bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes After Revision Fixation With Cement Augmentation for Failed Intertrochanteric Fracture Fixation in Older Adult Patients
Authors: Huyke-Hernández Fernando A. , Only Arthur J. , Sorich Megan , Onizuka Naoko , Switzer Julie A. , Cunningham Brian P.
Published: October 2022

Introduction

Intertrochanteric (IT) fractures that fail fixation are traditionally treated with arthroplasty, introducing significant risk of morbidity and mortality in frail older adult patients. Revision fixation with cement augmentation is a relatively novel technique that has been reported in several small scale international studies. Here we report a clinical series of 22 patients that underwent revision fixation with cement augmentation for IT fracture fixation failure.

Methods

This retrospective case series identified all patients that underwent revision intramedullary nailing from 2018 to 2021 at two institutions within a large metropolitan healthcare system. Demographics, injury characteristics, Charlson Comorbidity Index score, and surgical characteristics were extracted from the electronic medical record. Outcomes were extracted from the electronic medical record and included radiographic findings, pain, functional outcomes, complications, and mortality.

Results

Average follow-up after revision surgery was 15.2 ± 10.6 months. Twenty patients (90.9%) reported improved pain and achieved union or progressive healing after surgery. Most of these patients regained some degree of independent ambulation (19 patients, 86.4%), with only 5 patients (22.7%) requiring increased assistance for their activities of daily living (ADLs). One-year mortality was 13.6% (3 patients). Of the 5 patients (22.7%) that experienced complications, 2 patients (9.1%) required revision hemiarthroplasty for subsequent fixation failure. The other 3 patients did well when complications resolved.

Conclusions

Revision fixation with cement augmentation can be an effective, safe, cost-effective alternative to arthroplasty for the management of cases involving non-infected failed IT fracture fixation with implant cut-out or cut-through limited to the femoral head in older adult patients that have appropriate acetabular bone stock.
International student education in China: An “Island” in Internationalization?
Authors: Wen Wen , Wang Lizhou , Cui Yanan
Published: October 2022

While many studies have studied Chinese international student experiences, including their motivations, choices, and socio-cultural adaptations, few have systematically analyzed the connection of international student education (ISE) to society. This paper incorporates the “internationalization in higher education for society” framework and the “glonacal agency heuristic” to examine ISE in China in relation to the goals of social justice, economic development, and public goods. The findings reveal dilemmas in institutional practices and instances of disconnection from local society, while also pointing to potential contributions to global society. The causes include instrumentalist values, competing policy priorities, and constrained institutional agency. China’s case offers practical implications for reconceptualizing ISE for other emerging student-receiving nations. Furthermore, this case may also contribute to growing scholarly discussions on integrating the internationalization of higher education into universities’ third mission of service to society across different countries. We argue that ISE should be designed and implemented comprehensively with intention and purpose, and undergirded by strengthened institutional agency directed to serve society.
Alcohol Binge Drinking–Induced ST-Segment-Elevation Acute Coronary Syndrome
Authors: Swarath Steven , Maharaj Nicole , Lalchansingh Dayna , Seecheran Rajeev , Seecheran Valmiki , Leyva Quert Abel Yoandri , Seecheran Naveen Anand
Published: October 2022

We present the case of a 26-year-old man, without any apparent cardiovascular risk factors, who experienced an ST-segment-elevation acute coronary syndrome after binge drinking high-proof alcohol, which was successfully managed with primary percutaneous coronary intervention and comprehensive, guideline-directed medical therapy.
Employee-Organization Identity Fusion: Connecting Leadership and Symmetrical Internal Communication to Identity- and Engagement-Related Outcomes
Authors: Krishna Arunima
Published: October 2022

Employees are key organizational stakeholders whose value to the enterprise’s functioning has long been emphasized in business communication literature. The present study serves to integrate business communication, organizational psychology, and leadership literature to advance a theoretically grounded model explaining employees’ job engagement. Drawing upon recent advances in consumer psychology and social identity scholarship on brand identity fusion, this study examines how employee-organization identity fusion, or a visceral feeling of oneness with the organization experienced by employees may contribute to their job engagement. Surveys conducted among employees belonging to corporations with one thousand or more employees revealed not only the power of authentic leadership and symmetrical communication in engendering employee-organization identity fusion, but also how leadership and communication can foster workers’ job engagement. The theoretical and managerial implications of this work are discussed (132 words).
A Key Driver of Patient Satisfaction: Interaction of Patients with Personnel Delivering Incontinence Health Technologies
Authors: Creazza Alessandro , Mastrosimone Erminia , Garagiola Elisabetta , Porazzi Emanuele
Published: October 2022

Primary care represents an answer to the growing demand of an ageing population for healthcare services outside the hospital. As a support mechanism of primary care, the distribution of health technologies to chronic patients plays an important role, but it has been investigated from the operational viewpoint only, ignoring the patient's perspective. We explored patient's satisfaction in relation to the distribution processes of incontinence health technologies, investigating its antecedents and isolating the factors driving the satisfaction of patients – which could be leveraged to design better distribution processes for better primary care services. We performed a survey study on 650 patients in primary care services affected by incontinence in Italy, building on the ServQual and Kano models. Partial Least Square Structural Equation Modelling (PLS-SEM) with Multi-Group Analysis (MGA) was adopted to analyse the data. Results show that interaction of patients with the personnel delivering the service is the key driver of patient satisfaction: this is an element more important than the operational features of distribution services (such as punctuality/reliability of the service or its flexibility).
Reply to the Letter to the Editor by Sipila, Jussi
Authors: James Lisa M , Georgopoulos Apostolos P
Published: October 2022

