bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities and challenges of global health diplomacy for prevention and control of noncommunicable diseases: a systematic review
Authors: Asadi-Lari Mohsen , Ahmadi Teymourlouy Ahmad , Maleki Mohammadreza , Afshari Mahnaz
Published: November 2021

Background and aim

The growing globalization has changed the goals and methods of diplomacy. Due to the challenges and complexities of dealing with noncommunicable diseases (NCDs) at the national and international levels, policy makers require global health diplomacy (GHD) to achieve the goals of prevention and control of NCDs. The purpose of this systematic review was to identify the challenges and opportunities in GHD for NCDs.

Methods

A systematic review of articles was conducted by searching MEDLINE via PubMed, Web of Science, Scopus, and Embase and by using Google and Google Scholar search engines. Additional articles were identified by reviewing reference lists and a number of special journals. The inclusion criteria include literature published in English from 2007 to 2020, and the exclusion criteria are literature published in any language other than English, absence of full text, dissertations, and duplicates. Overall, 32 articles met the requirements for inclusion in this review and were analyzed using content analysis in MAXQDA 10.

Findings

There are 32 published articles on GHD for NCDs. Identified challenges were classified into three levels: global (global health governance), national (Governance at the state level, health sector, and civil society), and industry. The progress on global health issues has created opportunities for the development of GHD for the prevention and control of NCDs. These opportunities were divided into three levels: international, national, and individual level.

Conclusion

Various challenges at the global level, national level, and industry led to less engagement of policymakers in GHD for prevention and control of NCDs and, as a consequence, a less coordinated approach to address prevention and control of NCDs worldwide. So, there is a need for more efforts of collective action and negotiation for tackling NCDs. Policymakers and managers of the health system should increase the advocacy, building a coalition with civil society, use negotiation and diplomacy to engage with other sectors and organizations, manage industry conflicts, and leverage foreign policy to promote health and welfare.
BDdb: a comprehensive platform for exploration and utilization of birth defect multi-omics data
Authors: Zhang Dengwei , Zhou Si , Zhou Ziheng , Jiang Xiaosen , Chen Dongsheng , Sun Hai-Xi , Huang Jie , Qu Shoufang , Yang Songchen , Gu Ying , Zhang Xiuqing , Jin Xin , Gao Ya , Shen Yue , Chen Fang
Published: November 2021

Background

Birth defects pose a major challenge to infant health. Thus far, however, the causes of most birth defects remain cryptic. Over the past few decades, considerable effort has been expended on disclosing the underlying mechanisms related to birth defects, yielding myriad treatises and data. To meet the increasing requirements for data resources, we developed a freely accessible birth defect multi-omics database (BDdb, http://t21omics.cngb.org) consisting of multi-omics data and potential disease biomarkers.

Results

In total, omics datasets from 136 Gene Expression Omnibus (GEO) Series records, including 5245 samples, as well as 869 biomarkers of 22 birth defects in six different species, were integrated into the BDdb. The database provides a user-friendly interface for searching, browsing, and downloading data of interest. The BDdb also enables users to explore the correlations among different sequencing methods, such as chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) from different studies, to obtain the information on gene expression patterns from diverse aspects.

Conclusion

To the best of our knowledge, the BDdb is the first comprehensive database associated with birth defects, which should benefit the diagnosis and prevention of birth defects.
The cellular composition of the lung lining fluid gradually changes from bronchus to alveolus
Authors: Pouwels S. D. , Burgess Janette K. , Verschuuren Erik , Slebos Dirk-Jan
Published: November 2021

Although large advances have recently been made mapping out the cellular composition of lung tissue using single cell sequencing, the composition and distribution of the cellular elements within the lining fluid of the lung has not been extensively studied. Here, we assessed the cellular composition of the lung lining fluid by performing a differential cell analysis on bronchoalveolar lavage fluid (BALF) and epithelial lining fluid (ELF) at four different locations within the lung in post-lung transplantation patients. The percentage of neutrophils and lymphocytes is reduced in more distal regions of the lungs, while the percentage of macrophages increases in these more distal regions. These data provide valuable information to determine which lung lining fluid sampling technique and location is best to use for measuring specific factors and biomarkers, and to increase the understanding of different cell populations in specific lung regions.
Increased expression of TAZ and associated upregulation of PD-L1 in cervical cancer
Authors: Han Yanyan , Liu Dandan , Li Lianhong
Published: November 2021

Background

As an important component of the Hippo pathway, WW domain-containing transcription regulator 1 (TAZ), is a transcriptional coactivator that is responsible for the progression of various types of cancers. Programmed cell death protein 1 (PD-1) receptors in activated T cells and their ligand programming death force 1 (PD-L1) are the main checkpoint signals that control T cell activity. Studies have shown high levels of PD-L1 in various cancers and that PD-L1/PD-1 signals to evade T-cell immunity. Recent data have demonstrated that TAZ can regulate the characteristics of cancer cells via PD-L1. Cervical cancer is a common gynecological disease worldwide. In this study, we attempted to evaluate the effects of TAZ and PD-L1 on cervical cancer.

