bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant probiotic Bifidobacterium animalis subsp. lactis CP-9 improve phototherapeutic treatment outcomes in neonatal jaundice among full-term newborns: A randomized double-blind clinical study
Authors: Tsai Ming-Luen , Lin Wen-Yang , Chen Yin-Ting , Lin Hsiang-Yu , Ho Hsieh-Hsun , Kuo Yi-Wei , Lin Jia-Hung , Huang Yen-Yu , Wang Hui-Shan , Chiu Hsiao-Yu , Lin Hung-Chih
Published: November 2022

Background:

Probiotics had been used to decreased bilirubin level in neonatal jaundice (NJ) without being further studied mechanism and stratification. The intestinal pathogen Escherichia coli produced β-glucuronidase would increase enterohepatic circulation and elevate serum bilirubin levels (SBLs) which might worsen the disease process of NJ.

Study objective:

We hypothesized that some probiotics could decrease bilirubin level through inhibiting the growth of E. coli. It’s assumed that adjuvant probiotic intervention might accelerate the phototherapy for NJ and alleviate the severity of the NJ. Besides, it’s further study the efficacy of the probiotic intervention in NJ among the full-term and preterm newborns.

Materials and methods:

Firstly, the Bifidobacterium animalis subsp. lactis CP-9 was screened for its anti-E. coli activity. Then, it was orally administered to newborns with NJ in combination with conventional phototherapy (wavelength 425–457 nm) to determine its efficacy. 83 neonatal patients whose serum bilirubinemia was at a concentration of ≥ 15 mg/dL were participated the double-blind randomized trial and conducted in the neonatal ward of China Medical University Children’s Hospital (CMUCH, Taichung, Taiwan). The test was conducted in 2 groups: experimental group: phototherapy + B. animalis subsp. lactis CP-9 (n = 43; 5 × 109 CFU/capsule) and control group: phototherapy + placebo (n = 40). The SBL and total phototherapy duration were measured.

Results:

The experimental group showed improved serum bilirubin decline rate (−0.16 ± 0.02 mg/dL/h; P = .009, 95% CI -0.12 to -0.2), particularly in the first 24 hour of in-hospital care, and reduced total phototherapy duration (44.82 ± 3.23 h; P = .011, 95% CI: 51.3–38.2) compared with the control group. Especially, probiotics had a significant therapeutic effect (serum bilirubin decline rate: −0.18 ± 0.02 mg/dL/h, 95% CI -0.12 to -0.23, P = .014; phototherapy duration: 43.17 ± 22.72 h, 95% CI 51.9–34.3, P = .019) in the low-risk subgroup (full-term newborns).

Conclusions:

In conclusion, B. animalis subsp. lactis CP-9 synergistically improves treatment outcomes of NJ during in-hospital phototherapy including reduced total phototherapy duration and improved serum bilirubin decline rate, particularly in full-term newborns.
Metabolic outcomes in patients with type 2 diabetes mellitus after metabolic management center
Authors: Li Xia , Bai Xiaogang , Wang Jing , Bai Ting , Zhu Yali , Li Sheli , Ren Wenjing , Niu Xiaoling , Zheng Jiayin , Kou Changqin
Published: November 2022

The Chinese Medical Doctor Association has initiated metabolic management center (MMC) program for 6 years since 2016 nationwide. It is worth investigating the level of control metabolic outcomes in patients with type2 diabetes (T2DM) after MMC model in Yan’an, northwest China. Patients with T2DM was admitted to MMC in Yan’an University Affiliated Hospital from November 2018 to July 2021. They were asked to revisit hospital every 3 months. Blood glucose, blood pressure and blood lipids at baseline were compared to its counterparts after 1 year MMC management. Glycosylated hemoglobin and low density lipoprotein cholesterol (LDL-C) level in T2DM patients after 1 year management were lower than their baseline level (glycosylated hemoglobin 7.74 ± 1.94% vs 8.63 ± 2.26%, P < .001; LDL-C 1.81 ± 0.73mmol/L vs 2.18 ± 1.49mmol/L, P < .001). Mean HOMA-β increased after management (65.89 ± 90.81% vs 128.38 ± 293.93%, P < .05). After 1 year of management, patients in high school or above group achieved higher control rate of body mass index than those in middle school or below group (71.82% vs 28.18%, P = .043). high density lipoprotein cholesterol control rate was higher in high income group (42.86% vs 34.97%, 16.28%, P = .012), while LDL-C control rate was higher in low-income group (97.67% vs 78.57%, 84.51%, P = .018). fasting plasma glucose control rate in new diagnosis group was higher than that of the middle and long course groups (71.43% vs 52.38%, 42.44%, P = .002). The comprehensive control rate increased from 9.83% at baseline to 26.15% after 1 year MMC management. The metabolic outcomes and their control rate in T2DM patients were improved after 1 year MMC management. It indicated that patients may achieve more benefits with MMC management.
Clinical study of multifunctional laryngeal mask in airway interventional therapy
Authors: Zhou Yuan , Peng Jianliang , Zhu Wujian , Ke Yazhen , Shan Ligang
Published: November 2022

Objective:

This study is conducted to evaluate the efficacy and safety of using multifunctional intubation laryngeal masks with normal frequency jet ventilation in airway interventional therapy.