This a Reply to the Letter to the Editor by Sipila, Jussi regarding our article titled: James LM, Georgopoulos AP. High Correlations Among Worldwide Prevalences of Dementias, Parkinson’s Disease, Multiple Sclerosis, and Motor Neuron Diseases Indicate Common Causative Factors. Neurosci Insights. 2022 Aug 8;17:26331055221117598. doi: 10.1177/26331055221117598.
Facilitating and Implementing a Process for the Delivery of Pediatric Oncology New Diagnosis Education Among Nursing Staff Through the Electronic Medical Record
Authors: Collazo Christina K. , Tena Nancy , Duffy Elizabeth A.
Published: October 2022

Background: An estimated 11,060 children between the ages of 1 and 14 years and 4,900 adolescents between the ages of 15 and 19 years are diagnosed with cancer in the United States. Parents with children newly diagnosed with cancer must acquire new knowledge related to the diagnosis, treatment plan, psychosocial care, and home management therapies to safely provide care following discharge. Expert consensus and review of current evidence demonstrate that utilizing a new diagnosis education checklist allows the delivery of essential information to patients and caregivers. The checklist divides educational topics into three sections: primary, secondary, and tertiary topics. This project followed the completion of an evidence-based fellowship through Children's Oncology Group focusing upon the feasibility and efficacy of implementing a standardized new diagnosis education checklist. The fellowship identified secondary topic documentation and an electronic medical record (EMR) checklist as areas of future work. Methods: This quality improvement project focused upon nursing staffs’ documentation of secondary topics and the development/utilization of an EMR checklist. A pre–post survey design evaluated the outcomes of secondary topic documentation and EMR checklist implementation. Results: This nurse-led initiative created templates for primary and secondary topic checklists using Epic's SmartPhrase feature “.PHOPTED1” and “.PHOPTED2.” Secondary topic completion and documentation increased 26% following implementation, and over 40% of the nursing staff indicated that they were very likely to continue to use the new templates. Discussion: Project templates are readily applicable to institutions that utilize Epic. Template examples and strategies to facilitate inpatient/outpatient checklist completion are discussed.
Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma
Authors: Younes Anas , Burke John M. , Cheson Bruce D. , Diefenbach Catherine S. , Ferrari Silvia , Hahn Uwe H. , Hawkes Eliza A. , Khan Cyrus , Lossos Izidore S. , Musuraca Gerardo , Tani Monica , Vitolo Umberto , Yuen Sam , Raval Aparna , Shivhare Mahesh , Nielsen Tina G. , Sellam Gila , Sharman Jeff P.
Published: October 2022

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) and is curative in ∼60% of patients. Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets programmed death–ligand 1 and has previously shown antitumor activity in several tumor types. In a phase 1b/2 trial (NCT02596971), we evaluated the safety and efficacy of atezolizumab in combination with R-CHOP (atezo–R-CHOP; for 6-8 cycles) in patients with previously untreated DLBCL. Patients achieving a complete response (CR) at the end of induction received consolidation therapy with atezolizumab on day 1 of each 21-day cycle for an additional 17 cycles. Overall, 42 patients with DLBCL were included in this analysis. The primary endpoint, CR rate at the end of induction, as assessed by an independent review committee (modified Lugano 2014 criteria), was 77.5% (95% confidence interval [CI], 64.0-87.7; n = 40). Investigator-assessed progression-free survival and overall survival at 3 years were 77.4% (95% CI, 59.7-88.0) and 87.2% (95% CI, 71.9-94.5), respectively. All treated patients experienced ≥1 adverse event (AE; 32 patients [76.2%] had grade 3-4 AE). One patient had a fatal AE (unconfirmed progressive multifocal leukoencephalopathy) that was considered related to atezolizumab and rituximab, and 17 patients (40.5%) experienced atezolizumab-related AEs of special interest. In previously untreated patients with DLBCL, atezo–R-CHOP demonstrated encouraging clinical efficacy and a safety profile consistent with the known toxicities of the individual drugs. This trial was registered at www.clinicaltrials.gov as #NCT02596971.
Transporter-dependent uptake and metabolism of myocardial interstitial serotonin in the rat heart
Authors: Sonobe Takashi , Akiyama Tsuyoshi , Pearson James T.
Published: October 2022

To investigate the roles of the serotonin (5-HT) transporter (SERT) and plasma membrane monoamine transporter (PMAT) in 5-HT uptake and its metabolism in the heart, we monitored myocardial interstitial levels of 5-HT and 5-HIAA, a metabolite of 5-HT by monoamine oxidase (MAO), in anesthetized rats using a microdialysis technique. Fluoxetine (SERT inhibitor), decynium-22 (PMAT inhibitor), or their mixture was locally administered by reverse-microdialysis for 60 min. Subsequently, pargyline (MAO inhibitor) was co-administered. Fluoxetine rapidly increased dialysate 5-HT concentration, while decynium-22 gradually increased it. The mixture induced a larger increase in dialysate 5-HT concentration compared to fluoxetine or decynium-22 alone. Fluoxetine increased dialysate 5-HIAA concentration, and this increase was abolished by pargyline. Decynium-22 and the mixture did not change dialysate 5-HIAA concentration, which were not affected by pargyline. Both SERT and PMAT regulate myocardial interstitial 5-HT levels by its uptake; however, 5-HT uptake via PMAT leads to 5-HT metabolism by MAO.
Comparison of anther transcriptomes in response to cold stress at the reproductive stage between susceptible and resistant Japonica rice varieties
Authors: Guo Zhenhua , Ma Wendong , Cai Lijun , Guo Tao , Liu Hao , Wang Linan , Liu Junliang , Ma Bo , Feng Yanjiang , Liu Chuanxue , Pan Guojun
Published: October 2022