Methods

Hela cervical cancer cells were transfected with TAZ plasmid or TAZ siRNA or PD-L1 siRNA by using Lipofectamine 2000. The relationship between TAZ and PD-L1 in cervical cancer cells was determined by qRT-PCR and western blotting. The functional roles of TAZ were confirmed via CCK-8, Transwell and flow cytometry assays. Western blotting was utilized to observe the expression of BCL-2 and Caspase-3. The clinicopathological correlation of TAZ and PD-L1 was evaluated via relevant databases.

Result

TAZ is upregulated in cervical cancer and induces the growth and metastasis of cervical cancer cells by targeting PD-L1and inhibiting the ratio of apoptotic of cancer cells. High TAZ and PD-L1 expression was observed in different stage, grade, histological patterns, and ages of cervical cancer groups compared with normal cervix groups. Furthermore, high TAZ expression was positively correlated with the infiltration levels of immune cells and the expression of PD-L1.
One-photon red light-triggered disassembly of small-molecule nanoparticles for drug delivery
Authors: Long Kaiqi , Han Han , Kang Weirong , Lv Wen , Wang Lang , Wang Yufeng , Ge Liang , Wang Weiping
Published: November 2021

Background

Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet–triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states.

Results

Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo.

Conclusions

This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.

Graphical Abstract
Analysis of predictors of adherent perinephric fat and its impact on perioperative outcomes in laparoscopic partial nephrectomy: a retrospective case–control study
Authors: Fang Lu , Li Huan , Zhang Tao , Liu Rui , Zhang Taotao , Bi Liangkuan , Xie Dongdong , Wang Yi , Yu Dexin
Published: November 2021

Background

Adherent perinephric fat (APF), characterized by inflammatory fat surrounding the kidney, can limit the isolation of renal tumors and increase the operative difficulty in laparoscopic partial nephrectomy (LPN). The aim of this study was to investigate the predictors of APF and its impact on perioperative outcomes during LPN.

Methods

A total of 215 consecutive patients undergoing LPN for renal cell carcinoma (RCC) from January 2017 to June 2019 at our institute were included. We divided these patients into two groups according to the presence of APF. Radiographic data were retrospectively collected from preoperative cross-sectional imaging. The perioperative clinical parameters were compared between the two groups. Univariate and multivariate analyses were performed to evaluate the predictive factors of APF.

Results

APF was identified in 41 patients (19.1%) at the time of LPN. Univariate analysis demonstrated that APF was significantly correlated with the male gender (P = 0.001), higher body mass index (P = 0.002), lower preoperative estimated glomerular filtration rate (P = 0.004), greater posterior perinephric fat thickness (P< 0.001), greater perinephric stranding (P< 0.001), and higher Mayo Adhesive Probability (MAP) score (P< 0.001). The MAP score (P< 0.001) was the only variable that remained an independent predictor for APF in multivariate analysis. We found that patients with APF had longer operative times (P< 0.001), warm ischemia times (P = 0.001), and greater estimated blood loss (P = 0.003) than those without APF. However, there were no significant differences in surgical approach, transfusion rate, length of postoperative stay, complication rate, or surgical margin between the two groups.

Conclusions

Several specific clinical and radiographic factors including the MAP score can predict APF. The presence of APF is associated with an increased operative time, warm ischemia time, and greater estimated blood loss but has no impact on other perioperative outcomes in LPN.
Diet normalization or caloric restriction as a preconception care strategy to improve metabolic health and oocyte quality in obese outbred mice
Authors: Smits Anouk , Marei Waleed F. A. , De Neubourg Diane , Leroy Jo L. M. R.
Published: November 2021

Background

Maternal metabolic disorders are linked to reduced metabolic health and oocyte quality. Obese women are advised to lose weight before conception to increase pregnancy chances. However, as human studies show no univocal guidelines, more research is necessary to provide fundamental insights in the consequences of dietary weight loss on oocyte quality. Therefore, we investigated the impact of diet normalization or calorie restricted diet for two, four or six weeks, as preconception care intervention (PCCI), in obese mice on metabolic health and oocyte quality.

Methods

Outbred female mice were fed a control (CTRL) or high-fat (HF) diet for 7 weeks (7w). Afterwards, HF-mice were put on different PCCIs, resulting in four treatment groups: 1) control diet up to 13w, 2) HF diet up to 13w (HF_HF), switch from a HF (7w) to 3) an ad libitum control diet (HF_CTRL) or 4) 30% calorie restricted control diet (HF_CR) for two, four or six weeks. Body weight, metabolic health, oocyte quality and overall fertility results were assessed.