Methods:

A total of 200 patients receiving airway interventional therapy were enrolled in this retrospective study and were divided into 2 groups (group M and group P) by doctors in our hospital to compare the effect of different laryngeal masks. Group M used common laryngeal masks and an anesthesia machine for positive pressure ventilation while group P took multifunctional intubation laryngeal masks and used a jet ventilator for normal frequency jet ventilation. The patients’ mean arterial pressure, heart rate, arterial oxygen partial pressure (PaO2) and arterial carbon dioxide partial pressure (PaCO2), and the operation time, recovery score and the patients’ and doctors’ satisfaction levels were compared between the 2 groups.

Results:

Both groups were hemodynamically stable, and their PaO2 levels were significantly higher before the operation than that during and after the operation (P < .05). Compared with group M, the PaCO2 level of group P was more stable both during and after the operation, and this difference was statistically significant (P < .05). There was no statistically significant difference in terms of the 2 group’s operating time, recovery score, and patients’ satisfaction levels (P > .05). However, the satisfaction levels of doctors in group P were higher than that in group M, and this difference was statistically significant (P < .05).

Conclusion:

As statistics show, the intraoperative hemodynamics and PaO2 and PaCO2 levels were stable, and patients, surgeons and anesthesia operators were satisfied. Therefore, it is feasible to apply multifunctional intubation laryngeal masks with normal frequency jet ventilation in airway interventional therapy and it is a safe and ideal way to ensure ventilation.
Herbal medicine and acupuncture relieved progressive bulbar palsy for more than 3 years: A case report
Authors: Peng Siyang , Chang Weiqian , Tian Yukun , Yang Yajing , Li Shaohong , Ni Jinxia , Zhu Wenzeng
Published: November 2022

Rationale:

Progressive bulbar palsy (PBP) is a type of motor neuron disease (MND). The main symptoms include dysarthria, dysphagia, tongue muscle atrophy and fasciculations. This disease is generally severe and develops rapidly. Due to the lack of effective treatment, many patients with MND in China turn to traditional Chinese medicine treatment for help. We successfully relieved dysphagia and sialorrhea in a patient with PBP for 3 years with herbal medicine and acupuncture.

Patient concerns:

The patient was a 68-years-old woman with PBP and suffered from severe dysphagia and sialorrhea.

Diagnoses:

Progressive bulbar palsy.

Interventions:

Chinese herbal medicine and acupuncture.

Outcomes:

After 4 months of herbal medicine and acupuncture treatment, dysphagia and sialorrhea were relieved considerably. The patient’s condition has been stable for more than 3 years and continues to be treated with Chinese herbal medicine and acupuncture.

Lessons:

Our case suggests that alternative therapies such as herbal medicine and acupuncture may be effective in alleviating the symptoms of MND/PBP. However, standardized clinical studies are still required to verify the effectiveness and safety.
Effects of acupuncture combined with medication on patients with COVID-19 complicated with bipolar disorder: A protocol of systematic review and meta-analysis
Authors: Huang Wenjing , Zhu Luwen , Wu Minmin , Teng Lili , Zhang Mei , Song Wenjing
Published: November 2022

Background:

There is growing evidence that coronavirus disease 2019 (COVID-19) can trigger acute episodes of mood disorders or psychotic symptoms. Reports on the treatment of COVID-19-related bipolar disorder (BD) are limited. Our study aimed to investigate the potential for new or recurrent BD due to COVID-19. We qualitatively evaluate clinical treatments (acupuncture combined with medication) and any potential pathophysiological links between infection and BD.

Methods:

We searched Embase, PubMed, Cochrane Library, Web of Science and MEDLINE (via Web of Science), Scopus, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database, and the Wanfang Database from December 1, 2019, to September 15, 2022, to identify all articles on acupuncture combined with drugs used to treat COVID-19 complicated with bipolar disorders. Two researchers will screen the articles and extract the relevant information.

Results:

The results will provide a systematic overview of the current evidence on the use of acupuncture combined with drug therapy to treat COVID-19 complicated with bipolar disorder.

Conclusion:

The conclusions of this study will help clarify the effects of acupuncture combined with drug therapy on patients with COVID-19-related BD.
Successful control of scleritis caused by Nocardia farcinica: A case report
Authors: Hao Zhongkai , Dang Hui , Gao Xin , Zhang Chenming , Deng Aijun , Tan Yue , Ding Gang
Published: November 2022

Rationale:

Nocardia farcinica is an opportunistic pathogen that rarely causes ocular infections. This study reviewed a case of N. farcinica-mediated scleritis involving the corneal limbus.

Patient concerns:

A 56-year-old man was admitted to the Department of Keratology of Jinan Second People’s Hospital due to “a red and swollen right eye accompanied with severe pain for >1 month.” He denied any history of hypertension, diabetes, systemic immune diseases and eye surgery.