Background

Rice is one of the most important cereal crops in the world but is susceptible to cold stress (CS). In this study, we carried out parallel transcriptomic analysis at the reproductive stage on the anthers of two Japonica rice varieties with contrasting CS resistance: cold susceptible Longjing11 (LJ11) and cold resistant Longjing25 (LJ25).

Results

According to the obtained results, a total of 16,762 differentially expressed genes (DEGs) were identified under CS, including 7,050 and 14,531 DEGs in LJ25 and LJ11, respectively. Examining gene ontology (GO) enrichment identified 35 up- and 39 down-regulated biological process BP GO terms were significantly enriched in the two varieties, with ‘response to heat’ and ‘response to cold’ being the most enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 33 significantly enriched pathways. Only the carbon metabolism and amino acid biosynthesis pathways with down-regulated DEGs were enriched considerably in LJ11, while the plant hormone signal transduction pathway (containing 153 DEGs) was dramatically improved. Eight kinds of plant hormones were detected in the pathway, while auxin, abscisic acid (ABA), salicylic acid (SA), and ethylene (ETH) signaling pathways were found to be the top four pathways with the most DEGs. Furthermore, the protein-protein interaction (PPI) network analysis identified ten hub genes (co-expressed gene number ≥ 30), including six ABA-related genes. Various DEGs (such as OsDREB1A, OsICE1, OsMYB2, OsABF1, OsbZIP23, OsCATC, and so on) revealed distinct expression patterns among rice types when the DEGs between LJ11 and LJ25 were compared, indicating that they are likely responsible for CS resistance of rice in cold region.

Conclusion

Collectively, our findings provide comprehensive insights into complex molecular mechanisms of CS response and can aid in CS resistant molecular breeding of rice in cold regions.
De novo transcriptome profiling unveils the regulation of phenylpropanoid biosynthesis in unripe Piper nigrum berries
Authors: Sreekumar Sweda , Divya Kattupalli , Joy Nisha , Soniya E. V.
Published: October 2022

Background

Black pepper (Piper nigrum L.) is rich in bioactive compounds that make it an imperative constituent in traditional medicines. Although the unripe fruits have long been used in different Ayurvedic formulations, the mechanism of gene regulation resulting in the production of the bioactive compounds in black pepper is not much investigated. Exploring the regulatory factors favouring the production of bioactive compounds ultimately help to accumulate the medicinally important content of black pepper. The factors that enhance the biosynthesis of these compounds could be potential candidates for metabolic engineering strategies to obtain a high level production of significant biomolecules.

Results

Being a non-model plant, de novo sequencing technology was used to unravel comprehensive information about the genes and transcription factors that are expressed in mature unripe green berries of P. nigrum from which commercially available black pepper is prepared. In this study, the key gene regulations involved in the synthesis of bioactive principles in black pepper was brought out with a focus on the highly expressed phenylpropanoid pathway genes. Quantitative real-time PCR analysis of critical genes and transcription factors in the different developmental stages from bud to the mature green berries provides important information useful for choosing the developmental stage that would be best for the production of a particular bioactive compound. Comparison with a previous study has also been included to understand the relative position of the results obtained from this study.

Conclusions

The current study uncovered significant information regarding the gene expression and regulation responsible for the bioactivity of black pepper. The key transcription factors and enzymes analyzed in this study are promising targets for achieving a high level production of significant biomolecules through metabolic engineering.
How can clinicians choose between conflicting and discordant systematic reviews? A replication study of the Jadad algorithm
Authors: Lunny C , Thirugnanasampanthar Sai Surabi , Kanji S , Ferri N , Pieper D , Whitelaw S , Tasnim S , Nelson H , Reid EK , Zhang Jia He , Kalkat Banveer , Chi Yuan , Abdoulrezzak Reema , Zheng Di Wen , Pangka Lindy R.S. , Wang Dian , Safavi Parisa , Sooch Anmol , Kang Kevin T. , Tricco Andrea C,
Published: October 2022

Introduction

The exponential growth of published systematic reviews (SRs) presents challenges for decision makers seeking to answer clinical, public health or policy questions. In 1997, an algorithm was created by Jadad et al. to choose the best SR across multiple. Our study aims to replicate author assessments using the Jadad algorithm to determine: (i) if we chose the same SR as the authors; and (ii) if we reach the same results.

Methods

We searched MEDLINE, Epistemonikos, and Cochrane Database of SRs. We included any study using the Jadad algorithm. We used consensus building strategies to operationalise the algorithm and to ensure a consistent approach to interpretation.

Results

We identified 21 studies that used the Jadad algorithm to choose one or more SRs. In 62% (13/21) of cases, we were unable to replicate the Jadad assessment and ultimately chose a different SR than the authors. Overall, 18 out of the 21 (86%) independent Jadad assessments agreed in direction of the findings despite 13 having chosen a different SR.