Results

Negative effects of HF diet on metabolic health, oocyte quality and pregnancy rates were confirmed. HF_CTRL mice progressively improved insulin sensitivity, glucose tolerance, serum insulin and cholesterol from PCCI w2 to w4. No further improvements in metabolic health were present at PCCI w6. However, PCCI w6 showed best oocyte quality improvements. Mature oocytes still showed elevated lipid droplet volume and mitochondrial activity but a significant reduction in ROS levels and ROS: active mitochondria ratio compared with HF_HF mice. HF_CR mice restored overall insulin sensitivity and glucose tolerance by PCCI w4. However, serum insulin, cholesterol and ALT remained abnormal. At PCCI w6, glucose tolerance was again reduced. However, only at PCCI w6, oocytes displayed reduced ROS levels and restored mitochondrial activity compared with HF_HF mice. In addition, at PCCI w6, both PCCI groups showed decreased mitochondrial ultrastructural abnormalities compared with the HF_HF group and restored pregnancy rates.

Conclusions

Diet normalization for 4 weeks showed to be the shortest, most promising intervention to improve metabolic health. Most promising improvements in oocyte quality were seen after 6 weeks of intervention in both PCCI groups. This research provides fundamental insights to be considered in developing substantiated preconception guidelines for obese women planning for pregnancy.
Anticoagulation may contribute to antimicrobial treatment of Lemierre syndrome: a case report
Authors: Ge Jie , Zhou Peipei , Yang Yifei , Xu Tianshu , Yang Xu
Published: November 2021

Background

Lemierre syndrome (LS) is characterized by multisystemic infection beginning in the oropharynx, local thrombophlebitis (typically, of the internal jugular vein) and peripheral embolism. No evidence-based guidelines exist for the management of this disease, and the use of anticoagulation therapy remains particularly controversial.

Case presentation

A 61-year-old man presenting with left neck swelling, odynophagia, and dyspnea underwent emergency surgery and received intravenous antibiotics. The primary infection was controlled on hospital day 5, but on day 6 sudden leukocytosis and hypoxemia were observed. CT angiography revealed an intraluminal filling defect in the pulmonary artery on day 8. LS was diagnosed and anticoagulation therapy was initiated. The WBC count, which had maintained its peak values in the previous 2 days, decreased instantly after initiation, and follow-up controls showed thrombus resolution.

Conclusions

Our case supports the notion that anticoagulation therapy may be a valid supplement to antimicrobial therapy in LS, especially in the presence of a possibly young thrombus as suggested by clinical worsening.
Monitoring coagulation-fibrinolysis activation prompted timely diagnosis of hemophagocytic lymphohistiocytosis-related disseminated intravascular coagulation
Authors: Ling Liqin , Huang Xunbei , Liu Chaonan , Liao Juan , Zhou Jing
Published: November 2021

Background

Timely diagnosis of disseminated intravascular coagulation (DIC) in hemophagocytic lymphohistiocytosis (HLH) patients is crucial but challenging, as HLH interferes with the results of the laboratory tests included in the DIC score system.

Case presentation

Here, we reported a case of lymphoma-associated HLH, in which coagulation-fibrinolysis activation /inhibition markers (TAT, tPAIC, and PIC), prompted timely diagnosis of early stage DIC (initial phase of microvascular thrombosis, yet non-overt), prior to the development of organ failures and/or bleedings.

Conclusions

This report highlights the importance of the implementation of new biomarkers (such as TAT, tPAIC, and PIC), into the diagnostic work-up for coagulation disorders. These biomarkers are directly suggestive of microthrombus formation, therefore they can be of paramount importance in diagnosing DIC with complicated etiologies, such as hematological diseases-related DIC.
Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial
Authors: Kim Julian O. , McDonald Megan O. , Ong Aldrich , Koul Rashmi , Dubey Arbind , Hunter William , Ahmed Shahida , Quon Harvey , Yee Don , Parliament Matthew , Sivananthan Gokulan , Danielson Brita , Rowe Lindsay , Ghosh Sunita , Usmani Nawaid
Published: November 2021

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.
Characteristics and outcomes analysis of ovarian Sertoli–Leydig cell tumors (SLCTs): analysis of 15 patients
Authors: Wang Guangning , Zhang Ran , Li Chuan , Chen Aiping
Published: November 2021

Introduction

Because of limited information of Sertoli–Leydig cell tumors (SLCTs), the objective aimed to describe clinical parameters, management and treatment results of SLCTs.

Material and methods

We retrospectively reviewed 15 cases with SLCTs, who were treated in the Affiliated Hospital of Qingdao University between 2009 and 2020. Data of clinical parameters and treatment was studied.

