bluuebunny/crossref_metadata_2025 huggingface dataset:
Gorham-Stout case report: a multi-omic analysis reveals recurrent fusions as new potential drivers of the disease
Authors: Yébenes Mayordomo Marcos , Al Shboul Sofian , Gómez-Herranz Maria , Azfer Asim , Meynert Alison , Salter Donald , Hayward Larry , Oniscu Anca , Patton James T. , Hupp Ted , Arends Mark J. , Alfaro Javier Antonio
Published: June 2022

Background

Gorham-Stout disease is a rare condition characterized by vascular proliferation and the massive destruction of bone tissue. With less than 400 cases in the literature of Gorham-Stout syndrome, we performed a unique study combining whole-genome sequencing and RNA-Seq to probe the genomic features and differentially expressed pathways of a presented case, revealing new possible drivers and biomarkers of the disease.

Case presentation

We present a case report of a white 45-year-old female patient with marked bone loss of the left humerus associated with vascular proliferation, diagnosed with Gorham-Stout disease. The analysis of whole-genome sequencing showed a dominance of large structural DNA rearrangements. Particularly, rearrangements in chromosomes seven, twelve, and twenty could contribute to the development of the disease, especially a gene fusion involvingATG101that could affect macroautophagy. The study of RNA-sequencing data from the patient uncovered thePI3K/AKT/mTORpathway as the most affected signaling cascade in the Gorham-Stout lesional tissue. Furthermore, M2 macrophage infiltration was detected using immunohistochemical staining and confirmed by deconvolution of the RNA-seq expression data.

Conclusions

The way that DNA and RNA aberrations lead to Gorham-Stout disease is poorly understood due to the limited number of studies focusing on this rare disease. Our study provides the first glimpse into this facet of the disease, exposing new possible therapeutic targets and facilitating the clinicopathological diagnosis of Gorham-Stout disease.
BidSi6 and BidEL isoforms as a potential marker for predicting colorectal adenomatous polyps
Authors: Forouzesh Flora , Kia Fatemeh Sadat , Nazemalhosseini-Mojarad Ehsan
Published: June 2022

Background

As a well-known protein, Bid links the extrinsic and intrinsic apoptotic pathways and plays important roles in cell proliferation. In this study, we evaluated the expression of two isoforms of the Bid gene (BidSi6 and BidEL) in colorectal adenomatous polyps as a biomarker and investigated the relationship between their expression levels with clinicopathological factors.

Methods

The expression of BidSi6 and BidEL isoforms in 22 pairs of Adenomatous polyps and adjust non-polyp tissues was measured by qReal-Time PCR and compared with 10 normal colon tissues. ROC curve was performed to examine the diagnostic capacity. Also, sequencing was performed for molecular identification of BidSi6 isoform in adenomatous polyp.

Results

Our results showed that BidSi6 and BidEL isoforms were significantly overexpressed in Adenomatous polyps and non-polyp adjacent tissues from the same patients compared to that in normal colon tissues, but there was no significant expression between polyps and adjust non-polyp tissues. There were no significant correlations between the expression of two isoforms and other features of clinicopathology. The area under the curve of BidSi6 and BidEL isoforms indicated powerful diagnostic capability. The phylogenetic tree was constructed based on the sequence of idSi6 isoform, and the results showed that adenomatous polyp tissue and adjust non-polyp tissue were separated from healthy colorectal tissue and reference sequence (EU678292).

Conclusions

These findings suggest that BidSi6 and BidEL isoforms can be used as new potential biomarkers in adenomatous polyps.
Association between the severity of metabolic dysfunction-associated fatty liver disease and the risk of colorectal neoplasm: a systematic review and meta-analysis
Authors: Zeng Yunqing , Cao Ruyue , Tao Ziwen , Gao Yanjing
Published: June 2022

Background

The severity of metabolic dysfunction-associated fatty liver disease (MAFLD) reportedly plays a part in the etiology of colorectal tumors. However, there is no consensus.

Methods

Studies relevant with the impact of MAFLD severity on the risk of colorectal neoplasms published before 24th April 2022 were screened. The pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was obtained using standard and cumulative meta-analyses. Subgroup, meta-regression, and sensitivity analyses were carried out to identify heterogeneity.

Results

Fourteen studies with data from 37,824 MAFLD patients were included. The prevalence of colorectal neoplasms escalated with the progression of MAFLD compared to simple steatosis (OR = 1.93; 95% CI = 1.42–2.62). The magnitude and direction of the effect on these outcomes remained largely constant over time. Even after limiting the meta-analysis to 8 studies with available adjusted OR (aOR), the findings still suggested that MAFLD severity was positively related to colorectal neoplasms (aOR = 3.03; 95% CI = 2.02–4.53). Severe MAFLD was more likely to cause left colon tumors (OR = 3.86, 95% CI = 2.16–6.91) than right colon neoplasms (OR = 1.94, 95% CI = 1.15–3.28).

Conclusion

The severity of MAFLD was independently related to colorectal neoplasms and severe MAFLD was more likely to cause left colon tumors.
Three-port single-intercostal versus uniportal thoracoscopic segmentectomy for the treatment of lung cancer: a propensity score matching analysis
Authors: Sun Keyi , Wu Zixiang , Wang Qi , Wu Ming
Published: June 2022

Background

The purpose of this retrospective study was to demonstrate the safety and feasibility of three-port single-intercostal video-assisted thoracoscopic surgery (SIC-VATS) segmentectomy compared to uniportal video-assisted thoracoscopic surgery (UVATS) segmentectomy.