Diagnoses:

Corneal defect and scleral necrosis were observed by slit lamp. Combination of anterior segment optical coherence tomography and ophthalmic ultrasound biomicroscopy was used for diagnosis and evaluation of corneal and scleral conditions. Culture and metagenomic sequencing verified that the pathogen of scleritis was N. farcinica.

Interventions:

The patient was treated by sulfacetamide sodium eye drops, oral administration of sulfamethoxazole tablets, amikacin anterior chamber flushing, scleral debridement, and allogeneic scleral transplantation.

Outcomes:

The disease was successfully controlled.

Lessons:

Infectious scleritis caused by N. farcinica is extremely rare. Culture of pathogenic microorganisms remains to be the gold standard for the diagnosis of infectious eye diseases. Metagenomic sequencing shows potential promise in the diagnosis of infectious eye diseases. N. farcinica is sensitive to sulfonamides and amikacin.
Serum kisspeptin levels in deep-infiltrating, ovarian, and superficial endometriosis: A prospective observational study
Authors: Önal Mesut , Karli Pervin , Özdemir Ayşe Zehra , Kocaman Adem , Katirci Yunus , Çoban Gülnur , Nakişli Gülen Kübra , Civil Yeşim , Avci Bahattin
Published: November 2022

The diagnosis of endometriosis may delay for many years due to non-deterministic symptoms and avoiding surgical interventions. Kisspeptins are hormones that interact with endometrial tissue to limit invasions during placentation and various cancers and are suggested to be also associated with endometriosis. This study evaluated if serum kisspeptin levels are associated with the invasion depth in endometriosis. Forty patients between 18 and 45 years of age and admitted to a tertiary-care Obstetrics and Gynecology Department between 2020 and 2021 with a diagnosis of endometriosis, and 40 patients without endometrioma were included in the study. Demographic, obstetric, clinical, and biochemical characteristics were evaluated in patients with superficial (SE) and deep infiltrating (DIE) endometriosis and healthy controls. Twenty patients (50%) had SE, 14 (35%) had DIE, and 22 (55%) had endometrioma in the patient group. Fertility rates were higher among controls, but similar between patients with SE and DIE. CA125 levels were significantly higher in the DIE group. SE and DIE groups had similar kisspeptin values, significantly higher than controls. CA125 and kisspeptin levels were not correlated in study groups. Serum kisspeptin levels were significantly different between endometriosis patients and healthy controls. However, kisspeptin levels were unable to differentiate endometriosis severity. Our results suggest that kisspeptins might play a role in the pathogenesis of endometriosis, which needs further assessment in more comprehensive studies.
Early antiviral and supervisory dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 patients
Authors: Sitasuwan Tullaya , Phisalprapa Pochamana , Srivanichakorn Weerachai , Washirasaksiri Chaiwat , Auesomwang Chonticha , Tinmanee Rungsima , Sayabovorn Naruemit , Chayakulkeeree Methee , Phoompoung Pakpoom , Mayurasakorn Korapat , Sookrung Nitat , Tungtrongchitr Anchalee , Wanitphakdeedecha Rungsima , Muangman Saipin , Senawong Sansnee , Tangjittipokin Watip , Sanpawitayakul Gornmigar , Woradetsittichai Diana , Nimitpunya Pongpol , Kositamongkol Chayanis , Nopmaneejumruslers Cherdchai , Vamvanij Visit , Chaisathaphol Thanet
Published: November 2022

This study aimed to evaluate the efficacy of early antiviral treatment in preventing clinical deterioration in asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 infected (COVID-19) patients in home isolation and to share our experiences with the ambulatory management of nonsevere COVID-19 patients. This retrospective study included mild COVID-19 adult patients confirmed by real-time reverse transcription-polymerase chain reaction. They received care via an ambulatory management strategy between July 2021 and November 2021. Demographic data, clinical progression, and outcomes were collected. Both descriptive and inferential statistics were performed to illustrate the cohort’s characteristic and outcomes of the study. Univariable and multivariable logistic regression models were employed to investigate the associations between clinical factors and disease progression. A total of 1940 patients in the Siriraj home isolation system met the inclusion criteria. Their mean age was 42.1 ± 14.9 years, with 14.2% older than 60 years, 54.3% female, and 7.1% with a body weight ≥ 90 kg. Only 115 patients (5.9%) had deterioration of clinical symptoms. Two-thirds of these could be managed at home by dexamethasone treatment under physician supervision; however, 38 of the 115 patients (2.0% of the study cohort) needed hospitalization. Early favipiravir outpatient treatment (≤ 5 days from onset of symptoms) in nonsevere COVID-19 patients was significantly associated with a lower rate of symptom deterioration than late favipiravir treatment (50 [4.6%] vs 65 [7.5%] patients, respectively; P = .008; odds ratio 1.669; 95% confidence interval, 1.141–2.441). The unfavorable prognostic factors for symptom deterioration were advanced age, body weight ≥ 90 kg, unvaccinated status, higher reverse transcription-polymerase chain reaction cycle threshold, and late favipiravir treatment. The early delivery of essential treatment, including antiviral and supervisory dexamethasone, to ambulatory nonsevere COVID-19 patients yielded favorable outcomes during the COVID-19 pandemic in Thailand.
Low-grade myofibroblastic sarcoma of the proximal femur: A case report and literature review
Authors: Gao Guanying , Liu Yuhao , Ao Yingfang , Wang Jianquan , Xu Yan
Published: November 2022