Results

The age ranged 25–69 years. Elevated testosterone was observed in 4 patients. FIGO-stage: 14 were at Ia(10 moderately differentiated, 3 poorly differentiated, 5 retiform pattern).1 was at Ic. Patients with retiform pattern were more likely to exhibit endocrine function (p = 0.019, w = 0.61) and tumor diameter was significantly bigger in no endocrine function (p = 0.012, d = 1.52). All patients received surgical treatment. 8 received postoperative chemotherapy. The median follow-up was 66 months (20–112 months). 1 patient relapsed within 36 months and received cytoreductive surgery. She survived without disease after recurrence treatment. Of 5 patients who performed fertility sparing surgeries with the desire of childbirth, 3 had full-term pregnancy and 1 experienced a miscarriage. Another one has not tried to conceive.

Conclusion

The prognosis of SLCTs is good. Our data showed patients with retiform pattern were more likely to exhibit endocrine function. The diameter of tumor was significantly bigger in no endocrine function. Conservative surgery is the preferred option for patients with the desire of fertility at stage Ia. Postoperative chemotherapy is advised to cases with high-risk factors, but the most effective chemotherapy regimen is still uncertain.
Secreted indicators of androgen receptor activity in breast cancer pre-clinical models
Authors: Hanamura Toru , Christenson Jessica L. , O’Neill Kathleen I. , Rosas Emmanuel , Spoelstra Nicole S. , Williams Michelle M. , Richer Jennifer K.
Published: November 2021

Purpose

Accumulating evidence has attracted attention to the androgen receptor (AR) as a biomarker and therapeutic target in breast cancer. We hypothesized that AR activity within the tumor has clinical implications and investigated whether androgen responsive serum factors might serve as a minimally invasive indicator of tumor AR activity.

Methods

Based on a comprehensive gene expression analysis of an AR-positive, triple negative breast cancer patient-derived xenograft (PDX) model, 163 dihydrotestosterone (DHT)-responsive genes were defined as an androgen responsive gene set. Among them, we focused on genes that were DHT-responsive that encode secreted proteins, namely KLK3, AZGP1 and PIP, that encode the secreted factors prostate specific antigen (PSA), zinc-alpha-2-glycoprotein (ZAG) and prolactin induced protein (PIP), respectively. Using AR-positive breast cancer cell lines representing all breast cancer subtypes, expression of candidate factors was assessed in response to agonist DHT and antagonist enzalutamide. Gene set enrichment analysis (GSEA) was performed on publically available gene expression datasets from breast cancer patients to analyze the relationship between genes encoding the secreted factors and other androgen responsive gene sets in each breast cancer subtype.

Results

Anti-androgen treatment decreased proliferation in all cell lines tested representing various tumor subtypes. Expression of the secreted factors was regulated by AR activation in the majority of breast cancer cell lines. In GSEA, the candidate genes were positively correlated with an androgen responsive gene set across breast cancer subtypes.

Conclusion

KLK3, AZGP1 and PIP are AR regulated and reflect tumor AR activity. Further investigations are needed to examine the potential efficacy of these factors as serum biomarkers.
The design of a Bayesian adaptive clinical trial of tranexamic acid in severely injured children
Authors: VanBuren John M. , Casper T. Charles , Nishijima Daniel K. , Kuppermann Nathan , Lewis Roger J. , Dean J. Michael , McGlothlin Anna ,   For the TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN)
Published: November 2021

Background

Trauma is the leading cause of death and disability in children in the USA. Tranexamic acid (TXA) reduces the blood transfusion requirements in adults and children during surgery. Several studies have evaluated TXA in adults with hemorrhagic trauma, but no randomized controlled trials have occurred in children with trauma. We propose a Bayesian adaptive clinical trial to investigate TXA in children with brain and/or torso hemorrhagic trauma.

Methods/design

We designed a double-blind, Bayesian adaptive clinical trial that will enroll up to 2000 patients. We extend the traditional Emax dose-response model to incorporate a hierarchical structure so multiple doses of TXA can be evaluated in different injury populations (isolated head injury, isolated torso injury, or both head and torso injury). Up to 3 doses of TXA (15 mg/kg, 30 mg/kg, and 45 mg/kg bolus doses) will be compared to placebo. Equal allocation between placebo, 15 mg/kg, and 30 mg/kg will be used for an initial period within each injury group. Depending on the dose-response curve, the 45 mg/kg arm may open in an injury group if there is a trend towards increasing efficacy based on the observed relationship using the data from the lower doses. Response-adaptive randomization allows each injury group to differ in allocation proportions of TXA so an optimal dose can be identified for each injury group. Frequent interim stopping periods are included to evaluate efficacy and futility. The statistical design is evaluated through extensive simulations to determine the operating characteristics in several plausible scenarios. This trial achieves adequate power in each injury group.