Conclusions

Our results suggest that the Jadad algorithm is not reproducible between users as there are no prescriptive instructions about how to operationalise the algorithm. In the absence of a validated algorithm, we recommend that healthcare providers, policy makers, patients and researchers address conflicts between review findings by choosing the SR(s) with meta-analysis of RCTs that most closely resemble their clinical, public health, or policy question, are the most recent, comprehensive (i.e. number of included RCTs), and at the lowest risk of bias.
Prescription characteristics associated with fall-related injury risk among older adults prescribed benzodiazepines: a cohort study
Authors: Maust Donovan T. , Bohnert Amy S. B. , Strominger Julie , Alexander Neil , Min Lillian , Hoffman Geoffrey J. , Goldstick Jason E.
Published: October 2022

Background

Benzodiazepines (BZD) are widely prescribed to older adults despite their association with increased fall injury. Our aim is to better characterize risk-elevating factors among those prescribed BZD.

Methods

A retrospective cohort study using a 20% sample of﻿ Medicare beneficiaries with Part D prescription drug coverage. Patients with a BZD prescription (“index”) between 1 April 2016 and 31 December 2017 contributed to incident (n=379,273) and continuing (n=509,634) cohorts based on prescriptions during a 6-month pre-index baseline. Exposures were index BZD average daily dose and days prescribed; baseline BZD medication possession ratio (MPR) (for the continuing cohort); and co-prescribed central nervous system-active medications. Outcome was a treated fall-related injury within 30 days post-index BZD, examined using Cox proportional hazards adjusting for demographic and clinical covariates and the dose prescribed.

Results

Among incident and continuing cohorts, 0.9% and 0.7% experienced fall injury within 30 days of index. In both cohorts, injury risk was elevated immediately post-index among those prescribed the lowest quantity: e.g., for <14-day fill (ref: 14-30 days) in the incident cohort, risk was 37% higher the 10 days post-fill (adjusted hazard ratio [HR] 1.37 [95% confidence interval [CI] 1.19-1.59]). Risk was elevated immediately post-index for continuing users with low baseline BZD exposure (e.g., for MPR <0.5 [ref: MPR 0.5-1], HR during days 1-10 was 1.23 [CI 1.08-1.39]). Concurrent antipsychotics and opioids were associated with elevated injury risk in both cohorts (e.g., incident HRs 1.21 [CI 1.03-1.40] and 1.22 [CI 1.07-1.40], respectively; continuing HRs 1.23 [1.10-1.37] and 1.21 [1.11-1.33]).

Conclusions

Low baseline BZD exposure and a small index prescription were associated with higher fall injury risk immediately after a BZD fill. Concurrent exposure to antipsychotics and opioids were associated with elevated short-term risk for both incident and continuing cohorts.
Tuberculosis treatment adherence in the era of COVID-19
Authors: Lippincott Christopher K. , Perry Allison , Munk Elizabeth , Maltas Gina , Shah Maunank
Published: October 2022

Background

In-person directly observed therapy (DOT) is commonly used for tuberculosis (TB) treatment monitoring in the US, with increasing usage of video-DOT (vDOT). We evaluated the impact of COVID-19 on TB treatment adherence, and utilization and effectiveness of vDOT.

Methods

We abstracted routinely collected data on individuals treated for TB disease in Baltimore, Maryland between April 2019 and April 2021. Our primary outcomes were to assess vDOT utilization and treatment adherence, defined as the proportion of prescribed doses (7 days/week) verified by observation (in-person versus video-DOT), comparing individuals in the pre-COVID and COVID (April 2020) periods.

Results

Among 52 individuals with TB disease, 24 (46%) received treatment during the COVID-19 pandemic. vDOT utilization significantly increased in the COVID period (18/24[75%]) compared to pre-COVID (12/28[43%], p = 0.02). Overall, median verified adherence was similar pre-COVID and COVID periods (65% versus 68%, respectively, p = 0.96). Adherence was significantly higher overall when using vDOT (median 86% [IQR 70–98%]) compared to DOT (median 59% [IQR 55-64%], p < 0.01); this improved adherence with vDOT was evident in both the pre-COVID (median 98% vs. 58%, p < 0.01) and COVID period (median 80% vs. 62%, p = 0.01).

Conclusion

vDOT utilization increased during the COVID period and was more effective than in-person DOT at verifying ingestion of prescribed treatment.
Conservative therapy is associated with worse clinical features and biochemical derangements than renal replacement therapy: a retrospective study in Kumasi, Ghana
Authors: Okyere Perditer , Okyere Isaac , Essuman Grace , Attakora Joseph , Serwaa Dorcas , Donkoh Irene Esi , Ephraim Richard K.D.
Published: October 2022

Background

The incidence of end stage kidney disease (ESKD) is increasing in Ghana as with the rest of the world. This study compared the sociodemographic, diagnostic characteristics (clinical, biochemical and imaging) and clinical outcomes of ESKD patients who chose either renal replacement therapy (RRT) or conservative therapy as well as the factors that influenced their choice.

Methods

We retrospectively reviewed the records of 382 ESKD patient from 2006 to 2018. The data was collected from the Nephrology Clinic at the Komfo Anokye Teaching Hospital (KATH). Sociodemographic, diagnostic (clinical, biochemical and imaging) and therapeutic data were obtained, organized and analyzed with Statistical Package for the Social Sciences (SPSS).