Methods

We included 544 patients diagnosed with cT1N0M0 non-small-cell lung cancer (NSCLC) who underwent thoracoscopic segmentectomy between January 2020 and August 2021, including 147 and 397 patients who underwent three-port SIC-VATS and UVATS, respectively. After incorporating preoperative clinical variables, we compared surgical outcomes and perioperative indicators between the two groups by propensity score matching analysis.

Results

After 1:1 propensity score matching, each group comprised 143 patients with no significant differences in baseline demographics and characteristics. There was no significant difference in operative time (p = 0.469), blood loss (p = 0.501), number of dissected lymph nodes (p = 0.228), dwell time of the main chest drain (p = 0.065), hospital stay (p = 0.243), or major complication rate (p = 0.295) between the three-port SIC-VATS and UVATS groups.

Conclusions

The three-port SIC-VATS was as safe and feasible as UVATS for patients who are diagnosed with early-stage NSCLC.
Comparison of the efficacy and safety of repeated hepatectomy and radiofrequency ablation in the treatment of primary recurrent liver cancer: a meta-analysis
Authors: Chen Zhichao , Wang Jiefang , Lin Yonghua
Published: June 2022

Background

Since there is still controversy about the comparison of the efficacy and safety of RH and RFA in the treatment of recurrent liver cancer, we conducted a meta-analysis to compare the efficacy and safety, in order to provide evidence-based evidence for future research and clinical treatment.

Methods

We searched PubMed, Embase, and Cochrane Library from the establishment of the database to Feb 2021. We included studies that reported liver cancer patients underwent repeated hepatectomy (RH) or radiofrequency ablation (RFA), and we excluded duplicate publications, research without full text, incomplete information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. The STATA 15.1 was used to analyze the data.

Results

The pooled results show that the 3-year and 5-year overall survival (OS) rate of the repeated hepatectomy group was significantly higher than the radiofrequency ablation group (odds ratio (OR) = 1.95, 95% confidence interval (CI):1.47–2.60, P ≤ 0.001; OR = 1.65, 95% CI: 1.12–2.43, P = 0.012). Similarly, the pooled results show that the 3-year and 5-year disease-free survival (DFS) rate of the repeated hepatectomy group was significantly higher than the radiofrequency ablation group (OR = 1.73, 95% CI: 1.30–2.31, P ≤ 0.001; OR = 1.84, 95% CI: 1.38–2.49, P ≤ 0.001). However, there is no significant difference in the 1-year OS and DFS rate of repeated hepatectomy group and radiofrequency ablation group. Additionally, the pooled results show that the postoperative Clavien-Dindo (CD) grade II or higher complication rate of the repeated hepatectomy group was significantly higher than the radiofrequency ablation group (OR = 2.80, 95% CI: 1.37–5.75, P = 0.005).

Conclusion

Based on the pooled results of 8 existing retrospective studies, RH has a higher OS rate and DFS rate in the treatment of recurrent liver cancer, while the postoperative complication rate of RFA is lower. When survival is the primary goal, RH should be the first choice for recurrent liver cancer.
The circadian clock protein Rev-erbα provides neuroprotection and attenuates neuroinflammation against Parkinson’s disease via the microglial NLRP3 inflammasome
Authors: Kou Liang , Chi Xiaosa , Sun Yadi , Han Chao , Wan Fang , Hu Junjie , Yin Sijia , Wu Jiawei , Li Yunna , Zhou Qiulu , Zou Wenkai , Xiong Nian , Huang Jinsha , Xia Yun , Wang Tao
Published: June 2022

Background

Circadian disturbance is a common nonmotor complaint in Parkinson’s disease (PD). The molecular basis underlying circadian rhythm in PD is poorly understood. Neuroinflammation has been identified as a key contributor to PD pathology. In this study, we explored the potential link between the core clock molecule Rev-erbα and the microglia-mediated NLR family pyrin domain-containing 3 (NLRP3) inflammasome in PD pathogenesis.

Methods

We first examined the diurnal Rev-erbα rhythms and diurnal changes in microglia-mediated inflammatory cytokines expression in the SN of MPTP-induced PD mice. Further, we used BV2 cell to investigate the impacts of Rev-erbα on NLRP3 inflammasome and microglial polarization induced by 1-methyl-4-phenylpyridinium (MPP+) and αsyn pre-formed fibril. The role of Rev-erbα in regulating microglial activation via NF-κB and NLRP3 inflammasome pathway was then explored. Effects of SR9009 against NLRP3 inflammasome activation, microgliosis and nigrostriatal dopaminergic degeneration in the SN and striatum of MPTP-induced PD mice were studied in detail.

Results

BV2 cell-based experiments revealed the role of Rev-erbα in regulating microglial activation and polarization through the NF-κB and NLRP3 inflammasome pathways. Circadian oscillation of the core clock gene Rev-erbα in the substantia nigra (SN) disappeared in MPTP-induced PD mice, as well as diurnal changes in microglial morphology. The expression of inflammatory cytokines in SN of the MPTP-induced mice were significantly elevated. Furthermore, dopaminergic neurons loss in the nigrostriatal system were partially reversed by SR9009, a selective Rev-erbα agonist. In addition, SR9009 effectively reduced the MPTP-induced glial activation, microglial polarization and NLRP3 inflammasome activation in the nigrostriatal system.