Discussion

This trial design evaluating TXA in pediatric hemorrhagic trauma allows for three separate injury populations to be analyzed and compared within a single study framework. Individual conclusions regarding optimal dosing of TXA can be made within each injury group. Identifying the optimal dose of TXA, if any, for various injury types in childhood may reduce death and disability.
The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
Authors: Mitra Anita , MacIntyre David A. , Paraskevaidi Maria , Moscicki Anna-Barbara , Mahajan Vishakha , Smith Ann , Lee Yun S. , Lyons Deirdre , Paraskevaidis Evangelos , Marchesi Julian R. , Bennett Phillip R. , Kyrgiou Maria
Published: November 2021

Background

Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines.

Methods

We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.

Results

Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment.

Conclusions

Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.
Acute psychosis and serotonin syndrome in the setting of “Triple-C” overdose: a case report
Authors: Bachar Roudi , Majewski John Robert , Shrack Christopher , El-Khoury Anthony
Published: November 2021

Background

Over-the-counter medication overdose is a difficult diagnostic challenge for many physicians as common drug screening assays cannot detect these substances. We present a case of acute psychosis, serotonin syndrome, and anticholinergic overdose-like properties in the setting of Coricidin HBP Cough & Cold tablets, known by their street name Triple-C. This is the first case report we are aware of involving a patient presenting with these symptoms and requiring critical-care-level support.

Case presentation

A 31-year-old African American female with a past medical history of anxiety, childhood asthma, previous methamphetamine abuse, and coronavirus disease 2019 infection in August 2020 was brought to the emergency department by the local police department with altered mental status. Initial blood work, including extended drug screens, were unremarkable for a definitive diagnosis. This patient required critical-care-level support and high sedation because of her symptoms. Collateral history revealed the patient regularly consumed Triple-C daily for the 6 weeks prior to admission. A trial off sedation was attempted after 24 hours with no complications. The patient admitted to regular Triple-C consumption and auditory hallucinations since adolescence. She was discharged safely after 48 hours back into the community. She was lost to follow-up with psychiatry and internal medicine; however, she was evaluated in the emergency room 1 month later with a similar psychiatric presentation.

Conclusion

Overdose of Triple-C should be kept in the differential diagnosis of patients presenting with a triad of psychosis, serotonin syndrome, and anticholinergic overdose, in the setting of unknown substance ingestion.
Single-cell RNA-seq of out-of-thaw mesenchymal stromal cells shows tissue-of-origin differences and inter-donor cell-cycle variations
Authors: Medrano-Trochez Camila , Chatterjee Paramita , Pradhan Pallab , Stevens Hazel Y. , Ogle Molly E. , Botchwey Edward A. , Kurtzberg Joanne , Yeago Carolyn , Gibson Greg , Roy Krishnendu
Published: November 2021

Background

Human Mesenchymal stromal cells (hMSCs) from various tissue sources are widely investigated in clinical trials. These MSCs are often administered to patients immediately after thawing the cryopreserved product (out-of-thaw), yet little is known about the single-cell transcriptomic landscape and tissue-specific differences of out-of-thaw human MSCs.

Methods

13 hMSC samples derived from 10 “healthy” donors were used to assess donor variability and tissue-of-origin differences in single-cell gene expression profiles. hMSCs derived and expanded from the bone marrow (BM) or cord tissue (CT) underwent controlled-rate freezing for 24 h. Cells were then transferred to the vapor phase of liquid nitrogen for cryopreservation. hMSCs cryopreserved for at least one week, were characterized immediately after thawing using a droplet-based single-cell RNA sequencing method. Data analysis was performed with SC3 and SEURAT pipelines followed by gene ontology analysis.

Results

scRNA-seq analysis of the hMSCs revealed two major clusters of donor profiles, which differ in immune-signaling, cell surface properties, abundance of cell-cycle related transcripts, and metabolic pathways of interest. Within-sample transcriptomic heterogeneity is low. We identified numerous differentially expressed genes (DEGs) that are associated with various cellular functions, such as cytokine signaling, cell proliferation, cell adhesion, cholesterol/steroid biosynthesis, and regulation of apoptosis. Gene-set enrichment analyses indicated different functional pathways in BM vs. CT hMSCs. In addition, MSC-batches showed significant variations in cell cycle status, suggesting different proliferative vs. immunomodulatory potential. Several potential transcript-markers for tissue source differences were identified for further investigation in future studies. In functional assays, both BM and CT MSCs suppressed macrophage TNFα secretion upon interferon stimulation. However, differences between donors, tissue-of-origin, and cell cycle are evident in both TNF suppression and cytokine secretion.

