapy to treat different cancers.