Conclusions

These observations suggest that the circadian clock protein Rev-erbα plays an essential role in attenuating neuroinflammation in PD pathology, and provides a potential therapeutic target for PD treatment.
Latinx individuals’ knowledge of, preferences for, and experiences with prenatal genetic testing: a scoping review
Authors: Grafft Natalie , Dwyer Andrew A. , Pineros-Leano María
Published: June 2022

Background

The American College of Obstetricians and Gynecologists recommends prenatal genetic testing (PGT) be offered to all pregnant persons regardless of known risk factors. However, significant racial/ethnic differences exist regarding acceptance of PGT contributing to disparities. Latinas (Latinx), one of the fastest growing ethnic groups in the United States, have low PGT acceptance rates. This systematic scoping review aimed to provide a landscape of existing literature on Latinx individuals’ knowledge of, preferences for, and experiences with prenatal and preconception genetic testing. Synthesizing the current state of the science may inform development of culturally tailored interventions to support high-quality PGT decisions (e.g., informed, aligned with a pregnant persons’ values).

Methods

We conducted a structured, systematic literature search of published articles and gray literature in electronic databases (PubMed, PsycINFO, CINAHL, Medline, Embase, Eric, Social Services Abstracts, and PsycArticles). Articles in English published prior to March 2021 were retrieved relating to genetics, pregnancy, and Latina women. Articles underwent title, abstract and full-text review by independent investigators to assess inclusion and exclusion criteria. Risk of bias was evaluated by two investigators. Iterative thematic analysis was employed to group study findings into themes to identify possible targets for interventions.

Results

The search generated 5511 unique articles. After title screening, 335 underwent abstract review and subsequently 61 full-text review. Twenty-eight studies met inclusion criteria and 7 additional studies were included after reviewing reference lists. Three overarching themes emerged: genetic knowledge/literacy (26/35, 74%), provider (mis)communication/patient satisfaction (21/35, 60%), and cross-cultural beliefs (12/35, 34%). Studies indicate discordant patient-provider language (n = 5), miscommunication (n = 4), and lack of concordant decision-making (n = 4) pose barriers to high-quality PGT decisions. Immigration status (n = 1) and religious beliefs (n = 5) are additional factors influencing PGT decisions.

Conclusions

Identified studies suggest that cultural and linguistic factors affect Latinx PGT decision-making. Latinx individual’s comprehension and recall of PGT information is enhanced by culturally and linguistically concordant providers—suggesting that culturally-informed interventions may enhance PGT acceptability and support high-quality decisions. Future directions to surmount PGT disparities may include community health workers and cultural brokers to empower Latinx people to make informed decisions aligned with their values and preferences.
The effect of national antenatal care guidelines and provider training on obstetric danger sign counselling: a propensity score matching analysis of the 2014 Ethiopia service provision assessment plus survey
Authors: Yeneabat Tebikew , Hayen Andrew , Getachew Theodros , Dawson Angela
Published: June 2022

Background

Most pregnant women in low and lower-middle-income countries do not receive all components of antenatal care (ANC), including counselling on obstetric danger signs. Facility-level ANC guidelines and provider in-service training are major factors influencing ANC counselling. In Ethiopia, little is known about the extent to which guidelines and provider in-service training can increase the quality of ANC counselling.

Methods

We examined the effect of national ANC guidelines and ANC provider in-service training on obstetric danger sign counselling for pregnant women receiving ANC using the 2014 Ethiopian service provision assessment plus (ESPA +) survey data. We created two analysis samples by applying a propensity score matching method. The first sample consisted of women who received ANC at health facilities with guidelines matched with those who received ANC at health facilities without guidelines. The second sample consisted of women who received ANC from the providers who had undertaken in-service training in the last 24 months matched with women who received ANC from untrained providers. The outcome variable was the number of obstetric danger signs described during ANC counselling, ranging from zero to eight. The covariates included women’s socio-demographic characteristics, obstetric history, health facility characteristics, and ANC provider characteristics.

Results

We found that counselling women about obstetric danger signs during their ANC session varied according to the availability of ANC guidelines (61% to 70%) and provider training (62% to 68%). After matching the study participants by the measured covariates, the availability of ANC guidelines at the facility level significantly increased the average number of obstetric danger signs women received during counselling by 24% (95% CI: 12–35%). Similarly, providing refresher training for ANC providers increased the average number of obstetric danger signs described during counselling by 37% (95% CI: 26–48%).

Conclusion

The findings suggest that the quality of ANC counselling in Ethiopia needs strengthening by ensuring that ANC guidelines are available at every health facility and that the providers receive regular ANC related in-service training.
Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus
Authors: Andreassen Søren N. , Toft-Bertelsen Trine L. , Wardman Jonathan H. , Villadsen René , MacAulay Nanna
Published: June 2022

Background

Dysregulation of brain fluid homeostasis associates with brain pathologies in which fluid accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for pathologies with disturbed brain fluid homeostasis. Such lack of therapeutic targets originates, in part, from the incomplete map of the molecular mechanisms underlying cerebrospinal fluid (CSF) secretion by the choroid plexus.

Methods

The transcriptomic profile of rat choroid plexus was generated by RNA Sequencing (RNAseq) of whole tissue and epithelial cells captured by fluorescence-activated cell sorting (FACS), and compared to proximal tubules. The bioinformatic analysis comprised mapping to reference genome followed by filtering for type, location, and association with alias and protein function. The transporters and associated regulatory modules were arranged in discovery tables according to their transcriptional abundance and tied together in association network analysis.