Conclusions

This study shows that donor differences in hMSC transcriptome are minor relative to the intrinsic differences in tissue-of-origin. hMSCs with different transcriptomic profiles showed potential differences in functional characteristics. These findings contribute to our understanding of tissue origin-based differences in out-of-thaw therapeutic hMSC products and assist in the identification of cells with immune-regulatory or survival potential from a heterogeneous MSC population. Our results form the basis of future studies in correlating single-cell transcriptomic markers with immunomodulatory functions.
PPARβ/δ accelerates bone regeneration in diabetic mellitus by enhancing AMPK/mTOR pathway-mediated autophagy
Authors: Chen Miao , Jing Dian , Ye Rui , Yi Jianru , Zhao Zhihe
Published: November 2021

Background

Diabetic patients are more vulnerable to skeletal complications. Peroxisome proliferators-activated receptor (PPAR) β/δ has a positive regulatory effect on bone turnover under physiologic glucose concentration; however, the regulatory effect in diabetes mellitus has not been investigated yet. Herein, we explored the effects of PPARβ/δ agonist on the regeneration of diabetic bone defects and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) under a pathological high-glucose condition.

Methods

We detected the effect of PPARβ/δ agonist on osteogenic differentiation of rBMSCs in vitro and investigated the bone healing process in diabetic rats after PPARβ/δ agonist treatment in vivo. RNA sequencing was performed to detect the differentially expressed genes and enriched pathways. Western blot was performed to detect the autophagy-related protein level. Laser confocal microscope (LSCM) and transmission electron microscope (TEM) were used to observe the formation of autophagosomes.

Results

Our results demonstrated that the activation of PPARβ/δ can improve the osteogenic differentiation of rBMSCs in high-glucose condition and promote the bone regeneration of calvarial defects in diabetic rats, while the inhibition of PPARβ/δ alleviated the osteogenic differentiation of rBMSCs. Mechanistically, the activation of PPARβ/δ up-regulates AMPK phosphorylation, yielding mTOR suppression and resulting in enhanced autophagy activity, which further promotes the osteogenic differentiation of rBMSCs in high-glucose condition. The addition of AMPK inhibitor Compound C or autophagy inhibitor 3-MA inhibited the osteogenesis of rBMSCs in high-glucose condition, suggesting that PPARβ/δ agonist promotes osteogenic differentiation of rBMSCs through AMPK/mTOR-regulated autophagy.

Conclusion

In conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time.
Efficacy of posterior capsular release for flexion contracture in posterior-stabilized total knee arthroplasty
Authors: Kinoshita Tomofumi , Hino Kazunori , Kutsuna Tatsuhiko , Watamori Kunihiko , Tsuda Takashi , Miura Hiromasa
Published: November 2021

Purpose

Posterior capsular contracture causes stiffness during knee extension in knee osteoarthritis. Furthermore, in posterior-stabilized total knee arthroplasty (PS-TKA), a unique design such as the cam mechanism could conflict with the posterior capsule (PC) causing flexion contracture (FC). However, few studies have focused on the anatomical aspects of the PC. This study aimed to investigate the anatomical site and forms of posterior capsular attachment to the femoral cortex, and to evaluate the efficacy of posterior capsular release for FC by assessing changes in knee extension angles using a navigation system.

Methods

Attachment sites of the PC were investigated in 10 cadaveric knees using computed tomography. PS-TKA was performed in six cadaveric knees using a navigation system to evaluate the efficacy of posterior capsular release for FC. Posterior capsular release was performed stepwise at each part of the femoral condyle.

Results

The gastrocnemius tendon and PC were integrally attached to the femoral cortex at the medial and lateral condyles, whereas the PC at the intercondylar fossa was independently attached directly to the femoral cortex. Moreover, the PC at the intercondylar fossa was attached most distally among each femoral condyle. Posterior capsular release at the intercondylar fossa allowed 11.4° ± 2.8° improvement in knee extension. This angle was further improved by 5.5° ± 1.3°, after subsequent capsular release at the medial and lateral condyles.

Conclusion

The forms and sites of posterior capsular attachment differed based on the part of the femoral condyle. Stepwise posterior capsular release was effective for FC in PS-TKA.

Level of evidence

III.
Genome-wide identification and characteristic analysis of the downstream melatonin metabolism gene GhM2H in Gossypium hirsutum L.
Authors: Zhang Yuexin , Wang Jing , Chen Xiugui , Lu Xuke , Wang Delong , Wang Junjuan , Wang Shuai , Chen Chao , Guo Lixue , Malik Waqar Afzal , Fan Yapeng , Rui Cun , Cui Ruifeng , Wang Qinqin , Lei Yuqian , Ye Wuwei
Published: November 2021

Background

Melatonin 2-hydroxylase (M2H) is the first enzyme in the catabolism pathway of melatonin, which catalyzes the production of 2-hydroxymelatonin (2-OHM) from melatonin. The content of 2-hydroxymelatonin in plants is much higher than that of melatonin. So M2H may be a key enzyme in the metabolic pathway of melatonin.