Rational:

Low-grade myofibroblastic sarcoma (LGMS) is an atypical type of tumor composed of myofibroblasts. LGMS in the femoral head neck junction is extremely rare and no case treated by hip arthroscopy was reported.

Patient concerns:

We reported a case of LGMS in the femoral head neck junction treated by hip arthroscopy. A 30-year-old female was admitted to our hospital with discomfort and pain after left hip sprained one year prior. Physical examination revealed swelling of the left hip and magnetic resonance images showed a soft tissue mass in the femoral head neck junction.

Diagnosis:

Via microscopy of pathological specimens, spindle cell proliferative lesions, atypia of some cells, and mitotic figures/pathological mitotic figures of some cells were observed. Immunohistochemistry revealed positive for smooth muscle actin, focally positive for CD34 and CD68, while negative for S-100, desmin, and anaplastic lymphoma kinase. The imaging, histomorphological and immunohistochemical features suggested a final diagnosis of LGMS of the proximal femur.

Interventions:

This patient underwent hip arthroscopy for excision of the soft tissue mass.

Outcomes:

The clinical and imaging follow-up at 6 months postoperatively showed that surgery had achieved good clinical outcomes.

Lessons:

To the best of our knowledge, this is the first case report of LGMS in the femoral head neck junction treated by hip arthroscopy. Beyond the present case, other 120 cases from 58 literatures (1998–2022) are reviewed and discussed. The age of LGMS patients ranged from 11 months to 77 years and the male-to-female ratio was approximately 1.28:1. The location distribution of previously reported LGMS cases and the present case was as follows: Head&neck (45.90%), trunk (30.33%), and extremity (23.77%). Hip arthroscopic excision of LGMS may achieve relatively good clinical outcomes.
Intrahepatic hematoma secondary to transjugular intrahepatic portosystemic stent–shunt procedure: Case report and literature review
Authors: Cheng Ziyao , Ju Jiayu , Zhu Qingliang , Deng Mingming , Zhang Hailong
Published: November 2022

Rationale:

Transjugular intrahepatic portosystemic stent–shunt (TIPSS) is a minimally invasive procedure used for the treatment of portal hypertension. Intrahepatic hematoma is the rare complication caused by hepatic arterial injuries from TIPSS procedure.

Patient concerns:

This case report illustrated a 77-year-old man with hepatitis B virus-induced cirrhosis who underwent TIPSS.

Diagnoses:

The patient suffered from intrahepatic hematoma and hepatic pseudoaneurysm because of the hepatic artery injury after TIPSS.

Interventions:

The hepatic artery laceration began at the level of the branch of the left hepatic artery was embolized.

Outcomes:

The acute intrahepatic hematoma and hepatic pseudoaneurysm of the patient were cured.

Conclusion:

In this report, we describe a cirrhosis patient with a large intrahepatic hematoma secondary to TIPSS, and a literature review is also presented. The intrahepatic hematoma and hepatic pseudoaneurysm should be paid more attention after TIPSS while early-stage prevention should be carried out.
Japanese pediatric patient with refractory steroid-resistant ulcerative colitis successfully treated with Tofacitinib: A case report
Authors: Kakiuchi Toshihiko , Yoshiura Masato
Published: November 2022

Rationale:

Tofacitinib is an orally administered selective Janus kinase inhibitor. Its efficacy and safety in adults with moderately to severely active ulcerative colitis (UC) have been evaluated in clinical trials; however, its efficacy in pediatric patients with UC is limited.

Patient concerns:

A 9-years-old boy was referred to our hospital with chief complaints of diarrhea and bloody stool for 2 months. Colonoscopy revealed total colitis-type UC. His pediatric UC activity index score was 40, indicating moderately active UC.

Diagnosis:

UC.

Interventions:

Vedolizumab, golimumab, and ustekinumab were introduced because of steroid-resistant refractory UC; however, none of these biologics were effective or the effect was short-lived. Therefore, tofacitinib was administered 5 mg twice a day.

Outcomes:

The patient achieved UC remission after tofacitinib treatment, leading to maintained remission without adverse events.