Results

The transcriptomic profile of choroid plexus displays high similarity between sex and species (human, rat, and mouse) and lesser similarity to another high-capacity fluid-transporting epithelium, the proximal tubules. The discovery tables provide lists of transport mechanisms that could participate in CSF secretion and suggest regulatory candidates.

Conclusions

With quantification of the transport protein transcript abundance in choroid plexus and their potentially linked regulatory modules, we envision a molecular tool to devise rational hypotheses regarding future delineation of choroidal transport proteins involved in CSF secretion and their regulation. Our vision is to obtain future pharmaceutical targets towards modulation of CSF production in pathologies involving disturbed brain water dynamics.
Knowledge, perceptions, and attitudes by residents in Punjab and Khyber Pakhtunkhwa, Pakistan in connection with bats
Authors: Attaullah  , Ali Shahzad , Javid Arshad , Imran Muhammad , Khan Tahir Mehmood , Phelps Kendra , Olival Kevin J.
Published: June 2022

Background

Fruit bats play an important role in pollination and seed dispersal, and their conservation is important to maintain the productivity of some crops and natural ecosystems. The objective of this study was to investigate the knowledge, attitudes, and perception of fruit bats by orchard farmers and agricultural communities in Pakistan.

Methods

The present survey was conducted in two districts (i.e. Sheikhupura and Malakand districts) within Punjab and Khyber Pakhtunkhwa provinces based on the higher number of fruit growing areas and bat roosting sites. A total of 200 (100 per district) close-ended questionnaires with 53 questions were administered to randomly selected respondents within the selected communities associated with fruit orchards, including orchard owners, laborers, and members of the surrounding community. Each questionnaire was divided into seven sections (i.e., demographic information, environmental and public health effects of bats, knowledge about bats, perception and control of bats, non-lethal methods adopted to control bats, and different myths about bats).

Results

A majority of respondents (59%, n = 118) mis-classified bats as birds instead of mammals despite more than 84% reporting that they have observed bats. Nearly 71.5% of orchard farmers perceived that their fruits are contaminated by bats during consumption, and a majority believe that bats destroy orchards (62.5%) and are responsible for spreading disease. Mythology about bats was ambiguous, as 49% of those surveyed did not perceived bats to bring good luck (49%), and 50% did not perceived them to be bad omens either. Most respondents have never killed a bat (68%) nor would they kill a bat if given the opportunity (95%). Regarding the control of bats, the greatest percentage of respondents strongly disagree with shooting bats (36%) and strongly agree with leaving bats alone (42.5%).

Conclusions

This study provides a better understanding of the sociodemographic factors associated with knowledge, attitude and perception of bats from fruit orchard owners, labourers and local people. We recommend educational interventions for targeted groups in the community, highlighting the ecosystem services and importance of bat conservation to improve people’s current knowledge regarding the role of bats and reduce direct persecution against bats.
Initial clinical experience of surface guided stereotactic radiation therapy with open-face mask immobilization for improving setup accuracy: a retrospective study
Authors: Zhou Shun , Li Junyu , Zhu Xianggao , Du Yi , Yu Songmao , Wang Meijiao , Yao Kaining , Wu Hao , Yue Haizhen
Published: June 2022

Purpose

To propose a specific surface guided stereotactic radiotherapy (SRT) treatment procedure with open-face mask immobilization and evaluate the initial clinical experience in improving setup accuracy.

Methods and materials

The treatment records of 48 SRT patients with head lesions were retrospectively analyzed. For each patient, head immobilization was achieved with a double-shell open-face mask. The anterior shell was left open to expose the forehead, nose, eyes and cheekbones. The exposed facial area was used as region-of-interest for surface tracking by AlignRT (VisionRT Inc, UK). The posterior shell provided a sturdy and personalized headrest. Patient initial setup was guided by 6DoF real-time deltas (RTD) using the reference surface obtained from the skin contour delineated on the planning CT images. The endpoint of initial setup was 1 mm in translational RTD and 1 degree in rotational RTD. CBCT guidance was performed to derive the initial setup errors, and couch shifts for setup correction were applied prior to treatment delivery. CBCT couch shifts, AlignRT RTD values, repositioning rate and setup time were analyzed.

Results

The absolute values of median (maximal) CBCT couch shifts were 0.4 (1.3) mm in VRT, 0.1 (2.5) mm in LNG, 0.2 (1.6) mm in LAT, 0.1(1.2) degree in YAW, 0.2 (1.4) degree in PITCH and 0.1(1.3) degree in ROLL. The couch shifts and AlignRT RTD values exhibited highly agreement except in VRT and PITCH (p value < 0.01), of which the differences were as small as negligible. We did not find any case of patient repositioning that was due to out-of-tolerance setup errors, i.e., 3 mm and 2 degree. The surface guided setup time ranged from 52 to 174 s, and the mean and median time was 97.72 s and 94 s respectively.

Conclusions

The proposed surface guided SRT procedure with open-face mask immobilization is a step forward in improving patient comfort and positioning accuracy in the same process. Minimized initial setup errors and repositioning rate had been achieved with reasonably efficiency for routine clinical practice.
ECMO for paediatric cardiac arrest caused by bronchial rupture and severe lung injury: a case report about life-threatening rescue at an adult ECMO centre
Authors: Chu Xiaoqiong , Chen Weibiao , Wang Yafei , Zhu Luqi , Zhang Mengqin , Zhang Sheng
Published: June 2022

Background

Bronchial rupture in children is a rare but dangerous complication after chest trauma and is associated with increased mortality. Veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is reported as one of the treatments for this life-threatening complication.