Results

Of the 382 patients, 321 had conservative therapy whiles 61 had renal replacement therapy. The mean age of participants was 47.71 ± 16.10 years. Bipedal swelling (16.8%), fatigue (10.4%) and facial swelling (9.2%) were the major clinical features. Chronic glomerulonephritis (31.4%), hypertension (30.3%) and diabetes mellitus nephropathy (28.2%) were the most frequent predisposing conditions. Nifedipine (82.0%), bisoprolol (32.8%), aspirin (19.7%), ranitidine (26.2%), metformin (13.1%) and lasix (78.7%) were commonly used by the RRT patients than their conservative therapy counterparts. Compared to their RRT counterparts, patients on conservative therapy were more on irbesartan/lisinopril (57.9%) and sodium hydro carbonate (NaHCO3) (52.0%). Diastolic blood pressure (DBP) (p = 0.047), uremic gastritis (p = 0.007), anaemia, uraemia, haematuria and hyperkalaemia (p < 0.001) were more common in conservative therapy patients than RRT patients with RRT patients showing better corticomedullary differentiation (38.1% vs. 27.7%, p < 0.001) and normal echotexture (15.0% vs. 11.6%, p = 0.005). Age, gender, occupation and duration of illness were significantly associated with the decision to opt for conservative therapy.

Conclusion

Patients on conservative therapy have worse clinical outcomes than their RRT counterparts. Early referrals to nephrologist as well as subsidized RRT should be targeted.
Respectful maternity care in health centers of Addis Ababa city: a mixed method study
Authors: Abebe Amaha Haile , Mmusi-Phetoe Rose
Published: October 2022

Objective

The study aims to assess quality of obstetric and newborn care including respectfulness of the maternity care.

Design

The study used explanatory sequential mixed methods design .

Setting

This study was conducted in 50 health centres in Addis Ababa city administration January 25 to April 31, 2021.

Methods

During the quantitative phase 500 women in postpartum period were interviewed using structured questionnaire. In the second phase in-depth interview was conducted with 20 midwives and 13 health centre managers. The quantitative data was analysed using Statistical Package for Social Sciences (SPSS). The qualitative data was analysed using Colaizzi’s seven step process.

Results

Only 24.6% of women had respectful maternity care (RMC). Only 46% of women had effective communication during child birth. Only 9.6% of women had emotional support during child birth. Majority of women were encouraged to mobilize, take food and be on labor position of their choice. However, only 22.4 and 18.8% of women respectively had a companion of choice and any pharmacologic pain relief during child birth. One in seven women (15%) had one form of disrespect and abuse during child birth.

Conclusion

Ensuring respectful maternity care needs strong policy direction to health facilities, public education on their right to respectful maternity care, training of care givers and monitoring care through engagement of frontline staff and clients.
Feasibility of fractionated gamma knife radiosurgery in the management of newly diagnosed Glioblastoma
Authors: Gallitto Matthew , Savacool Michelle , Lee Albert , Wang Tony J. C. , Sisti Michael B.
Published: October 2022

Background

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with overall survival remaining poor despite ongoing efforts to explore new treatment paradigms. Given these outcomes, efforts have been made to shorten treatment time. Recent data report on the safety of CyberKnife (CK) fractionated stereotactic radiosurgery (SRS) in the management of GBM using a five-fraction regimen. The latest Gamma Knife (GK) model also supports frameless SRS, and outcomes using GK SRS in the management of primary GBM have not yet been reported.

Objective

To report on the feasibility of five-fraction SRS with the GammaKnife ICON in the management of newly diagnosed GBM.

Methods

In this single institutional study, we retrospectively reviewed all patients from our medical center from January 2017 through December 2021 who received fractionated SRS with Gamma Knife ICON for newly diagnosed GBM. Patient demographics, upfront surgical margins, molecular subtyping, radiation treatment volumes, systemic therapies, and follow-up imaging findings were extracted to report on oncologic outcomes.

Results

We identified six patients treated within the above time frame. Median age at diagnosis was 73.5 years, 66% were male, and had a median Karnofsky Performance Status (KPS) of 70. All tumors were IDH wild-type, and all but one were MGMT methylated and received concurrent temozolomide (TMZ). Within this group, progression free survival was comparable to that of historical data without significant radiation-induced toxicities.

Conclusion

Gamma Knife ICON may be discussed as a potential treatment option for select GBM patients and warrants further investigation in the prospective setting.
A potential pathogenic hypoxia-related gene HK2 in necrotizing enterocolitis (NEC) of newborns
Authors: Han Yujie , Liu Xianghong , Kang Lili , Chen Dong , Li Yongqing , Zhang Huiping , Sun Mingying , Gao Hui , Gai Zhongtao , Li Xiaoying
Published: October 2022

Background

Necrotizing enterocolitis (NEC) is a disastrous gastrointestinal disease of newborns, and the mortality rate of infants with NEC is approximately 20%-30%. The exploration of pathogenic targets of NEC will be conducive to timely diagnosis of NEC.

Methods

The whole transcriptome RNA sequencing was performed on NEC samples to reveal the expression of lncRNAs, circRNAs, miRNAs and mRNAs. Using differential expression analysis, cross analysis, target prediction, enrichment analysis, the pathogenic ceRNA network and target was found.