Lessons:

To the best of our knowledge, this is the first pediatric case of moderately active UC that was successfully treated with tofacitinib in Japan. Tofacitinib is a safe drug for pediatric patients with moderately active UC. Even in steroid-dependent cases refractory to other biologics, tofacitinib can result in remission induction and maintenance effects. In children and adults, high-dose tofacitinib during induction therapy may be unnecessary to reduce adverse events.
Comparison arthroscopic reconstruction and percutaneous reconstruction of ankle lateral ligament for chronic ankle lateral instability: A protocol for a meta-analysis of comparative studies
Authors: Hou Huiming , Zhou Ming , Zhou Xing , Guo Wenxuan , Zhuang Rujie , Yin Hong , Li Jinlei
Published: November 2022

Background:

Ankle sprains occur very frequently in daily life, but people who do not pay attention to them and do not receive proper diagnosis and treatment are very prone to develop chronic ankle lateral instability (CALI) at a later stage. For CALI where conservative treatment has failed, reconstruction of the lateral collateral ligament of the ankle can achieve satisfactory results, but there are various and controversial ways of ligament reconstruction. While percutaneous reconstruction of ankle lateral ligament (PLCLR) needs to be performed repeatedly under fluoroscopy, total arthroscopic reconstruction of ankle lateral ligament (ALCLR) is increasingly recognized by experts and scholars for its minimally invasive and precise characteristics, and has achieved good clinical results. Therefore, it is imperative that a meta-analysis be performed to provide evidence as to whether there is a difference between ALCLR and PLCLR in the treatment of CALI.

Methods:

We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure, Wanfang Data, Chinese Scientific Journals Database, Chinese databases SinoMed, PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to September 2022.We will apply the risk-of-bias tool of the Cochrane Collaboration for Randomized Controlled Trials to assess the methodological quality. Risk-of-Bias Assessment Tool for Non-randomized Studies was used to evaluate the quality of comparative studies. Statistical analysis will be conducted using RevMan 5.4 software.

Results:

This systematic review will evaluate the functional outcomes and radiographic results of ALCLR in the treatment of CALI.

Conclusion:

The conclusion of this study will provide evidence for judging whether ALCLR is superior to PLCLR for treatment of CALI.

Trial registration number:

CRD42022362045.
A Phase II Study of Ziv-Aflibercept in Patients With Advanced Extrapancreatic Neuroendocrine Tumors
Authors: Perez Kimberly , Kulke Matthew H. , Horick Nora K. , Regan Eileen , Graham Christopher , Scheutz Samantha , Stonely Danielle , Enzinger Peter C. , Fuchs Charles S. , Allen Jill N. , Enzinger Andrea C. , Clark Jeffrey W. , Chan Jennifer A.
Published: November 2022

Objectives

Neuroendocrine tumors (NETs) are characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of Ziv-aflibercept, a recombinant protein that binds to and inhibits the activity of VEGF, in patients with advanced NETs (NCT01782443).

Methods

A single-arm, phase II trial enrolling patients with advanced, progressive extrapancreatic NET. Patients were treated with Ziv-aflibercept 4 mg/kg intravenously on day 1 and 15 of a 28-day cycle; the starting dose was reduced to 2 mg/kg on days 1 and 15 of a 28-day cycle because of hypertension-related events. The primary end point was progression-free survival.

Results

The trial enrolled 19 patients (13 male:6 female). Patients received a median of 7 cycles (range, 1–18 cycles). The median progression free survival was 11.8 months (95% confidence interval, 3.2–16.1 months), and the median overall survival was 36.4 months (95% confidence interval, 16.1–not reached). Best responses by Response Evaluation Criteria in Solid Tumors 1.1 are as follows: 1 (5%) partial response, 13 (68%) stable disease, 2 (10%) with progressive disease, and 3 (15%) unevaluable. Hypertension occurred in 18 patients (95%), including grade 3–4 hypertension in 12 patients (63%).

Conclusions

Although the progression free survival is similar to other VEGF inhibitors in NET, toxicity may preclude further investigation.
Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis
Authors: Hart Phil A. , Andersen Dana K. , Lyons Erica , Cote Gregory A. , Cruz-Monserrate Zobeida , Dworkin Robert H. , Elmunzer B. Joseph , Fogel Evan L. , Forsmark Christopher E. , Gilron Ian , Golden Megan , Gozu Aysegul , McNair Lindsay , Pandol Stephen J. , Perito Emily R. , Phillips Anna Evans , Rabbitts Jennifer A. , Whitcomb David C. , Windsor John A. , Yadav Dhiraj , Palermo Tonya M.
Published: November 2022

Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases–sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.
Salivary Biomarker Evaluation of Chronic Pancreatitis Patients Reveals Alterations in Human Proteins, Cytokines, Prostaglandin E2 Levels, and Bacterial Diversity
Authors: Waldron Richard T. , Jones Elaina K. , Anani Vincent I. , Hines Jolaine M. , Zhao Jing , Lugea Aurelia , Diniz Marcio A. , Kim Sungjin , Habtezion Aida , Hoffman Kristi L. , Petrosino Joseph F. , Fisher William E. , Li Liang , Lennon Ryan J. , Singh Ravinder Jit , Vege Santhi Swaroop , Pandol Stephen J. , Topazian Mark D.
Published: November 2022

Objectives

Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified.

Methods

Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls.

Results

Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90.