Case presentation

A 4-year-old boy with bronchial rupture and traumatic wet lung complicated by cardiac arrest after chest trauma was admitted to an adult ECMO centre. He experienced two cardiac arrests, one before and one during the operation. The total duration of cardiac arrest was 30 min. V-V ECMO was initiated because of severe hypoxia and hypercapnia during the operation. ECMO was performed for 6 days, and mechanical ventilation lasted 11 days. On the 31st day after surgery, he had recovered completely and was discharged without neurological deficit.

Conclusion

V-V ECMO can be considered for supportive care in children with severe acute respiratory failure after bronchial rupture. In an emergency, V-V ECMO can be carried out effectively in a qualified and experienced adult ECMO centre. However, the application of ECMO in children is different from that in adults and requires more refined management.
Persimmon leaf extract alleviates chronic social defeat stress-induced depressive-like behaviors by preventing dendritic spine loss via inhibition of serotonin reuptake in mice
Authors: Yu Hui , Shao Shumin , Xu Junnan , Guo Haibiao , Zhong Zhangfeng , Xu Jiangping
Published: June 2022

Background

Fresh or dried Persimmon leaves (Diospyros kakiThunb.) exhibit preventive effects on cardiovascular and cerebrovascular diseases. However, their antidepressant effects and underlying mechanisms are unclear. Thus, we investigated mechanisms responsible for Persimmon leaf extract (PLE) activity on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice.

Methods

CSDS was used as a mouse model of depression. We performed the sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) to identify depressive-like behavior. Spine density and dendritic morphology were assessed using Golgi staining. Neurochemicals were quantified by microdialysis, doublecortin by immunofluorescence, and cAMP using an ELISA kit. Finally, the levels of cortical proteins of phosphorylated cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), postsynaptic density synapsin-1 and protein 95 (PSD95) were quantified by western blot. 16S rRNA gene sequencing was used to detect fecal microbiota.

Results

Treatment of CSDS-subjected mice with PLE (30.0–60.0 mg/kg,i.g.) enhanced sucrose preference, decreased immobility times in the TST and FST but did not affect locomotor activity. Furthermore, persistent social defeat stress decreased dendritic spine density and dendritic length in the brain, as well as decreased PSD95 and synapsin-1 expression. PLE, interestingly, inhibited dendritic spine loss and increased synaptic protein levels. PLE also increased brain levels of 5-HT, cAMP, phosphorylated (p)-CREB, BDNF, PSD95, and synapsin-1 in mice subjected to CSDS. Furthermore, PLE increased their doublecortin-positive cell count in the hippocampal dentate gyrus. CSDS mice represented a distinct fecal microbiota cluster which differed compared with normal C57BL/6J mice, and the phenotype was rescued by PLE.

Conclusions

PLE alleviated CSDS-induced depressive behaviors and spinal damage by suppressing serotonin reuptake and activating the cAMP/CREB/BDNF signaling pathway. Simultaneously, PLE influenced the composition of the fecal microbiota in CSDS-subjected mice.
Stage Ia squamous cell carcinoma as the malignant transformation of giant and unusual mature teratoma of the ovary in an elderly patient
Authors: Palomba Stefano , Russo Tiziana , Albonico Giuseppe , Tripodi Marcello
Published: June 2022

Background

Mature cystic teratomas of the ovary (MCTO) are a type of germ cell tumor that may contain well-differentiated tissues developed from three germ cell layers and constitute about 20% of ovarian germ cell tumors. They are rare ovarian tumors with an annual incidence variable from 1.2 to 14.2 cases per 100,000 that occur mainly in women of reproductive age. They are frequently benign with a slow growth rate, even if they can undergo a malignant transformation in about 1–2% of cases.

Case presentation

Here, we present the case of an elderly woman referred to gynecological first aid for acute abdominal pain and showing a giant and unusual MCTO at rapid growth with malignant transformation in squamous cell carcinoma (FIGO stage Ia). The patient underwent pelvic mass removal trough emergency longitudinal midline laparotomic incision with intraoperative frozen pathologic examination. A complete surgical staging during the first surgery was performed. After about 9 years of follow-up, she died of non-oncological reasons without recurrence.

Conclusions

Present case highlights that CMTO with malignant transformation should always be suspected in elderly women in presence of pelvic mass at rapid growth, even if in absence of other clinical and ultrasonographic signs of malignancy. An intraoperative frozen pathologic examination may drive the best treatment.
Initial experiences of prehospital blood product transfusions between 2016 and 2020 in Päijät-Häme hospital district, Finland
Authors: Yliharju Heidi , Jama Timo , Nordquist Hilla
Published: June 2022

Background

Treating hemorrhaging patients with prehospital blood product transfusions (PHBT) narrows transfusion delays and potentially benefits the patient. We describe our initial experiences of PHBT in a ground-based emergency medical service (EMS), where the transfusion protocol covers both traumatic and nontraumatic hemorrhaging patients.

Methods

A descriptive retrospective analysis was performed on the records of all the patients receiving red blood cells, freeze-dried plasma, or both during prehospital care from September 2016 to December 2020. The delays of PHBT and the effects on patients’ vital signs were analyzed and reported as the median and interquartile range (IQR) and analyzed using a Wilcoxon Signed rank test.