Method

We conducted a systematic analysis of the M2H gene family in Gossypium hirsutum based on the whole genome sequence by integrating the structural characteristics, phylogenetic relationships, expression profile, and biological stress of the members of the Gossypium hirsutum M2H gene family.

Result

We identified 265 M2H genes in the whole genome of Gossypium hirsutum, which were divided into 7 clades (clades I-VII) according to phylogenetic analysis. Most M2H members in each group had similar motif composition and gene structure characteristics. More than half of GhM2H members contain ABA-responsive elements and MeJA-responsive elements. Under different stress conditions, the expression levels of the gene changed, indicating that GhM2H members were involved in the regulation of abiotic stress. Some genes in the GhM2H family were involved in regulating melatonin levels in cotton under salt stress, and some genes were regulated by exogenous melatonin.

Conclusion

This study is helpful to explore the function of GhM2H, the downstream metabolism gene of melatonin in cotton, and lay the foundation for better exploring the molecular mechanism of melatonin improving cotton's response to abiotic stress.
Shoulder pain prevalence by age and within occupational groups: a systematic review
Authors: Hodgetts Christopher J. , Leboeuf-Yde Charlotte , Beynon Amber , Walker Bruce F.
Published: November 2021

Background

Shoulder pain was previously shown to diminish in older populations and it was suggested that this could be explained by reduced usage with age. Our objectives were to investigate if estimates of shoulder pain continue to increase after the age of 50 in working populations and to compare these estimates in physically demanding occupations with sedentary occupations.

Methods

A systematic review of retrospective, cross-sectional, prospective, or longitudinal.

studies reporting prevalence or incidence of non-specific shoulder pain in occupational groups stratified by age. Searches were conducted in PubMed, Scopus, and CINAHL from inception until January 2020. Study characteristics and prevalence estimates stratified by age were extracted. Two reviewers independently performed a critical analysis of the included studies to determine their validity and risk of bias.

Results

Twenty studies with a total of 40,487 participants and one study of a clinical data base were included and assigned a direction of the estimates for shoulder pain as either ‘increasing’, ‘remaining stable’ or ‘decreasing’ past the age of 50. Shoulder pain generally increased past 50, with 16 of the 21 included studies reporting higher estimates/odds ratios in older participants. In the more physically active occupations over 50, the estimates increased in 14 of the 18 samples compared to only two of the four involving sedentary occupations.

Conclusions

Shoulder pain prevalence remains common in workers beyond the age of 50. Prevalence continues to increase in physically demanding occupations. Clinicians should consider factors of occupation when managing shoulder pain.

Trial registration

PROSPERO (CRD42019137831).
Enhancer analysis of the Drosophila zinc finger transcription factor Earmuff by gene targeting
Authors: Hildebrandt Kirsten , Kübel Sabrina , Minet Marie , Fürst Nora , Klöppel Christine , Steinmetz Eva , Walldorf Uwe
Published: November 2021

Background

Many transcription factors are involved in the formation of the brain during the development of Drosophila melanogaster. The transcription factor Earmuff (Erm), a member of the forebrain embryonic zinc finger family (Fezf), is one of these important factors for brain development. One major function of Earmuff is the regulation of proliferation within type II neuroblast lineages in the brain; here, Earmuff is expressed in intermediate neural progenitor cells (INPs) and balances neuronal differentiation versus stem cell maintenance. Erm expression during development is regulated by several enhancers.

Results

In this work we show a functional analysis of erm and some of its enhancers. We generated a new erm mutant allele by gene targeting and reintegrated Gal4 to make an erm enhancer trap strain that could also be used on an erm mutant background. The deletion of three of the previously analysed enhancers showing the most prominent expression patterns of erm by gene targeting resulted in specific temporal and spatial defects in defined brain structures. These defects were already known but here could be assigned to specific enhancer regions.

Conclusion

This analysis is to our knowledge the first systematic analysis of several large enhancer deletions of a Drosophila gene by gene targeting and will enable deeper analysis of erm enhancer functions in the future.
Clinical evaluation of pregnant women with SARS-COV2 pneumonia: a real-life study from Egypt
Authors: Zaky Samy , Hosny Hossam , Elassal Gehan , Asem Noha , Baki Amin Abdel , Kamal Ehab , Abdelbary Akram , Said Ahmad , Ibrahim Hamdy , Taema Khaled , Amin Wagdy , Abd-Elsalam Sherief , Soliman Shaimaa , Abdelmenam Hend Salah , Mohamed Ahmed S. , Elnady Mohamed , Hassany Mohamed , Zaid Hala
Published: November 2021

Background

Knowledge about the outcome of COVID-19 on pregnant women is so important. The published literature on the outcomes of pregnant women with COVID-19 is confusing. The aim of this study was to report our clinical experience about the effect of COVID-19 on pregnant women and to determine whether it was associated with increased mortality or an increase in the need for mechanical ventilation in this special category of patients.