Conclusions

Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring.
Open-Source Ultrasound Trainer for Healthcare Professionals
Authors: Morrison Ryan G. , Halpern Sophie A. , Brace Eamonn J. , Hall Arielle J. , Patel Dip V. , Yuh Jonathan Y. , Brolis Nils V.
Published: November 2022

Introduction

This technical report describes the development of a high-fidelity, open-source ultrasound trainer and showcases its abilities through a proof-of-concept, pilot randomized control trial. The open-source ultrasound trainer (OSUT) aims to enhance anatomical visualization during ultrasound education. The OSUT can attach to any ultrasound transducer, uses minimal hardware, and is able to be used during live patient ultrasound examinations.

Methods

After viewing a standardized training video lecture, 24 incoming first-year medical students with no prior ultrasound experience were randomized into a control group given an ultrasound system or an intervention group given the OSUT in addition to an ultrasound system. Both groups were tasked with localizing the thyroid, abdominal aorta, and right kidney on a patient. Performance outcomes were structure localization time, ultrasound image accuracy, and preactivity and postactivity participant confidence.

Results

The OSUT decreased right kidney localization time (Kruskal-Wallis, P < 0.001), increased sonographer right kidney accuracy ratings (Mann-Whitney U, U = 10.5, P < 0.05), and increased confidence in structure identification (Mann-Whitney U, U = 37, P = 0.045) and overall ultrasound ability (Wilcoxon signed-rank test, P = 0.007). There was no significant change in localization time, accuracy ratings, or participant confidence for locating the thyroid and abdominal aorta.

Conclusions

A high-fidelity, open-source ultrasound trainer was developed to aid healthcare professionals in learning diagnostic ultrasound. The study demonstrated the potential beneficial effects of the OSUT in localizing the right kidney, showcasing its adaptability and accessibility for ultrasound education for certain anatomical structures.
Comparison Canal Filling Ratio And Femoral Bone Density Change Between Wedge Taper And Anatomical Stem Design
Authors: ploynumpon Patcharavit , Chompoosang Thakrit
Published: November 2022

Purpose

comparative the outcome of proximal femoral bone density change in follow-up x-ray film and proximal filling ratio of stem between anatomical and double taper wedge cementless stem design

Methods

post-operative follow film of up to 1 year of patients who had undergone Total hip arthroplasty between 2552-2563, which is match inclusion criteria, was obtained from the radiology department. The measurement of Canal filling ratio (Lesser trochanter, 2 cm above LT and 7 cm below LT) and Femoral bone density change using optimal densitometry method to compare between Anatomical and double wedge taper stem type.

Result

92 patients,76% female, and 24% male, were match the inclusion criteria for this study. The mean age was 53.86±13.00 years old. The canal filling ratio in the double wedge taper group (Accolade II) was significantly higher than the anatomical stem group (ABGII) (p<0.001, p<0.001, p=0.013) in all levels of measurement. There were no significant differences between both types of the stem in femoral bone density change in zone 1,4. However. There were significant differences in femoral bone change, in which bone loss was higher in the anatomical stem group, in zone 7 (−25 VS −17, P= 0.010)

Conclusion

Double taper wedge stem design had a significantly higher canal filling ratio than the Anatomical stem at all levels and less femoral bone density loss in follow-up post-operative film at Zone 7. However, in zone 1,4, There was no significant difference in femoral bone density loss.
Cerebrovascular damage caused by the gut microbe/host co-metabolitep-cresol sulfate is prevented by blockade of the EGF receptor
Authors: Shah Sita N. , Knausenberger Tobias B-A. , Pontifex Matthew G. , Connell Emily , Le Gall Gwénaëlle , Hardy Tom A. J. , Randall David W. , McCafferty Kieran , Yaqoob Muhammad M. , Solito Egle , Müller Michael , Stachulski Andrew V. , Glen Robert C. , Vauzour David , Hoyles Lesley , McArthur Simon
Published: November 2022

Circulating levels of the gut microbe/host co-metabolite p-cresol sulfate (pCS) correlate with cerebrovascular event risk in individuals with chronic kidney disease, but whether this relationship is mechanistic is unclear. We hypothesised that pCS would impair function of the blood-brain barrier (BBB), the primary brain-vasculature interface. We report that pCS exposure impairs BBB integrity in human cellsin vitroand both acutely and chronically in mice, enhancing tracer extravasation, disrupting barrier-regulating tight junction components and ultimately affecting whole-brain transcriptomic activity.In vitroandin vivomechanistic studies showed that pCS activated epidermal growth factor receptor (EGFR) signalling, resulting in matrix metalloproteinase mobilisation and BBB damage. Furthermore, blockade of EGFR prevented the permeabilising effects of serum from haemodialysis patients upon cerebromicrovascular endotheliain vitro. Our results define a pathway linking the co- metabolite pCS with BBB damage and suggest targeting the EGFR may mitigate against cerebrovascular damage in CKD.
A Machine-Learning Approach for Predicting Depression Through Demographic and Socioeconomic Features
Authors: Sun Joseph , Liao Rory , Shalaginov Mikhail Y. , Zeng Tingying Helen
Published: November 2022