Results

65 patients received prehospital blood product transfusions (PHBT), 29 (45%) were non-traumatic, and 36 (55%) traumatic. The main two reasons for PHBT were blunt trauma (n = 30, 46%) and gastrointestinal hemorrhage (n = 20, 31%). The median time from the emergency call to the start of PHBT was 54 min (IQR 38), and the transfusion began on a median of 61 min (IQR 42) before arrival at the hospital. The median systolic blood pressure improved from a median 76.5 mmHg (IQR 36.5) before transfusion to a median of 116.60 mmHg (IQR 26.5) (p < 0.001) on arrival to the hospital. No transfusion-related severe adverse events were noted.

Conclusions

Starting PHBT in ground-based EMS is a feasible and viable option. The PHBT began significantly earlier than it would have started on arrival to the hospital, and it seems to be safe and improve patients’ physiology.

Study approval

D/2603/07.01.04.05/2019.
The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial
Authors: Askari Gholamreza , Sahebkar Amirhossein , Soleimani Davood , Mahdavi Atena , Rafiee Sahar , Majeed Muhammed , Khorvash Farzin , Iraj Bijan , Elyasi Mahshid , Rouhani Mohammad Hossein , Bagherniya Mohammad
Published: June 2022

Background

COVID-19 pandemic has made the disease a major global problem by creating a significant burden on health, economic, and social status. To date, there are no effective and approved medications for this disease. Curcumin as an anti-inflammatory agent can have a positive effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clinical symptoms, duration, severity, and inflammatory factors in patients with COVID-19.

Methods

Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days.

Results

Mean changes in complete blood count, liver enzymes, blood glucose levels, lipid parameters, kidney function, and c-reactive protein (CRP) were not significantly different between the two groups. There was a significant improvement in health status, including dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache, and dyspnea at week 2 in both curcumin-piperine and placebo groups (P value < 0.05); however, the improvement in weakness was more in the curcumin-piperine group than with placebo group (P value 025).

Conclusion

The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness. However, in this study, curcumin-piperine co-supplementation could not significantly affect the other indices, including biochemical and clinical indices.

Trial registration

Iranian Registry of Clinical Trials IRCT20121216011763N46. 2020-10-31
Prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO): study protocol for a randomized, controlled, outcome assessor-blinded trial
Authors: Schaller Stefan J. , Kiselev Jörn , Loidl Verena , Quentin Wilm , Schmidt Katrin , Mörgeli Rudolf , Rombey Tanja , Busse Reinhard , Mansmann Ulrich , Spies Claudia ,   on behalf of the PRAEP-GO consortium,, Spies Claudia , Marschall Ursula , Eckardt-Felmberg Rahel , Landgraf Irmgard , Schwantes Ulrich , Busse Reinhard , Mansmann Ulrich ,   PRAEP-GO investigators, Borchers Friedrich , Mörgeli Rudolf , Schönenberger Eva , Klassen Philipp , Kleikamp Bernadette , Brandhorst Philipp , Spiegel Anna-Lena H. , Papenfuß Bernhard , Dowideit Jens , Oefele Caroline , Gebhardt Volker , Zappel Kristina , Gövercin Mehmet , König Thomas , Chesi Claudio , Reißhauer Anett , Rosada Adrian , Müller-Werdan Ursula , Heymann Anja , Hanke Marion , Leymann Jens , Saller Thomas , Bischof Ann-Cathrin , Reisner Angelika , Albrecht Wolf Leopold , Wojciechowski Julia , Schuldt Martina , Baum Michael , Brnabic Dijana , von Pickardt Björn , Deutschmann Agnieszka , Scholz Carsten , May Lars , Eckardt-Felmberg Rahel , Wenghöfer Isabell , Blobner Manfred , Sattari Sima , Dummert Michael , Nau Carla , Otto Mareike , Voß-Lümers Ute , Lang Danny , Wiggert Daniel
Published: June 2022

Background

Frailty is expressed by a reduction in physical capacity, mobility, muscle strength, and endurance. (Pre-)frailty is present in up to 42% of the older surgical population, with an increased risk for peri- and postoperative complications. Consequently, these patients often suffer from a delayed or limited recovery, loss of autonomy and quality of life, and a decrease in functional and cognitive capacities. Since frailty is modifiable, prehabilitation may improve the physiological reserves of patients and reduce the care dependency 12 months after surgery.

Methods

Patients ≥ 70 years old scheduled for elective surgery or intervention will be recruited in this multicenter, randomized controlled study, with a target of 1400 participants with an allocation ratio of 1:1. The intervention consists of (1) a shared decision-making process with the patient, relatives, and an interdisciplinary and interprofessional team and (2) a 3-week multimodal, individualized prehabilitation program including exercise therapy, nutritional intervention, mobility or balance training, and psychosocial interventions and medical assessment. The frequency of the supervised prehabilitation is 5 times/week for 3 weeks. The primary endpoint is defined as the level of care dependency 12 months after surgery or intervention.

Discussion

Prehabilitation has been proven to be effective for different populations, including colorectal, transplant, and cardiac surgery patients. In contrast, evidence for prehabilitation in older, frail patients has not been clearly established. To the best of our knowledge, this is currently the largest prehabilitation study on older people with frailty undergoing general elective surgery.