Results

Preliminarily, 281 DEmRNAs, 21 DEmiRNAs, 253 DElncRNAs and 207 DEcircRNAs were identified in NEC samples compared with controls. After target prediction and cross analyses, a key ceRNA regulatory network was built including 2 lncRNAs, 4 circRNAs, 2 miRNAs and 20 mRNAs. These 20 mRNAs were significantly enriched in many carbohydrate metabolism related pathways. After cross analysis of hypoxia-, carbohydrate metabolism-related genes, and 20 core genes, one gene HK2 was finally obtained. Dendritic cells activated were significantly differentially infiltrated and negatively correlated with HK2 expression in NEC samples.

Conclusions

The promising pathogenic hypoxia-related gene HK2 has been firstly identified in NEC, which might also involve in the carbohydrate metabolism in NEC.
Technical feasibility of using auditory phase-targeted stimulation after pediatric severe traumatic brain injury in an intensive care setting
Authors: Albrecht Joëlle Ninon , Jaramillo Valeria , Huber Reto , Karlen Walter , Baumann Christian Rainer , Brotschi Barbara
Published: October 2022

Background

Supplementary treatment options after pediatric severe traumatic brain injury (TBI) are needed to improve neurodevelopmental outcome. Evidence suggests enhancement of brain delta waves via auditory phase-targeted stimulation might support neuronal reorganization, however, this method has never been applied in analgosedated patients on the pediatric intensive care unit (PICU). Therefore, we conducted a feasibility study to investigate this approach: In a first recording phase, we examined feasibility of recording over time and in a second stimulation phase, we applied stimulation to address tolerability and efficacy.

Methods

Pediatric patients (> 12 months of age) with severe TBI were included between May 2019 and August 2021. An electroencephalography (EEG) device capable of automatic delta wave detection and sound delivery through headphones was used to record brain activity and for stimulation (MHSL-SleepBand version 2). Stimulation tolerability was evaluated based on report of nurses, visual inspection of EEG data and clinical signals (heart rate, intracranial pressure), and whether escalation of therapy to reduce intracranial pressure was needed. Stimulation efficacy was investigated by comparing EEG power spectra of active stimulation versus muted stimulation (unpaired t-tests).

Results

In total, 4 out of 32 TBI patients admitted to the PICU (12.5%) between 4 and 15 years of age were enrolled in the study. All patients were enrolled in the recording phase and the last one also to the stimulation phase. Recordings started within 5 days after insult and lasted for 1–4 days. Overall, 23–88 h of EEG data per patient were collected. In patient 4, stimulation was enabled for 50 min: No signs of patient stress reactions were observed. Power spectrums between active and muted stimulation were not statistically different (all P > .05).

Conclusion

Results suggests good feasibility of continuously applying devices needed for auditory stimulation over multiple days in pediatric patients with TBI on PICU. Very preliminary evidence suggests good tolerability of auditory stimuli, but efficacy of auditory stimuli to enhance delta waves remains unclear and requires further investigation. However, only low numbers of severe TBI patients could be enrolled in the study and, thus, future studies should consider an international multicentre approach.
COVID-19 vaccination coverage among patients with psychiatric disorders in China during the pandemic: a cross-sectional study
Authors: Qin Yue , Zhao Ziru , Teng Ziwei , Xu Baoyan , Wang Xianghe , Guo Jingyi , Huang Jing , Wu Haishan
Published: October 2022

Background:

To investigate the Coronavirus Disease 2019 (COVID-19) vaccination coverage and the influential factors of vaccination among patients with mental disorders, we conducted a cross-sectional study in China.

Method:

The anonymous questionnaires including demographic data, vaccination status, intention to be vaccinated and its reasons were collected in the Second Xiangya Hospital, one of the biggest four psychiatric centers in China. Mental health of these participants were measured by the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder-7 items (GAD-7). The influential factors associated with vaccination status were analyzed by Fisher exact tests and binary logistical analysis.

Result:

1328 patients and 922 family members completed the survey. The vaccination rate of patients included was 69.4%, whereas 85.5% patients were willing to be vaccinated. Being hospitalized (aOR 0.41, 95% CI:0.27–0.60), suffering from schizophrenia (aOR 0.38, 95% CI: 0.19–0.75) and secondary school educational background (aOR 0.58, 95% CI: 0.37–0.93) were significantly associated with less likelihood to get vaccinated. Uptaking vaccines could reduce depressive (aOR 0.63, 95% CI: 0.41–0.98) or anxious symptoms (aOR 0.40, 95% CI: 0.25–0.63) in these patients for a short period.

Conclusion:

Further COVID-19 immunization programme should prioritize hospitalized psychiatric patients and schizophrenic patients since their demands for vaccination had been partly ignored during the current inoculation.
Screening and brief intervention for alcohol use disorder risk in three middle-income countries
Authors: Paschall Mallie J. , Ringwalt Christopher L. , Fisher Deborah A. , Grube Joel W. , Achoki Tom , Miller Ted R.
Published: October 2022

Background

This study examined the prevalence of screening and brief intervention (SBI) for alcohol use disorder (AUD) risk in samples of adult drinkers in three middle-income countries (Brazil, China, South Africa), and the extent to which meeting criteria for AUD risk was associated with SBI.