According to the World Health Organization, over 300 million people worldwide are affected by major depressive disorder (MDD) [1]. Individuals battling this mental condition may exhibit symptoms including anxiety, fatigue, and self-harm, all of which severely affect well-being and quality of life. Current trends in social media and population behavior bring up an urgent need for health professionals to strengthen mental health resources, improve access and accurately diagnose depression [2]. To mitigate the disparate impact of depression on people of different social and racial groups, this study identifies factors that strongly correlate with the prevalence of depression in U.S. adults using health data from the 2019 pre-pandemic National Health Institute Survey (NHIS) [3]. In this study we trained a random forest model capable of performing a classification task on American-adults survey data with an accuracy of 98.7%. Our results conclude that age, education, income, and household demographics are the primary factors impacting mental health. Awareness of these mental health stressors may motivate medical professionals, institutions, and governments to identify more effectively the at-risk people and alleviate their potential suffering from MDD. By receiving adequate mental health services, Americans can improve their quality of life and form a more fulfilling society.
Investigation into the Phenological Patterns of Trees in Socorro Plateau, Goa
Authors: Sathya C. , Murugash M.
Published: November 2022

Phenology is defined as the observation of biological events or life cycle phases that occur due to changes in climate and season. Primarily, phenology of all organisms is influenced by temperature fluctuations and quick climate changes which in turn regulate a variety of environmental factors. When discussing about the effects of climate change on ecosystems, phenology is especially important as many animals depend on the phenology of plants for their survival. Analysing the phenological patterns of a particular area can provide us with critical points on how ecosystems are affected by climate change. In this study, we have analysed the patterns of phenology for several trees and tried to identify any idiosyncrasies which may arise as a result of climate change and other similar factors. A total of 75 individuals belonging to 15 genera or 17 species were documented in Socorro plateau, Goa and their phenological patterns such as flowering, fruiting and leaf cover were recorded and analysed. The phenological patterns of the individual trees were compared in relation to each other such as in-between flowering and fruiting of the same species. In addition to this, the species were compared with each other in terms of their rate of flowering/fruiting to observe their inter-connected variations. Prospects for future research were identified to further promote studies in conservation biology of flora and fauna in the area and in climate change to mediate its effects.
Deep-learning based bioactive therapeutic peptides generation and screening
Authors: Zhang Haiping , Saravanan Konda Mani , Wei Yanjie , Jiao Yang , Yang Yang , Pan Yi , Wu Xuli , Zhang John Z.H.
Published: November 2022

Many bioactive peptides demonstrated therapeutic effects over-complicated diseases, such as antiviral, antibacterial, anticancer,etc. Similar to the generatingde novochemical compounds, with the accumulated bioactive peptides as a training set, it is possible to generate abundant potential bioactive peptides with deep learning. Such techniques would be significant for drug development since peptides are much easier and cheaper to synthesize than compounds. However, there are very few deep learning-based peptide generating models. Here, we have created an LSTM model (named LSTM_Pep) to generatede novopeptides and finetune learning to generatede novopeptides with certain potential therapeutic effects. Remarkably, the Antimicrobial Peptide Database has fully utilized in this work to generate various kinds of potential activede novopeptide. We proposed a pipeline for screening those generated peptides for a given target, and use Main protease of SARS-COV-2 as concept-of-proof example. Moreover, we have developed a deep learning-based protein-peptide prediction model (named DeepPep) for fast screening the generated peptides for the given targets. Together with the generating model, we have demonstrated iteratively finetune training, generating and screening peptides for higher predicted binding affinity peptides can be achieved. Our work sheds light on to the development of deep learning-based methods and pipelines to effectively generating and getting bioactive peptides with a specific therapeutic effect, and showcases how artificial intelligence can help discoverde novobioactive peptides that can bind to a particular target.
Prescription of anti-influenza drugs in Japan, 2014-2020: a retrospective study using open data from the national claims database
Authors: Sako Akahito , Gu Yoshiaki , Masui Yoshinori , Yoshimura Kensuke , Yanai Hidekatsu , Ohmagari Norio
Published: November 2022

Background

Both physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. We aimed to clarify the status of anti-influenza drug use by analyzing real-world data.

Methods

This retrospective study analyzed open data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers most claims data from national health insurance. We estimated the annual number of patients prescribed anti-influenza drugs, their age and sex distribution, drug costs, and regional disparities for the period 2014-2020.

Results

For 2014-2019, an estimated 6.7-13.4 million patients per year were prescribed anti-influenza drugs, with an annual cost of 22.3-48.0 billion JPY (Japanese Yen). In addition, 21.1-32.0 million rapid antigen tests were performed at a cost of 30.1-47.1 billion JPY. In 2017, laninamivir was the most frequently prescribed anti-influenza drug (48%), followed by oseltamivir (36%), while in 2018, the newly introduced baloxavir accounted for 40.8% of prescriptions. After the emergence of COVID-19, the number of patients prescribed anti-influenza drugs in 2020 dropped to just 14,000. In 2018, 37.6% of prescriptions were for patients aged < 20 years compared with 12.2% for those aged ≥ 65 years. Prescriptions for inpatients accounted for 1.1%, and the proportion of prescriptions for inpatients increased with age. Male were more likely than female to be prescribed anti-influenza drugs for inpatient.