Trial registration

ClinicalTrials.gov NCT04418271. Registered on 5 June 2020. Universal Trial Number (UTN): U1111-1253-4820
Testing a social network approach to promote HIV self-testing and linkage to care among fishermen at Lake Victoria: study protocol for the Owete cluster randomized controlled trial
Authors: Sheira Lila A. , Kwena Zachary A. , Charlebois Edwin D. , Agot Kawango , Ayieko Benard , Gandhi Monica , Bukusi Elizabeth A. , Thirumurthy Harsha , Camlin Carol S.
Published: June 2022

Background

Nearly 50% of men living with HIV in many countries are unaware of their HIV status; men also have lower uptake of HIV treatment and pre-exposure prophylaxis (PrEP). In SSA, highly mobile men such as those working in fishing communities alongside Lake Victoria have low uptake of HIV testing and low rates of linkage to HIV treatment and PrEP, despite increasing availability of these services. HIV self-testing (HIVST) kits hold promise for overcoming barriers to HIV testing and linkage to services for HIV-positive and HIV-negative men. We describe here a protocol for an HIV status-neutral, social network-based approach to promote HIV testing, linkage to care and prevention, and better health outcomes, including adherence, in fishermen around Lake Victoria.

Methods

Utilizing beach management unit (BMU) registries of fishermen operating in three Lake Victoria fishing communities in Siaya County, Kenya, we completed a census and social network mapping to identify close social networks of men. Network clusters identified by a socially-central lead (“promotor”) and selected to ensure maximal separation between treatment and control will be randomized. Promotors in both arms will receive basic HIV training; intervention promotors are further trained in HIVST to distribute kits to their cluster, while control promotors will distribute to their cluster vouchers for free HIVST at nearby clinics. We will test whether these promoters can enhance linkage to ART and PrEPafterself-testing, thereby addressing a key limitation of HIVST. We will also measure 6- and 12-month viral load in those living with HIV and PrEP adherence among those without HIV via urine tenofovir levels as objective markers of adherence.

Discussion

This study has the potential to improve HIV health and promote HIV prevention among a hard to reach, at-risk, and highly mobile population of men in Western Kenya—a critical population in Kenya’s HIV prevention and treatment program. Further, if successful, this innovative social networks-based model could be scaled at the regional level to address HIV prevention and care among similarly at-risk populations of men in eastern Africa and inland fisheries settings across the continent.

Trial registration

Self-Test Strategies and Linkage Incentives to Improve ART and PrEP Uptake in Men, registered on February 26, 2021, registration #NCT04772469.
Dominance of the zoonotic pathogen Cryptosporidium meleagridis in broiler chickens in Guangdong, China, reveals evidence of cross-transmission
Authors: Lin Xuhui , Xin Luyao , Qi Meng , Hou Minyu , Liao Shenquan , Qi Nanshan , Li Juan , Lv Minna , Cai Haiming , Hu Junjing , Zhang Jianfei , Ji Xiangbo , Sun Mingfei
Published: June 2022

Background

Cryptosporidium is one of the most prevalent parasites infecting both birds and mammals. To examine the prevalence of Cryptosporidium species and evaluate the public health significance of domestic chickens in Guangdong Province, southern China, we analyzed 1001 fecal samples from 43 intensive broiler chicken farms across six distinct geographical regions.

Methods

Individual DNA samples were subjected to nested PCR-based amplification and sequencing of the small subunit of the nuclear ribosomal RNA gene (SSU rRNA). Analysis of the 60 kDa glycoprotein gene (gp60) was performed to characterize the subtypes of C. meleagridis.

Results

The overall prevalence of Cryptosporidium was 13.2% (95% CI 11.1–15.3) (24 of 43 farms), with C. meleagridis (7.8%), C. baileyi (4.8%) and mixed infections (0.6%). Using the gp60 gene, three subtype families, IIIb, IIIe and IIIg, were identified, including six subtypes: one novel (IIIgA25G3R1a) and five previously reported (IIIbA23G1R1c, IIIbA24G1R1, IIIbA21G1R1a, IIIeA17G2R1 and IIIeA26G2R1). Within these subtypes, five known subtypes were genetically identical to those identified in humans.

Conclusions

This is the first report of C. meleagridis in chickens from Guangdong. The frequent occurrence of C. meleagridis in domestic chickens and the common C. meleagridis subtypes identified in both humans and chickens is of public health significance. Our study indicates that broiler chickens represent a potential zoonotic risk for the transmission of Cryptosporidium in this region.

Graphical Abstract
Plasmodium infection suppresses colon cancer growth by inhibiting proliferation and promoting apoptosis associated with disrupting mitochondrial biogenesis and mitophagy in mice
Authors: Yao Xin , Cao Yujie , Lu Li , Xu Yuanxia , Chen Hao , Liu Chuanqi , Chen Dianyi , Wang Kexue , Xu Jingxiang , Fang Runqi , Xia Hui , Li Jiangyan , Fang Qiang , Tao Zhiyong
Published: June 2022

Background

Colon cancer is a common gastrointestinal tumor with a poor prognosis, and thus new therapeutic strategies are urgently needed. The antitumor effect ofPlasmodiuminfection has been reported in some murine models, but it is not clear whether it has an anti-colon cancer effect. In this study, we investigated the anti-colon cancer effect ofPlasmodiuminfection and its related mechanisms using a mouse model of colon cancer.

Methods

An experimental model was established by intraperitoneal injection ofPlasmodium yoelii17XNL-infected erythrocytes into mice with colon cancer. The size of tumors was observed dynamically in mice, and the expression of Ki67 detected by immunohistochemistry was used to analyze tumor cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and the expression of apoptosis-related proteins including Bax, Bcl-2, caspase-9, and cleaved caspase-3 was detected by western blot and immunohistochemistry, respectively. Transmission electron microscopy (TEM) was used to observe the ultrastructural change in colon cancer cells, and the expression of mitochondrial biogenesis correlative central protein, PGC-1α, and mitophagy relevant crucial proteins, PINK1/Parkin, were detected by western blot.