Methods

Cross-sectional survey data were collected from adult samples in two cities in each country in 2018. Survey measures included past-year alcohol use, the CAGE assessment for AUD risk, talking to a health care professional in the past year, alcohol use screening by a health care professional, receiving advice about drinking from a health care professional, and sociodemographic characteristics. The prevalence of SBI was determined for past-year drinkers in each country and for drinkers who had talked to a health care professional. Logistic regression analyses were conducted to examine whether meeting criteria for AUD risk was associated with SBI when adjusting for sociodemographic characteristics.

Results

Among drinkers at risk for AUD, alcohol use screening rates ranged from 6.7% in South Africa to 14.3% in Brazil, and brief intervention rates ranged from 4.6% in South Africa to 8.2% in China. SBI rates were higher among drinkers who talked to a health care professional in the past year. In regression analyses, AUD risk was positively associated with SBI in China and South Africa, and with brief intervention in Brazil.

Conclusion

Although the prevalence of SBI among drinkers at risk for AUD in Brazil, China, and South Africa appears to be low, it is encouraging that these drinkers were more likely to receive SBI.
Impacts of food consumption on biochemical markers and anthropometric variables of women with metabolic syndrome
Authors: Michalichen Kelly Cristiane , Weber Vinícius Muller Reis , Queiroga Marcos Roberto , Fernandes Daniel Zanardini , Carreira Clisia Mara , Vieira Edgar Ramos , Venturini Danielle
Published: October 2022

Background

Metabolic syndrome (MetS) is a group of diseases characterized by insulin resistance. MetS has high prevalence among women, which is impacted by food intake. MetS is related to high level of inflammation; however, the impacts of whole diets on biochemical and anthropometrical markers and the effects on MetS need to be further elucidated. In this case, the objective of this study was to assess the relationship between food intake, biochemical and anthropometrical markers in women with MetS.

Methods

This is a cross-sectional study, in which 1 hundred and 22 women participated in the assessment of biochemical (glycated hemoglobin, glycaemia, insulin, uric acid, total cholesterol, HDL-c, LDL-c, triglycerides, C-reactive protein) and anthropometrical (body mass, height, waist circumference - WC) variables. Participants also performed blood pressure and 24-hour dietary recall assessments. Out of the 122 participants, 44 (36%, age: 59 ± 11 years) had MetS and were included in the analysis.

Results

The consumption of monounsaturated fats had direct relationship with glycaemia (b = 7.48), whereas the consumption of fibers had inverse relationship with body mass (b = − 0.71) and WC (b = − 0.56).

Conclusion

The intake of monounsaturated fats and fiber was related to higher blood sugar levels and lower body mass and WC, respectively. These relationships elucidate and highlight the significance and importance of adequate diet in women with MetS.
Neutrophil degranulation and severely impaired extracellular trap formation at the basis of susceptibility to infections of hemodialysis patients
Authors: Talal Salti , Mona Khoury , Karem Awad , Yaniv Lerenthal , Reut Harari-Misgav , Ariel Shemesh , Moran Avraham-Kelbert , Harel Eitam , Campisi-Pinto Salvatore , Mahmoud Abu-Amna , Raul Colodner , David Tovbin , Gil Bar-Sela , Idan Cohen
Published: October 2022

Background

Chronic kidney disease patients are at increased risk of mortality with cardiovascular diseases and infections as the two leading causes of death for end-stage kidney disease treated with hemodialysis (HD). Mortality from bacterial infections in HD patients is estimated to be 100–1000 times higher than in the healthy population.

Methods

We comprehensively characterized highly pure circulating neutrophils from HD and healthy donors.

Results

Protein levels and transcriptome of HD patients’ neutrophils indicated massive neutrophil degranulation with a dramatic reduction in reactive oxygen species (ROS) production during an oxidative burst and defective oxidative cellular signaling. Moreover, HD neutrophils exhibit severely impaired ability to generate extracellular NET formation (NETosis) in NADPH oxidase-dependent or independent pathways, reflecting their loss of capacity to kill extracellular bacteria. Ectopic hydrogen peroxidase (H2O2) or recombinant human SOD-1 (rSOD-1) partly restores and improves the extent of HD dysfunctional neutrophil NET formation.

Conclusions

Our report is one of the first singular examples of severe and chronic impairment of NET formation leading to substantial clinical susceptibility to bacteremia that most likely results from the metabolic and environmental milieu typical to HD patients and not by common human genetic deficiencies. In this manner, aberrant gene expression and differential exocytosis of distinct granule populations could reflect the chronic defect in neutrophil functionality and their diminished ability to induce NETosis. Therefore, our findings suggest that targeting NETosis in HD patients may reduce infections, minimize their severity, and decrease the mortality rate from infections in this patient population.
Several areas of overlap between obesity and aging indicate obesity as a biomarker of accelerated aging of human B cell function and antibody responses
Authors: Frasca Daniela
Published: October 2022

Aging and obesity are high risk factors for several conditions and diseases. They are both associated with systemic inflammation and they are both ameliorated by a healthy life style, suggesting that they may share cellular and molecular pathways and underlying mechanisms. A close relationship between aging and obesity is also supported by the observation that the aging overweight/obese population is increasing worldwide, and mechanisms involved will be presented here. A focus of our work is to evaluate if obesity may be considered a good biomarker of accelerated aging of human antibody responses. We will summarize our published results showing the effects of obesity in accelerating age defects in the peripheral B cell pool and how these lead to dysfunctional humoral immunity.
Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial
Authors: Cortes Jorge E. , Lin Tara L. , Asubonteng Kobby , Faderl Stefan , Lancet Jeffrey E. , Prebet Thomas
Published: October 2022