Conclusions

Based on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs.
Seizure onset patterns predict outcome after stereotactic electroencephalography-guided laser amygdalohippocampotomy
Authors: Michalak Andrew J. , Greenblatt Adam , Wu Shasha , Tobochnik Steven , Dave Hina , Raghupathi Ramya , Esengul Yasar T. , Guerra Antonio , Tao James X. , Issa Naoum P. , Cosgrove Garth R. , Lega Bradley , Warnke Peter , Chen H. Isaac , Lucas Timothy , Sheth Sameer A. , Banks Garrett P. , Kwon Churl-Su , Feldstein Neil , Youngerman Brett , McKhann Guy , Davis Kathryn A. , Schevon Catherine
Published: November 2022

Objective

Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (sEEG) may miss seizure onset elsewhere. We hypothesized that sEEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the two-year outcomes of patients who underwent single-probe SLAH after sEEG and evaluated whether sEEG SOPs predict postoperative seizure freedom.

Methods

This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent sEEG followed by single probe SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. A SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was two-year Engel I classification or recurrent seizures before then, stratified by SOP category.

Results

58 patients were included with a mean follow-up duration of 39 ± 12 months after SLAH. Overall one-, two, and three-year Engel I seizure freedom probability was 54%, 36%, and 33% respectively. Patients with SOPs including low voltage fast activity or low frequency repetitive spiking had a 46% two-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log rank test, p = 0.00015).

Significance

Patients who underwent SLAH after sEEG had a low probability of seizure freedom at two years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Key Points

We described extended seizure outcomes in a five-center retrospective review of 58 patients.

Seizure onset patterns (SOP) were categorized as putative positive vs. negative predictors of postoperative seizure freedom.

Low voltage fast activity or low frequency repetitive spiking are associated with higher seizure freedom probability

A 0% Engel I probability was found for patients whose dominant SOP was rhythmic slowing or repetitive spiking in the theta or alpha frequency bands.
CRISPRi-Driven Osteogenesis in Adipose-Derived Stem Cells for Bone Healing and Tissue Engineering
Authors: Weston Jacob D. , Austin Brooke , Levis Hunter , Zitnay Jared , Weiss Jeffrey A. , Lawrence Brandon , Bowles Robby D.
Published: November 2022

Engineered bone tissue synthesized from mesenchymal stem cell progenitors has numerous applications throughout the fields of regenerative medicine and tissue engineering. However, these multipotent cells offer little tissue-building assistance without differentiation direction from environmental cues such as bone morphogenetic proteins (BMPs). Unfortunately, BMP dosing and environmental cues can be difficult to control bothin vitroand afterin vivodelivery. Several BMP antagonists are expressed by cells in response to BMP dosing that bind extracellular BMPs and reduce their effective concentration. Here, we use CRISPR-guided gene-modulation technology to downregulate the expression of three BMP antagonists, noggin, gremlin-1, and gremlin-2, in adipose-derived stem cells (ASCs). We show that regulating noggin using this method results in ASC osteogenesis without the need for exogenous growth factors. To demonstrate the versatility and the precision capabilities of these engineered cells, we employ them with CRISPRa multiplex-engineered chondrogenic cells as a proof-of-concept tissue engineering application by creating a tissue gradient similar to the fibrocartilage-to-mineralized-fibrocartilage gradient in the tendon/ligament enthesis or intervertebral disc attachment. In doing so, we show that multiple CRISPR multiplex engineered cell types can be utilized in concert to provide a high degree of tissue developmental control without the use of exogenous growth factors.
Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung
Authors: Kersten Kelly , You Ran , Liang Sophia , Tharp Kevin M. , Pollack Joshua , Weaver Valerie M. , Krummel Matthew F. , Headley Mark B.
Published: November 2022

The formation of a pre-metastatic niche is a critical step during the metastatic spread of cancer. One way by which primary tumors prime host cells at future metastatic sites is through local shedding of tumor-derived microparticles as a consequence of vascular sheer flow. However, it remains unclear how the uptake of such particles by resident immune cells affects their phenotype and function. Here we show that ingestion of tumor-derived microparticles by macrophages induces a rapid metabolic and phenotypic switch that is characterized by enhanced mitochondrial mass and function, increased oxidative phosphorylation and upregulation of cellular adhesion molecules resulting in reduced motility in the early metastatic lung. We show that this reprogramming event is dependent on signaling through the mTORC1, but not mTORC2 pathway, and is unique to uptake of tumor-derived microparticles. Together, these data support a mechanism by which uptake of tumor-derived microparticles induces reprogramming of macrophages to shape their fate and function in the early metastatic lung.