Methods

This was a cohort study from some isolation hospitals of the Ministry of Health and Population, in eleven governorates, Egypt. The clinical data from the first 64 pregnant women with COVID-19 whose care was managed at some of the Egyptian hospitals from 14 March to 14 June 2020 as well as 114 non-pregnant women with COVID-19 was reviewed.

Results

The two groups did not show any significant difference regarding the main outcomes of the disease. Two cases in each group needed mechanical ventilation (p 0.617). Three cases (4.7%) died among the pregnant women and two (1.8%) died among the non-pregnant women (p 0.352).

Conclusions

The main clinical outcomes of COVID-19 were not different between pregnant and non-pregnant women with COVID-19. Based on our findings, pregnancy did not exacerbate the course or mortality of COVID-19 pneumonia.
Unraveling differences in fecal microbiota stability in mammals: from high variable carnivores and consistently stable herbivores
Authors: Zoelzer Franziska , Burger Anna Lena , Dierkes Paul Wilhelm
Published: November 2021

Background

Through the rapid development in DNA sequencing methods and tools, microbiome studies on a various number of species were performed during the last decade. This advance makes it possible to analyze hundreds of samples from different species at the same time in order to obtain a general overview of the microbiota. However, there is still uncertainty on the variability of the microbiota of different animal orders and on whether certain bacteria within a species are subject to greater fluctuations than others. This is largely due to the fact that the analysis in most extensive comparative studies is based on only a few samples per species or per study site. In our study, we aim to close this knowledge gap by analyzing multiple individual samples per species including two carnivore suborders Canoidea and Feloidea as well as the orders of herbivore Perissodactyla and Artiodactyla held in different zoos. To assess microbial diversity, 621 fecal samples from 31 species were characterized by sequencing the V3–V4 region of the 16S rRNA gene using Illumina MiSeq.

Results

We found significant differences in the consistency of microbiota composition and in fecal microbial diversity between carnivore and herbivore species. Whereas the microbiota of Carnivora is highly variable and inconsistent within and between species, Perissodactyla and Ruminantia show fewer differences across species boundaries. Furthermore, low-abundance bacterial families show higher fluctuations in the fecal microbiota than high-abundance ones.

Conclusions

Our data suggest that microbial diversity is significantly higher in herbivores than in carnivores, whereas the microbiota in carnivores, unlike in herbivores, varies widely even within species. This high variability has methodological implications and underlines the need to analyze a minimum amount of about 10 samples per species. In our study, we found considerable differences in the occurrence of different bacterial families when looking at just three and six samples. However, from a sample number of 10 onwards, these within-species fluctuations balanced out in most cases and led to constant and more reliable results.
After 25 years of computer-navigated total knee arthroplasty, where do we stand today?
Authors: Shah Siddharth M.
Published: November 2021

Background

Limb and implant alignment along with soft tissue balance plays a vital role in the outcomes after total knee arthroplasty (TKA). Computer navigation for TKA was first introduced in 1997 with the aim of implanting the prosthetic components with accuracy and precision. This review discusses the technique, current status, and scientific evidence pertaining to computer-navigated TKA.

Body

The adoption of navigated TKA has slowly but steadily increased across the globe since its inception 25 years ago. It has been more rapid in some countries like Australia than others, like the UK. Contemporary, large console-based navigation systems help control almost every aspect of TKA, including the depth and orientation of femoral and tibial resections, soft-tissue release, and customization of femoral and tibial implant positions in order to obtain desired alignment and balance. Navigated TKA results in better limb and implant alignment and reduces outliers as compared to conventional TKA. However, controversy still exists over whether improved alignment provides superior function and longevity. Surgeons may also be hesitant to adopt this technology due to the associated learning curve, slightly increased surgical time, fear of pin site complications, and the initial set-up cost. Furthermore, the recent advent of robotic-assisted TKA which provides benefits like precision in bone resections and avoiding soft-tissue damage due to uncontrolled sawing, in addition to those of computer navigation, might be responsible for the latter technology taking a backseat.

Conclusion

This review summarizes the current state of computer-navigated TKA. The superiority of computer navigation to conventional TKA in improving accuracy is well established. Robotic-assisted TKA provides enhanced functionality as compared to computer navigation but is significantly more expensive. Whether robotic-assisted TKA offers any substantive advantages over navigation is yet to be conclusively proven. Irrespective of the form, the use of computer-assisted TKA is on the rise worldwide and is here to stay.