CPX-351 (Europe: Vyxeos® liposomal; United States: Vyxeos®) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 improved the remission frequency, overall survival, and post-transplant survival versus 7 + 3. This post hoc analysis evaluated the final 5-year follow-up outcomes according to the European LeukemiaNet 2017 risk classification. CPX-351–treated patients had a higher remission frequency (adverse risk: 41% vs 26%; intermediate risk: 58% vs 39%) and longer median overall survival (adverse risk: 7.59 vs 5.52 months; intermediate risk: 11.86 vs 7.75 months) and post-transplant survival (adverse risk: 43.14 vs 7.08 months; intermediate risk: not reached vs 13.57 months) versus 7 + 3, with outcomes generally poorer among patients with adverse-risk AML. The safety profile of CPX-351 among patients with adverse-risk or intermediate-risk AML was consistent with that of the overall study population. Early mortality was lower, and hospitalization length of stay per patient-year was shorter with CPX-351 versus 7 + 3 within the adverse-risk and intermediate-risk subgroups. The favorable outcomes observed with CPX-351 in this post hoc analysis are consistent with results for the overall study population and further support the use of CPX-351 in these patients.

ClinicalTrials.gov Identifier: NCT01696084.
LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer
Authors: Cave Donatella Delle , Buonaiuto Silvia , Sainz Bruno , Fantuz Marco , Mangini Maria , Carrer Alessandro , Di Domenico Annalisa , Iavazzo Tea Teresa , Andolfi Gennaro , Cortina Carme , Sevillano Marta , Heeschen Christopher , Colonna Vincenza , Corona Marco , Cucciardi Antonio , Di Guida Martina , Batlle Eduard , De Luca Annachiara , Lonardo Enza
Published: October 2022

Background

Tumor-initiating cells (TIC), also known as cancer stem cells, are considered a specific subpopulation of cells necessary for cancer initiation and metastasis; however, the mechanisms by which they acquire metastatic traits are not well understood.

Methods

LAMC2 transcriptional levels were evaluated using publicly available transcriptome data sets, and LAMC2 immunohistochemistry was performed using a tissue microarray composed of PDAC and normal pancreas tissues. Silencing and tracing of LAMC2 was performed using lentiviral shRNA constructs and CRISPR/Cas9-mediated homologous recombination, respectively. The contribution of LAMC2 to PDAC tumorigenicity was explored in vitro by tumor cell invasion, migration, sphere-forming and organoids assays, and in vivo by tumor growth and metastatic assays. mRNA sequencing was performed to identify key cellular pathways upregulated in LAMC2 expressing cells. Metastatic spreading induced by LAMC2- expressing cells was blocked by pharmacological inhibition of transforming growth factor beta (TGF-β) signaling.

Results

We report a LAMC2-expressing cell population, which is endowed with enhanced self-renewal capacity, and is sufficient for tumor initiation and differentiation, and drives metastasis. mRNA profiling of these cells indicates a prominent squamous signature, and differentially activated pathways critical for tumor growth and metastasis, including deregulation of the TGF-β signaling pathway. Treatment with Vactosertib, a new small molecule inhibitor of the TGF-β type I receptor (activin receptor-like kinase-5, ALK5), completely abrogated lung metastasis, primarily originating from LAMC2-expressing cells.

Conclusions

We have identified a highly metastatic subpopulation of TICs marked by LAMC2. Strategies aimed at targeting the LAMC2 population may be effective in reducing tumor aggressiveness in PDAC patients. Our results prompt further study of this TIC population in pancreatic cancer and exploration as a potential therapeutic target and/or biomarker.
Microalgal photoautotrophic growth induces pH decrease in the aquatic environment by acidic metabolites secretion
Authors: Wu Mingcan , Wu Guimei , Lu Feimiao , Wang Hongxia , Lei Anping , Wang Jiangxin
Published: October 2022

Background

Microalgae can absorb CO2 during photosynthesis, which causes the aquatic environmental pH to rise. However, the pH is reduced when microalga Euglena gracilis (EG) is cultivated under photoautotrophic conditions. The mechanism behind this unique phenomenon is not yet elucidated.

Results

The present study evaluated the growth of EG, compared to Chlorella vulgaris (CV), as the control group; analyzed the dissolved organic matter (DOM) in the aquatic environment; finally revealed the mechanism of the decrease in the aquatic environmental pH via comparative metabolomics analysis. Although the CV cell density was 28.3-fold that of EG, the secreted-DOM content from EG cell was 49.8-fold that of CV (p-value < 0.001). The main component of EG’s DOM was rich in humic acids, which contained more DOM composed of chemical bonds such as N–H, O–H, C–H, C=O, C–O–C, and C–OH than that of CV. Essentially, the 24 candidate biomarkers metabolites secreted by EG into the aquatic environment were acidic substances, mainly lipids and lipid-like molecules, organoheterocyclic compounds, organic acids, and derivatives. Moreover, six potential critical secreted-metabolic pathways were identified.

Conclusions

This study demonstrated that EG secreted acidic metabolites, resulting in decreased aquatic environmental pH. This study provides novel insights into a new understanding of the ecological niche of EG and the rule of pH change in the microalgae aquatic environment.