Results

We found thatPlasmodiuminfection reduced the weight and size of tumors and decreased the expression of Ki67 in colon cancer-bearing mice. Furthermore,Plasmodiuminfection promoted mitochondria-mediated apoptosis in colon cancer cells, as evidenced by the increased proportion of TUNEL-positive cells, the upregulated expression of Bax, caspase-9, and cleaved caspase-3 proteins, and the downregulated expression of Bcl-2 protein. In colon cancer cells, we found destroyed cell nuclei, swollen mitochondria, missing cristae, and a decreased number of autolysosomes. In addition,Plasmodiuminfection disturbed mitochondrial biogenesis and mitophagy through the reduced expression of PGC-1α, PINK1, and Parkin proteins in colon cancer cells.

Conclusions

Plasmodiuminfection can play an anti-colon cancer role in mice by inhibiting proliferation and promoting mitochondria-mediated apoptosis in colon cancer cells, which may relate to mitochondrial biogenesis and mitophagy.

Graphical Abstract
Establishment of Wolbachia infection in Aedes aegypti from Pakistan via embryonic microinjection and semi-field evaluation of general fitness of resultant mosquito population
Authors: Sarwar Muhammad Sajjad , Jahan Nusrat , Ali Azeem , Yousaf Hafiz Kamran , Munzoor Iqra
Published: June 2022

Background

Dengue is a mosquito-borne viral disease that is mainly spread by Aedes aegypti. It is prevalent on five continents, predominantly in tropical and sub-tropical zones across the world. Wolbachia bacteria have been extensively used in vector control strategies worldwide. The focus of the current study was to obtain a natural population of Ae. aegypti harbouring Wolbachia and to determine the impact of this bacteria on the new host in a semi-field environment.

Methods

Wolbachia-infected Aedes albopictus was collected from the city of Lahore, Punjab, Pakistan, and Wolbachia were successfully introduced into laboratory-reared Ae. aegypti via embryonic microinjection. The stable vertical transmission of wAlbB in the host population was observed for eight generations, and the impact of Wolbachia on the general fitness of the host was evaluated in semi-field conditions.

Results

In the laboratory and semi-field experiments, wAlbB Wolbachia presented a strong cytoplasmic incompatibility (CI) effect, evidenced as zero egg hatching, in crosses between Wolbachia-infected males and wild (uninfected) females of Ae. aegypti. Wolbachia infection had no noticeable impact on the general fitness (P > 0.05), fecundity, body size (females and males) and mating competitiveness of the new host, Ae. aegypti. However, there was a significant decrease in female fertility (egg hatch) (P < 0.001). In addition, under starvation conditions, there was a remarkable decrease (P < 0.0001) in the life span of Wolbachia-infected females compared to uninfected females (4 vs. > 5 days, respectively).

Conclusions

Wolbachia strain wAlbB has a great potential to control the dengue vector in Ae. aegypti populations by producing 100% CI with a limited burden on its host in natural field conditions. This strain can be used as a biological tool against vector-borne diseases.

Graphical Abstract
Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
Authors: Hickson Jéssica , Athayde Lucas Felipe Almeida , Miranda Thainá Godinho , Junior Policarpo Ademar Sales , dos Santos Anderson Coqueiro , da Cunha Galvão Lúcia Maria , da Câmara Antônia Cláudia Jácome , Bartholomeu Daniella Castanheira , de Souza Rita de Cássia Moreira , Murta Silvane Maria Fonseca , Nahum Laila Alves
Published: June 2022

Background

Components of the antioxidant defense system in Trypanosoma cruzi are potential targets for new drug development. Superoxide dismutases (SODs) constitute key components of antioxidant defense systems, removing excess superoxide anions by converting them into oxygen and hydrogen peroxide. The main goal of the present study was to investigate the genes coding for iron superoxide dismutase (FeSOD) in T. cruzi strains from an evolutionary perspective.

Methods

In this study, molecular biology methods and phylogenetic studies were combined with drug assays. The FeSOD-A and FeSOD-B genes of 35 T. cruzi strains, belonging to six discrete typing units (Tcl–TcVI), from different hosts and geographical regions were amplified by PCR and sequenced using the Sanger method. Evolutionary trees were reconstructed based on Bayesian inference and maximum likelihood methods. Drugs that potentially interacted with T. cruzi FeSODs were identified and tested against the parasites.

Results

Our results suggest that T. cruzi FeSOD types are members of distinct families. Gene copies of FeSOD-A (n = 2), FeSOD-B (n = 4) and FeSOD-C (n = 4) were identified in the genome of the T. cruzi reference clone CL Brener. Phylogenetic inference supported the presence of two functional variants of each FeSOD type across the T. cruzi strains. Phylogenetic trees revealed a monophyletic group of FeSOD genes of T. cruzi TcIV strains in both distinct genes. Altogether, our results support the hypothesis that gene duplication followed by divergence shaped the evolution of T. cruzi FeSODs. Two drugs, mangafodipir and polaprezinc, that potentially interact with T. cruzi FeSODs were identified and tested in vitro against amastigotes and trypomastigotes: mangafodipir had a low trypanocidal effect and polaprezinc was inactive.

Conclusions

Our study contributes to a better understanding of the molecular biodiversity of T. cruzi FeSODs. Herein we provide a successful approach to the study of gene/protein families as potential drug targets.

Graphical Abstract